hiv monoclonal antibodies...25c2: human mab generated by electrofusion of pbl from hiv-1+ volunteers...
TRANSCRIPT
HIV
MonoclonalA
ntibodies
III-A-206
DE
C98
Table10: g
p41
MA
bID
LocationW
EA
US
equenceN
eutralizingIm
munogen
Species(Isotype)
6265F
3gp41(526-543
BH
10)gp41(15-33)
AA
GS
TM
GA
AS
MT
LTV
Q-
AR
QN
HIV
-1infection
human(IgG1
κ )
Donor:
H.K
atinger,Inst.A
ppl.M
icrobiol.,Vienna,A
ustriaR
eferences:[Buchacher
etal.(1994)]N
OT
ES
:•
5F3:
Hum
anM
Ab
generatedby
electrofusionof
PB
Lfrom
HIV
-1+volunteers
with
CB
-F7
cells[B
uchacheretal.(1994)]
62725C
2gp41(526-543
BH
10)gp41(15-33)
AA
GS
TM
GA
AS
MT
LTV
Q-
AR
QN
HIV
-1infection
human(IgG1
κ )
Donor:
H.K
atinger,Inst.A
ppl.M
icrobiol.,Vienna,A
ustriaand
ViralTesting
System
s,Houston,T
XR
eferences:[Buchacher
etal.(1992),Buchacher
etal.(1994),Sattentau
etal.(1995)]N
OT
ES
:•
25C2:
Hum
anM
Ab
generatedby
electrofusionofP
BL
fromH
IV-1+
volunteersw
ithC
B-F
7cells
–binds
oligomeric
andm
onomeric
gp41,andgp160
[Buchacher
etal.(1994)]•
25C2:
Called
IAM
41-25C2
–B
indingdom
ainoverlaps
sitesthat
arecriticalfor
gp120-gp41association
gStM
–binding
isenhanced
bysC
D4
–binding
regiondefined
as:gp41(21-38
BH
10)[S
attentauetal.(1995)]
62824G
3gp41(526-543
BH
10)gp41(15-33)
AA
GS
TM
GA
AS
MT
LTV
Q-
AR
QN
HIV
-1infection
human(IgG1
κ )
Donor:
H.K
atinger,Inst.A
ppl.M
icrobiol.,Vienna,A
ustriaR
eferences:[Buchacher
etal.(1992),Buchacher
etal.(1994)]N
OT
ES
:•
24G3:
Hum
anM
Ab
generatedby
electrofusionof
PB
Lfrom
HIV
-1+volunteers
with
CB
-F7
cells[B
uchacheretal.(1994)]
6291A
1gp41(526-543
BH
10)gp41(15-33)
AA
GS
TM
GA
AS
MT
LTV
Q-
AR
QN
HIV
-1infection
human(IgG1
κ )
Donor:
H.K
atinger,Inst.A
ppl.M
icrobiol.,Vienna,A
ustriaR
eferences:[Buchacher
etal.(1994)]N
OT
ES
:•
1A1:
Hum
anM
Ab
generatedusing
EB
Vtransform
ationofP
BL
fromH
IV-1+
volunteers[B
uchacheretal.(1994)]
630α
(566-586)gp41(566-586
BR
U)
gp41(51-71)A
HLLQ
LTV
WG
IKQ
LQ-
AR
ILH
IV-1
infectionhum
an
Donor:
H.K
atinger,Inst.A
ppl.M
icrobiol.,Vienna,A
ustriaR
eferences:[Poum
bouriosetal.(1992)]
HIV
MonoclonalA
ntibodies
III-A-207
DE
C98
MA
bID
LocationW
EA
US
equenceN
eutralizingIm
munogen
Species(Isotype)
631P
C5009
gp41(577-596B
RU
)gp41(62-81)
GIK
QLQ
AR
ILAVE
RY
LK-
DQ
Qrgp160
murine
Donor:
H.K
atinger,Inst.A
ppl.M
icrobiol.,Vienna,A
ustriaR
eferences:[Poum
bouriosetal.(1992)]
NO
TE
S:
•P
C5009:
Recognized
onlym
onomeric
gp41[P
oumbourios
etal.(1992)]
632polyclonalα
(577-596)gp41(577-596
BR
U)
gp41(62-81)G
IKQ
LQA
RILAV
ER
YLK
-D
HIV
-1infection
human
plasma
Donor:
H.K
atinger,Inst.A
ppl.M
icrobiol.,Vienna,A
ustriaR
eferences:[Poum
bouriosetal.(1992)]
NO
TE
S:
•α
(577-596):A
ffinitypurified
fromH
IV-1+
plasma
–preferentially
bindoligom
er[P
oumbourios
etal.(1992)]
633polyclonal
gp41(583-604)gp41(69-89)
RILAV
ER
YLK
DQ
QLLG
I-W
GC
SN
desialylatedH
IV-1
gp160rabbit
sera
Donor:
H.K
atinger,Inst.A
ppl.M
icrobiol.,Vienna,A
ustriaR
eferences:[Benjouad
etal.(1993)]N
OT
ES
:•
MA
bsraised
againstdesialylated
HIV
-1gp160
cross-reactw
ithH
IV-2
gp140due
toim
munodom
inantconserved
epitopein
gp41[B
enjouadetal.(1993)]
634polyclonal
gp41(584-602)gp41(70-87)
ILAVE
RY
LKD
LLGIW
GN
HIV
-1infection
human
seraD
onor:H
.Katinger,Inst.
Appl.
Microbiol.,V
ienna,Austria
References:[P
etrovetal.(1990)]
NO
TE
S:
•Im
munodom
inantandbroadly
reactivepeptide
[Petrov
etal.(1990)]
635V
10-9gp41(586-620
IIIB)
gp41(70-103)ILAV
ER
YLK
DQ
QLLG
IW-
GC
SG
KLIC
TTAV
PW
NA
SN
HIV
-1infection
human(IgG1
κ )
Donor:
H.K
atinger,Inst.A
ppl.M
icrobiol.,Vienna,A
ustriaR
eferences:[Robinson
Jr.etal.(1990a),R
obinsonJr.
etal.(1990b)]N
OT
ES
:•
V10-9:
Antibody
dependentenhancement(A
DE
)ofHIV
-1IIIB
infectivity,synergisticallyenhanced
byM
Ab
120-16[R
obinsonJr.
etal.(1990a)]•
V10-9:
Peptide
586-620blocks
complem
entmediated
AD
E[R
obinsonJr.
etal.(1990b)]
HIV
MonoclonalA
ntibodies
III-A-208
DE
C98
MA
bID
LocationW
EA
US
equenceN
eutralizingIm
munogen
Species(Isotype)
63686
gp41(586-620IIIB
)gp41(69-103)
RILAV
ER
YLK
DQ
QLLG
I-W
GC
SG
KLIC
TTAV
PW
NA
SN
HIV
-1infection
human(IgG1
κ )
Donor:
Evan
Hersh
andYoh-IchiM
atsumoto
References:[S
uganoet
al.(1988),R
obinsonJr.
etal.(1990a),
Robinson
Jr.et
al.(1990b),P
incuset
al.(1991),M
oranetal.(1993),W
isnewskietal.(1996),M
itchelletal.(1998)]N
OT
ES
:•
86:A
lsocalled
No.
86•
86:R
eactsw
ithgp41
andalso
reactedw
eaklyw
ithgp120
[Sugano
etal.(1988)]•
86:A
ntibodydependentenhancem
ent(AD
E)
ofHIV
-1IIIB
infectivityin
thepresence
ofcomplem
ent[Robinson
Jr.etal.(1990a)]
•86:
Peptide
586-620blocks
complem
entmediated
AD
E[R
obinsonJr.
etal.(1990b)]•
86:P
oorimm
unotoxinactivity
when
coupledto
RA
C–
peptidebinding
statedto
beaa
579-603[P
incusetal.(1991)]
•86:
Heavy
(VH
I)and
light(Vκ I)
chainsequenced
–enhancing
activity–
similar
germline
sequenceto
MA
bS
1-1,butvery
differentactivity[M
oranetal.(1993)]
•86:
86is
VH
1–
V-region
heavychain
usagew
asexam
inedand
abias
ofenhancedV
H1
andVH
4,andreduced
VH3,
was
notedam
ongH
IVinfected
individuals[W
isnewskietal.(1996)]
•86:
Mutations
inB
H10
gp160,W
596Yand
T605A
,as
wellas
deletionsof
605-609(T
TAVP
)and
597-609(G
CS
-G
KLIC
TTAV
P),abrogate
bindingofenhancing
MA
bs86,240D
,50-69,and246-D
–5/6
enhancingM
Abs
identifiedto
datebind
tothe
imm
unodominantregion
579-613[M
itchelletal.(1998)]•
86:N
IHA
IDS
Research
andR
eferenceR
eagentProgram
:380
637polyclonal
gp41(74-94?)
gp41E
RY
LKD
QLLG
IWG
CS
GK
-LIC
HIV
-1infection
human
sera
Donor:
Evan
Hersh
andYoh-IchiM
atsumoto
References:[S
hafferman
etal.(1989)]N
OT
ES
:•
Imm
unogenicdom
ainusefulfor
diagnostics[S
hafferman
etal.(1989)]
63841-6
gp41(598-609)gp41(88-94)
CS
GK
LICpeptide
LGLIW
GC
-S
GK
LIC(aa
598-609)
murine(IgG
2b )
Donor:
Evan
Hersh
andYoh-IchiM
atsumoto
References:[O
ldstoneetal.(1991)]
NO
TE
S:
•41-6:
Poor
cross-reactivityw
ithH
IV-2
peptideC
AF
RQ
VC
–slightly
more
reactivew
ithLG
LIWG
CS
GK
LICand
HIV
-2form
NS
WG
CA
FR
QV
C–
disulfidebond
between
cysteinesrequired
[Oldstone
etal.(1991)]
HIV
MonoclonalA
ntibodies
III-A-209
DE
C98
MA
bID
LocationW
EA
US
equenceN
eutralizingIm
munogen
Species(Isotype)
6394
gp41(598-609)gp41(88-94)
CS
GK
LICpeptide
LGLIW
GC
-S
GK
LIC(aa
598-609)
murine(IgG
2b )
Donor:
Evan
Hersh
andYoh-IchiM
atsumoto
References:[O
ldstoneetal.(1991)]
NO
TE
S:
•4:
There
isanother
MA
bw
iththis
IDthatreacts
with
integrase[O
ldstoneetal.(1991),B
izub-Bender
etal.(1994)]•
4:P
oorcross-reactivity
with
HIV
-2peptide
CA
FR
QV
C–
slightlym
orereactive
with
longerH
IV-2
peptideN
SW
G-
CA
FR
QV
C[O
ldstoneetal.(1991)]
64075
gp41(598-609)gp41(88-94)
CS
GK
LICpeptide
LGLIW
GC
-S
GK
LIC(aa
598-609)
rat(IgG)
Donor:
Evan
Hersh
andYoh-IchiM
atsumoto
References:[O
ldstoneetal.(1991)]
NO
TE
S:
•75:
Poor
cross-reactivityw
ithH
IV-2
peptideC
AF
RQ
VC
–m
orereactive
with
longerH
IV-2
peptideN
SW
G-
CA
FR
QV
C[O
ldstoneetal.(1991)]
64168.1
gp41(598-609)gp41(88-94)
CS
GK
LICpeptide
LGLIW
GC
-S
GK
LIC(aa
598-609)
murine(IgM
)
Donor:
Evan
Hersh
andYoh-IchiM
atsumoto
References:[O
ldstoneetal.(1991)]
NO
TE
S:
•68.1:
Cross-reactive
with
HIV
-2peptide
CA
FR
QV
C–
more
reactivew
ithlongerH
IV-1
peptideLG
LIWG
CS
GK
LICand
HIV
-2peptide
NS
WG
CA
FR
QV
C[O
ldstoneetal.(1991)]
64268.11
gp41(598-609)gp41(88-94)
CS
GK
LICpeptide
LGLIW
GC
-S
GK
LIC(aa
598-609)
murine(IgM
)
Donor:
Evan
Hersh
andYoh-IchiM
atsumoto
References:[O
ldstoneetal.(1991)]
NO
TE
S:
•68.11:
Cross-reactive
with
HIV
-2peptide
CA
FR
QV
C–
more
reactivew
ithlongerH
IV-1
peptideLG
LIWG
CS
GK
LICand
HIV
-2peptide
NS
WG
CA
FR
QV
C[O
ldstoneetal.(1991)]
HIV
MonoclonalA
ntibodies
III-A-210
DE
C98
MA
bID
LocationW
EA
US
equenceN
eutralizingIm
munogen
Species(Isotype)
643115.8
gp41(598-609)gp41(82-94)
LGLIW
GC
SG
KLIC
peptideLG
LIWG
C-
SG
KLIC
(aa598-
609)
murine(IgM
)
Donor:
Evan
Hersh
andYoh-IchiM
atsumoto
References:[O
ldstoneetal.(1991)]
NO
TE
S:
•115.8:
Poor
reactivityw
ithC
SG
KLIC
–reacts
well
with
longerH
IV-2
peptideN
SW
GC
AF
RQ
VC
asw
ellas
CA
FR
QV
C–
disulfidebond
between
cysteinesrequired
[Oldstone
etal.(1991)]
644M
-22gp41(598-609)
gp41(83-94)LG
IWG
CS
GK
LICH
IV-1
gp41peptide
(aa598-609)
murine(IgG
2b )
Donor:
?R
eferences:[Yam
adaetal.(1991)]
NO
TE
S:
•M
-22:S
trongestreactionof12
anti-HIV
-1gp41
MA
bsto
acellular43-kD
aprotein
foundin
ratandhum
anastrocytes
[Yam
adaetal.(1991)]
645M
-24gp41(598-609)
gp41(83-94)LG
IWG
CS
GK
LICH
IV-1
gp41peptide
(aa598-609)
murine(IgG
1 )
Donor:
?R
eferences:[Yam
adaetal.(1991)]
NO
TE
S:
•M
-24:S
tronglyreacted
with
acellular
43-kDa
proteinfound
inrat
andhum
anastrocytes
asw
ellas
with
gp41[Y
amada
etal.(1991)]
646M
-28gp41(598-609)
gp41(83-94)LG
IWG
CS
GK
LICH
IV-1
gp41peptide
(aa598-609)
murine(IgG
1 )
Donor:
?R
eferences:[Yam
adaetal.(1991)]
NO
TE
S:
•M
-28:S
tronglyreacted
with
acellular
43-kDa
proteinfound
inrat
andhum
anastrocytes
asw
ellas
with
gp41[Y
amada
etal.(1991)]
647M
-2gp41(598-609)
gp41(83-94)LG
IWG
CS
GK
LICH
IV-1
gp41peptide
(aa598-609)
murine(IgG
2b )
Donor:
?R
eferences:[Yam
adaetal.(1991)]
NO
TE
S:
•M
-2:S
tronglyreacted
with
acellular43-kD
aprotein
foundin
ratandhum
anastrocytes
asw
ellasw
ithgp41
[Yam
adaetal.(1991)]
HIV
MonoclonalA
ntibodies
III-A-211
DE
C98
MA
bID
LocationW
EA
US
equenceN
eutralizingIm
munogen
Species(Isotype)
648M
-11gp41(598-609)
gp41(83-94)LG
IWG
CS
GK
LICH
IV-1
gp41peptide
(aa598-609)
murine(IgG
1 )
Donor:
?R
eferences:[Yam
adaetal.(1991)]
NO
TE
S:
•M
-11:S
tronglyreacted
with
acellular
43-kDa
proteinfound
inrat
andhum
anastrocytes
asw
ellas
with
gp41[Y
amada
etal.(1991)]
649M
-13gp41(598-609)
gp41(83-94)LG
IWG
CS
GK
LICH
IV-1
gp41peptide
(aa598-609)
murine(IgG
2b )
Donor:
?R
eferences:[Yam
adaetal.(1991)]
NO
TE
S:
•M
-13:R
eactedw
itha
cellular43-kD
aprotein
foundin
ratand
human
astrocytesas
well
asw
ithgp41
[Yam
adaetal.(1991)]
650M
-25gp41(598-609)
gp41(83-94)LG
IWG
CS
GK
LICH
IV-1
gp41peptide
(aa598-609)
murine(IgG
1 )
Donor:
?R
eferences:[Yam
adaetal.(1991)]
NO
TE
S:
•M
-25:R
eactedw
itha
cellular43-kD
aprotein
foundin
ratand
human
astrocytesas
well
asw
ithgp41
[Yam
adaetal.(1991)]
651M
-1gp41(598-609)
gp41(83-94)LG
IWG
CS
GK
LICH
IV-1
gp41peptide
(aa598-609)
murine(IgG
1or2b )
Donor:
?R
eferences:[Yam
adaetal.(1991)]
NO
TE
S:
•M
-1:U
nlikeM
-22,didnotreactto
43-kDa
proteinfound
inratand
human
astrocytes[Y
amada
etal.(1991)]
652M
-4gp41(598-609)
gp41(83-94)LG
IWG
CS
GK
LICH
IV-1
gp41peptide
(aa598-609)
murine(IgG
2b )
Donor:
?R
eferences:[Yam
adaetal.(1991)]
NO
TE
S:
•M
-4:U
nlikeM
-22,didnotreactto
43-kDa
proteinfound
inratand
human
astrocytes[Y
amada
etal.(1991)]
HIV
MonoclonalA
ntibodies
III-A-212
DE
C98
MA
bID
LocationW
EA
US
equenceN
eutralizingIm
munogen
Species(Isotype)
653M
-6gp41(598-609)
gp41(83-94)LG
IWG
CS
GK
LICH
IV-1
gp41peptide
(aa598-609)
murine(IgG
2b )
Donor:
?R
eferences:[Yam
adaetal.(1991)]
NO
TE
S:
•M
-6:U
nlikeM
-22,didnotreactto
43-kDa
proteinfound
inratand
human
astrocytes[Y
amada
etal.(1991)]
654M
-29gp41(598-609)
gp41(83-94)LG
IWG
CS
GK
LICH
IV-1
gp41peptide
(aa598-609)
murine(IgG
1 )
Donor:
?R
eferences:[Yam
adaetal.(1991)]
NO
TE
S:
•M
-29:U
nlikeM
-22,didnotreactto
43-kDa
proteinfound
inratand
human
astrocytes[Y
amada
etal.(1991)]
655M
-36gp41(598-609)
gp41(83-94)LG
IWG
CS
GK
LICH
IV-1
gp41peptide
(aa598-609)
murine(IgG
1 )
Donor:
?R
eferences:[Yam
adaetal.(1991)]
NO
TE
S:
•M
-36:U
nlikeM
-22,didnotreactto
43-kDa
proteinfound
inratand
human
astrocytes[Y
amada
etal.(1991)]
6561B
8.envgp41(594-605
HX
B2)
gp41(84-94)G
IWG
CS
GK
LICN
HIV
-1infection
human(IgG
2λ )
Donor:
?R
eferences:[Banapour
etal.(1987)]N
OT
ES
:•
1B8.env:
Highly
conservedepitope
recognizedby
them
ajorityofH
IV-1
infectedpeople
[Banapour
etal.(1987)]
657polyclonalα
(598-609)gp41(598-609)
gp41(84-91)G
IWG
CS
GK
HIV
-1infection
human
Donor:
?R
eferences:[Poum
bouriosetal.(1992)]
NO
TE
S:
•α
(598-609):A
ffinitypurified
fromH
IV-1+
plasma
–im
munodom
inantregion,bindsoligom
erandm
onomer[P
oum-
bouriosetal.(1992)]
HIV
MonoclonalA
ntibodies
III-A-213
DE
C98
MA
bID
LocationW
EA
US
equenceN
eutralizingIm
munogen
Species(Isotype)
658clone
3gp41
gp41(87-96)G
CS
GK
LICT
TL
HIV
-1infection
human(IgG
1 )D
onor:?
References:[C
otropiaetal.(1992),C
otropiaetal.(1996)]
NO
TE
S:
•clone
3:C
orebinding
domain
gcsgkLIC–
lackofserologicalactivity
tothis
regioncorrelates
with
rapidprogression
ininfants
([Broliden
etal.(1989)])[C
otropiaetal.(1992)]
•clone
3:Inhibits
replicationofthree
diverseH
IV-1
laboratorystrains,as
wellas
anA
ZT-resistantisolate
[Cotropia
etal.(1996)]
659polyclonal
gp41(601-616)gp41(84-99)
GIW
GC
SG
KLIC
TTAV
PN
HIV
-1infection
human
seraD
onor:?
References:[P
etrovetal.(1990)]
NO
TE
S:
•Im
munodom
inantandbroadly
reactivepeptide
[Petrov
etal.(1990)]
66041-7
gp41(605-611)gp41(88-94)
CS
GK
LICN
HIV
-1infection
human(IgG
1κ )
Donor:
?R
eferences:[Bugge
etal.(1990)]N
OT
ES
:•
41-7:S
erafrom
6/6H
IV-1
positive,but
noH
IV-2
positive,individuals
interferedw
ith41-7
binding[B
uggeetal.(1990)]
6612A
2/26gp41(584-606
BR
U)
gp41(69-91)R
ILAVE
RY
LKD
LLGI-
WG
CS
GK
viralgp41m
urine(IgG)
Donor:
?R
eferences:[Poum
bouriosetal.(1992),P
oumbourios
etal.(1995)]N
OT
ES
:•
2A2/26:
Imm
unodominantregion,binds
botholigom
erand
monom
er[P
oumbourios
etal.(1992)]•
2A2/26:
∆550-561
(∆LLR
AIE
AQ
QH
LL),a
regionim
portantfor
oligomer
formation
diminishes
binding,∆
(550-561+
571-581)abrogates
binding[P
oumbourios
etal.(1995)]
HIV
MonoclonalA
ntibodies
III-A-214
DE
C98
MA
bID
LocationW
EA
US
equenceN
eutralizingIm
munogen
Species(Isotype)
66298-43
gp41(579-604H
XB
2)gp41(69-94)
RILAV
ER
YLK
DQ
QLLG
I-W
GC
SG
KLIC
NH
IV-1
infectionhum
an(IgG2κ )
Donor:
?R
eferences:[Pinter
etal.(1989),Gorny
etal.(1989),Tyleretal.(1990),X
uetal.(1991)]
NO
TE
S:
•98-43:
Reacts
equallyw
ellwith
oligomer
andm
onomer
[Pinter
etal.(1989)]•
98-43:P
oorA
DC
C(in
contrasttoM
Ab
120-16,gp41(644-663))[Tyler
etal.(1990)]•
98-43:579-604
bindsin
theim
munodom
inantregion[X
uetal.(1991)]
•98-43:
NIH
AID
SR
esearchand
Reference
ReagentP
rogram:
1241
663181-D
gp41(591-597H
XB
2)gp41(81-87)
QLLG
IWG
NH
IV-1
infectionhum
an(IgG2κ )
Donor:
?R
eferences:[Xu
etal.(1991),Robinson
Jr.etal.(1991),E
ddlestonetal.(1993),F
orthaletal.(1995),Fontenotetal.(1995)]
NO
TE
S:
•181-D
:Fine
mapping
indicatescore
isLLG
IW[X
uetal.(1991)]
•181-D
:No
enhancingor
neutralizationactivity
[Robinson
Jr.etal.(1991)]
•181-D
:Called
SZ
-181.D[E
ddlestonetal.(1993)]
•181-D
:No
neutralizing,noA
DC
C,and
noviralenhancing
activity[F
orthaletal.(1995)]
664240-D
gp41(592-600H
XB
2)gp41(82-90)
LLGIW
GC
SG
NH
IV-1
infectionhum
an(IgG1κ )
Donor:
?R
eferences:[Xu
etal.(1991),Robinson
Jr.etal.(1991),S
pearetal.(1993),B
inleyetal.(1996),W
isnewskietal.(1995),
Wisnew
skietal.(1996),Mitchelletal.(1998)]
NO
TE
S:
•240-D
:Fine
mapping
indicatescore
isIW
G[X
uetal.(1991)]
•240-D
:No
neutralizingactivity,som
eenhancing
activity[R
obinsonJr.
etal.(1991)]•
240-D:D
idnotm
ediatedeposition
ofcomplem
entcomponentC
3on
HIV
infectedcells
[Spear
etal.(1993)]•
240-D:B
indsto
alinear
epitopelocated
inthe
Cluster
Iregion–
bindingof50-69
and240-D
inhibitedby
Fabs
A1,
A4,M
8B,M
26B,M
12Band
T2
[Binley
etal.(1996)]•
240-D:
Called
F240:
F240
inVH
3–
V-region
heavychain
usagew
asexam
inedand
abias
ofenhanced
VH
1and
VH
4,andreduced
VH3,w
asnoted
among
HIV
infectedindividuals
[Wisnew
skietal.(1996)]•
240-D:
Mutations
inB
H10
gp160,W
596Yand
T605A
,as
well
asdeletions
of605-609
(TTAV
P)
and597-609
(GC
SG
KLIC
TTAV
P),
abrogatebinding
ofenhancing
MA
bs86,
240D,
50-69,and
246-D–
5/6enhancing
MA
bsidentified
todate
bindto
theim
munodom
inantregion579-613
[Mitchelletal.(1998)]
•240-D
:NIH
AID
SR
esearchand
Reference
ReagentP
rogram:
1242
HIV
MonoclonalA
ntibodies
III-A-215
DE
C98
MA
bID
LocationW
EA
US
equenceN
eutralizingIm
munogen
Species(Isotype)
665D
61gp41(592-608
HX
B2)
gp41(82-98)LLG
IWG
CS
GK
LICT
TA
Vdim
ericE
nvm
urineD
onor:?
References:[E
arletal.(1994),Richardson
Jretal.(1996),W
eissenhornetal.(1996),E
arletal.(1997)]N
OT
ES
:•
D61:
Lineargp41epitope
inthe
clusterIregion–
human
serablocked
bindingin
oligomeric
ELIS
Aassay
toa
similar
extentforgp41
MA
bsD
20,D43,D
61,andT
4[R
ichardsonJr
etal.(1996)]•
D61:
Does
notprecipitate
gp41(21-166),but
dueto
astructuraldifference
inthe
disulfidebonding
regionnear
thetw
ocysteines
–the
authorspropose
thatthisregion
may
changeconform
ationduring
theactivation
ofthem
embrane
fusionstate
oftheH
IV-1
glycoprotein[W
eissenhornetal.(1996)]
•D
61:B
indingm
apsto
region597-613:
WG
CS
GK
LICT
TAVP
WN
A–
imm
unodominantregion
containingtw
oC
ysresidues
–this
antibody,alongw
ithhum
anM
Ab
246-D,can
beblocked
byany
ofagroup
of8conform
ationalMA
bs(M
10,D41,D
54,T4,T
6,T9,T
10and
T35)
–m
embers
ofthiscom
petitiongroup
areblocked
bysera
fromH
IV-1+
individuals[E
arletal.(1997)]
666D
49gp41(597-613)
gp41(82-98)LLG
IWG
CS
GK
LICT
TA
Vdim
ericE
nvm
urineD
onor:?
References:[E
arletal.(1994),Earletal.(1997)]
NO
TE
S:
•D
49:B
indingm
apsto
region597-613:
WG
CS
GK
LICT
TAVP
WN
A–
imm
unodominantregion
containingtw
oC
ysresidues
[Earletal.(1997)]
667T
32gp41(597-613)
gp41(82-98)LLG
IWG
CS
GK
LICT
TA
Vtetram
ericE
nvm
urineD
onor:?
References:[E
arletal.(1994),Earletal.(1997)]
NO
TE
S:
•T
32:B
indingm
apsto
region597-613:
WG
CS
GK
LICT
TAVP
WN
A–
imm
unodominantregion
containingtw
oC
ysresidues
[Earletal.(1997)]
668T
34gp41(597-613)
gp41(82-98)LLG
IWG
CS
GK
LICT
TA
Vtetram
ericE
nvm
urineD
onor:?
References:[E
arletal.(1994),Earletal.(1997)]
NO
TE
S:
•T
34:B
indingm
apsto
region597-613:
WG
CS
GK
LICT
TAVP
WN
A–
imm
unodominantregion
containingtw
oC
ysresidues
[Earletal.(1997)]
HIV
MonoclonalA
ntibodies
III-A-216
DE
C98
MA
bID
LocationW
EA
US
equenceN
eutralizingIm
munogen
Species(Isotype)
669246-D
gp41(579-604H
XB
2)gp41(80-87)
LLGIW
GN
HIV
-1infection
human(IgG
1κ )
Donor:
Susan
Zolla-P
azner,NY
UM
edC
enter,NY,N
YR
eferences:[Xu
etal.(1991),Robinson
Jr.etal.(1991),S
pearetal.(1993),E
ddlestonetal.(1993),F
orthaletal.(1995),M
ancaetal.(1995),S
aarloosetal.(1995),E
arletal.(1997)]N
OT
ES
:•
246-D:F
inem
appingindicates
coreis
LLGI[X
uetal.(1991)]
•246-D
:Did
notmediate
depositionofcom
plementcom
ponentC3
onH
IVinfected
cellsunless
cellsw
erepre-incubated
with
sCD
4[S
pearetal.(1993)]
•246-D
:No
neutralizingactivity,som
eenhancing
activity[R
obinsonJr.
etal.(1991)]•
246-D:C
alledS
Z-246.D
[Eddleston
etal.(1993)]•
246-D:N
oneutralizing
activity,bothA
DC
Cand
viralenhancingactivity
[Forthaletal.(1995)]
•246-D
:Virions
complexed
togp41
Ab
facilitatepresentation
ofp66R
Tepitopes
toT
hcells
[Manca
etal.(1995)]•
246-D:
Ab-m
ediatedactivation
ofcom
plement
onH
IV+
cellsis
higherthan
Ab
independentactivation
–w
hathas
beenterm
ed“A
bindependent”
infact
resultsin
partfrom
IgMin
normalhum
anserum
thatis
HIV
-cross-reactive[S
aarloosetal.(1995)]
•246-D
:M
utationsin
BH
10gp160,
W596Y
andT
605A,
asw
ellas
deletionsof
605-609(T
TAVP
)and
597-609(G
CS
GK
LICT
TAVP
),abrogate
bindingof
enhancingM
Abs
86,240D
,50-69,
and246-D
–5/6
enhancingM
Abs
identifiedto
datebind
tothe
imm
unodominantregion
579-613[M
itchelletal.(1998)]•
246-D:
This
antibody,along
with
murine
MA
bD
61,can
beblocked
byany
ofa
groupof
8conform
ationalMA
bs(M
10,D41,D
54,T4,T
6,T9,T
10and
T35)
[Earletal.(1997)]
•246-D
:NIH
AID
SR
esearchand
Reference
ReagentP
rogram:
1245
6702F
11gp41(H
XB
2)gp41(79-90)
DQ
QLLG
IWG
CS
GN
HIV
-1infection
human(IgG
1 )D
onor:?
References:[E
atonetal.(1994)]
NO
TE
S:
•2F
11:E
nhancesinfectivity
evenin
theabsence
ofcomplem
ent–does
notmediate
AD
CC
orneutralize
virus[E
atonetal.(1994)]
6711H
5gp41(579-613
BH
10)gp41(68-102)
AR
ILAVE
RY
LKD
LLG-
IWG
CS
GK
LICT
TAVP
WN
AN
HIV
-1infection
human(IgG1
κ )
Donor:
?R
eferences:[Buchacher
etal.(1992),Buchacher
etal.(1994)]N
OT
ES
:•
1H5:
Generated
byelectrofusion
ofPB
Lfrom
HIV
-1positive
volunteersw
ithC
B-F
7cells
[Buchacher
etal.(1994)]
HIV
MonoclonalA
ntibodies
III-A-217
DE
C98
MA
bID
LocationW
EA
US
equenceN
eutralizingIm
munogen
Species(Isotype)
6721F
11gp41(579-613
BH
10)gp41(68-102)
AR
ILAVE
RY
LKD
LLG-
IWG
CS
GK
LICT
TAVP
WN
AN
HIV
-1infection
human(IgG1
κ )
Donor:
H.K
atinger,Inst.A
ppl.M
icrobiol.,Vienna,A
ustriaR
eferences:[Buchacher
etal.(1992),Buchacher
etal.(1994)]N
OT
ES
:•
1F11:
Generated
byelectrofusion
ofPB
Lfrom
HIV
-1positive
volunteersw
ithC
B-F
7cells
[Buchacher
etal.(1994)]
6734D
4gp41(579-613
BH
10)gp41(68-102)
AR
ILAVE
RY
LKD
LLG-
IWG
CS
GK
LICT
TAVP
WN
AN
HIV
-1infection
human(IgG1
λ )
Donor:
H.K
atinger,Inst.A
ppl.M
icrobiol.,Vienna,A
ustriaand
ViralTesting
System
s,Houston,T
XR
eferences:[Buchacher
etal.(1992),Buchacher
etal.(1994),Chen
etal.(1994b),Sattentau
etal.(1995)]N
OT
ES
:•
4D4:
Generated
byelectrofusion
ofPB
Lfrom
HIV
-1positive
volunteersw
ithC
B-F
7cells
[Buchacher
etal.(1994)]
6743D
9gp41(579-613
BH
10)gp41(68-102)
AR
ILAVE
RY
LKD
LLG-
IWG
CS
GK
LICT
TAVP
WN
AN
HIV
-1infection
human(IgG1
κ )
Donor:
H.K
atinger,Inst.A
ppl.M
icrobiol.,Vienna,A
ustriaR
eferences:[Buchacher
etal.(1992),Buchacher
etal.(1994)]N
OT
ES
:•
3D9:
Generated
byelectrofusion
ofPB
Lfrom
HIV
-1positive
volunteersw
ithC
B-F
7cells
[Buchacher
etal.(1994)]
6754G
2gp41(579-613
BH
10)gp41(68-102)
AR
ILAVE
RY
LKD
LLG-
IWG
CS
GK
LICT
TAVP
WN
AN
HIV
-1infection
human(IgG1
κ )
Donor:
H.K
atinger,Inst.A
ppl.M
icrobiol.,Vienna,A
ustriaR
eferences:[Buchacher
etal.(1992),Buchacher
etal.(1994)]N
OT
ES
:•
4G2:
Generated
byelectrofusion
ofPB
Lfrom
HIV
-1positive
volunteersw
ithC
B-F
7cells
[Buchacher
etal.(1994)]
6764B
3gp41(579-613
BH
10)gp41(68-102)
AR
ILAVE
RY
LKD
LLG-
IWG
CS
GK
LICT
TAVP
WN
AN
HIV
-1infection
human(IgG1
λ )
Donor:
H.K
atinger,Inst.A
ppl.M
icrobiol.,Vienna,A
ustriaR
eferences:[Buchacher
etal.(1992),Buchacher
etal.(1994),Chen
etal.(1994b)]N
OT
ES
:•
4B3:
Generated
byelectrofusion
ofPB
Lfrom
HIV
-1positive
volunteersw
ithC
B-F
7cells
[Buchacher
etal.(1994)]
HIV
MonoclonalA
ntibodies
III-A-218
DE
C98
MA
bID
LocationW
EA
US
equenceN
eutralizingIm
munogen
Species(Isotype)
67750-69
gp41(579-603B
H10)
gp41(69-93)R
ILAVE
RY
LKD
LLGI-
WG
CS
GK
LIN
HIV
-1infection
human(IgG2
κ )
Donor:
Susan
Zolla-P
azner,NY
U,N
YR
eferences:[Tilletal.(1989),P
interetal.(1989),Gorny
etal.(1989),Xu
etal.(1991),Robinson
Jr.etal.(1991),S
attentau&
Moore(1991),
Eddleston
etal.(1993),
Spear
etal.(1993),
Laaletal.(1994),
Chen
etal.(1995),
Sattentau
etal.(1995),
Manca
etal.(1995),
McD
ougalet
al.(1996),P
oignardet
al.(1996a),B
inleyet
al.(1996),K
lasse&
Sattentau(1996),
Stam
atatosetal.(1997),B
ootsetal.(1997),M
itchelletal.(1998)]N
OT
ES
:•
50-69:C
ombined
with
deglycosylatedA
chainofricin
istoxic
tolines
ofHIV
-infectedT
cells(H
9)and
monocytes
(U937)
[Tilletal.(1989)]
•50-69:
Reacts
preferentiallyw
ithgp160
oligomer,com
paredto
gp41m
onomer
[Pinter
etal.(1989)]•
50-69:K
illsH
IV-infected
cellsw
hencoupled
todeglycosylated
ricinA
chain[G
ornyetal.(1989)]
•50-69:
The
epitopeis
affectedby
theconform
ationconferred
bythe
two
cysteinesatam
inoacids
598and
604[X
uetal.(1991)]
•50-69:
Enhances
HIV
-1infection
invitro
–synergizes
with
huMA
b120-16
invitro
toenhance
HIV
-1infection
tolevelapproaching
thatfoundin
polyclonalanti-HIV
serum[R
obinsonJr.
etal.(1991)]•
50-69:Tw
ofold
increasein
bindingto
gp120in
thepresence
ofboundsC
D4
[Sattentau
&M
oore(1991)]•
50-69:C
alledS
Z-50.69
–binds
toan
epitopew
ithinaa
579-613[E
ddlestonetal.(1993)]
•50-69:
Did
notmediate
depositionofcom
plementcom
ponentC3
onH
IVinfected
cellsunless
cellsw
erepre-incubated
with
sCD
4–
complem
entmediated
virolysisofM
Nand
IIIBin
thepresence
ofsCD
4[S
pearetal.(1993)]
•50-69:
Epitope
describedas
ClusterI,601-604,conform
ational–does
notneutralizeIIIB
orsynergizeneutralization
byanti-V
3M
Ab
447-52Dor
byC
D4
BS
MA
bs[Laaletal.(1994)]
•50-69:
One
ofseveral
anti-gp41M
Abs
thatbind
toa
gp41-maltose
bindingfusion
proteindesigned
tostudy
theleucine
zipperdom
ainofgp41,show
ingthatthe
constructhasretained
aspectsofnorm
algp41conform
ation[C
henetal.(1995)]
•50-69:
Preferentially
bindsoligom
er–
bindingincreased
afterpretreatm
entof
infectedcells
with
sCD
4–
bindingdom
ainoverlaps
sitethatis
criticalforgp120-gp41
association,avE
ry[S
attentauetal.(1995)]
•50-69:
Virions
complexed
togp41
Ab
facilitatepresentation
ofp66R
Tepitopes
toT
hcells
[Manca
etal.(1995)]•
50-69:D
oesnotneutralize
HIV
-1LA
I[McD
ougaletal.(1996)]•
50-69:P
rebindingofanti-V
3,and
CD
4iMA
bs48d
and17b,
butnotanti-V2
neutralizingM
Abs,
exposethe
50-69epitope
[Poignard
etal.(1996a)]•
50-69:B
indsto
alinear
epitopelocated
inthe
Cluster
Iregion–
bindingof50-69
and240-D
inhibitedby
Fabs
A1,
A4,M
8B,M
26B,M
12Band
T2
[Binley
etal.(1996)]•
50-69:U
sedto
testexposureofgp41
uponsC
D4
binding[K
lasse&
Sattentau(1996)]
•50-69:
Binding
ofanti-gp120M
Abs
IgG1b12
or654-30Ddoes
notmediate
significantexposureofthe
gp41epitopes
forM
Abs
2F5
and50-69
[Stam
atatosetal.(1997)]
HIV
MonoclonalA
ntibodies
III-A-219
DE
C98
677cont.
•50-69:
Abs
thatrecognize
discontinuousepitopes
canidentify
mim
otopesfrom
aphage
peptidedisplay
library–
50-69m
apsto
anim
munodom
inantdom
ainin
gp41–
threegroups
ofpeptides
were
selected,one
which
seems
most
closelyrelated
togp41
sequencepeptide
consensusis
WG
Cxx(R
K)(x
n )LxC–
theanalogous
gp41sequence
WG
CS
GK
LICis
presentinm
ostMgroup
clades,exceptDw
itha
comm
onL
toH
substitution[B
ootsetal.(1997)]
•50-69:
Mutations
inB
H10
gp160,W
596Yand
T605A
,as
well
asdeletions
of605-609
(TTAV
P)
and597-609
(GC
SG
KLIC
TTAV
P),
abrogatebinding
ofenhancing
MA
bs86,
240D,
50-69,and
246-D–
5/6enhancing
MA
bsidentified
todate
bindto
theim
munodom
inantregion579-613
–identifies
non-contiguousW
596-G597-C
598...C604-
T605
asm
inimalepitope
[Mitchelletal.(1998)]
•50-69:
NIH
AID
SR
esearchand
Reference
ReagentP
rogram:
531
MA
bID
LocationW
EA
US
equenceN
eutralizingIm
munogen
Species(Isotype)
678F
abA
1gp41(584-609
LAI)
gp41(69-98)R
ILAVE
RY
LKD
LLGI-
WG
CS
GK
LICT
TAVN
HIV
-1infection
human(IgG1
κ )
Donor:
Susan
Zolla-P
azner,NY
U,N
YR
eferences:[Binley
etal.(1996)]N
OT
ES
:•
Fab
A1:
Binds
toC
lusterI
region–
competes
with
MA
bs240-D
and50-69
–conform
ationsensitive
–variable
regionssequenced
[Binley
etal.(1996)]
679F
abA
4gp41(584-609
LAI)
gp41(69-98)R
ILAVE
RY
LKD
LLGI-
WG
CS
GK
LICT
TAVN
HIV
-1infection
human(IgG1
κ )
Donor:
Susan
Zolla-P
azner,NY
U,N
YR
eferences:[Binley
etal.(1996)]N
OT
ES
:•
Fab
A4:
Binds
toC
lusterI
region–
competes
with
MA
bs240-D
and50-69
–conform
ationsensitive
–variable
regionssequenced
[Binley
etal.(1996)]
680F
abM
8Bgp41(584-609
LAI)
gp41(69-98)R
ILAVE
RY
LKD
LLGI-
WG
CS
GK
LICT
TAVN
HIV
-1infection
human(IgG1
κ )
Donor:
Susan
Zolla-P
azner,NY
U,N
YR
eferences:[Binley
etal.(1996)]N
OT
ES
:•
Fab
M8B
:B
indsto
Cluster
Iregion
–com
petesw
ithM
Abs
240-Dand
50-69–
conformation
sensitive–
variableregions
sequenced[B
inleyetal.(1996)]
HIV
MonoclonalA
ntibodies
III-A-220
DE
C98
MA
bID
LocationW
EA
US
equenceN
eutralizingIm
munogen
Species(Isotype)
681F
abM
26Bgp41(584-609
LAI)
gp41(69-98)R
ILAVE
RY
LKD
LLGI-
WG
CS
GK
LICT
TAVN
HIV
-1infection
human(IgG1
κ )
Donor:
Susan
Zolla-P
azner,NY
U,N
YR
eferences:[Binley
etal.(1996)]N
OT
ES
:•
Fab
M26B
:B
indsto
Cluster
Iregion
–com
petesw
ithM
Abs
240-Dand
50-69–
conformation
sensitive–
variableregions
sequenced[B
inleyetal.(1996)]
682F
abT
2gp41(584-609
LAI)
gp41(69-98)R
ILAVE
RY
LKD
LLGI-
WG
CS
GK
LICT
TAVN
HIV
-1infection
human(IgG1
κ )
Donor:
Susan
Zolla-P
azner,NY
U,N
YR
eferences:[Binley
etal.(1996)]N
OT
ES
:•
Fab
T2:
Binds
toC
lusterI
region–
competes
with
MA
bs240-D
and50-69
–conform
ationsensitive
–variable
regionssequenced
[Binley
etal.(1996)]
683F
abM
12Bgp41(584-609
LAI)
gp41(69-98)R
ILAVE
RY
LKD
LLGI-
WG
CS
GK
LICT
TAVN
HIV
-1infection
human(IgG1
κ )
Donor:
Susan
Zolla-P
azner,NY
U,N
YR
eferences:[Binley
etal.(1996)]N
OT
ES
:•
Fab
M12B
:B
indsto
Cluster
Iregion
–com
petesw
ithM
Abs
240-Dand
50-69–
conformation
sensitive–
variableregions
sequenced[B
inleyetal.(1996)]
68441.4
gp41(584-609)gp41(69-98)
RILAV
ER
YLK
DQ
QLLG
I-W
GC
SG
KLIC
TTAV
Donor:
JanM
cClure,B
ristol-Myers
Squibb
Pharm
aceuticalRes
Inst,Seattle,W
AR
eferences:[Pincus
&M
cClure(1993)]
NO
TE
S:
•41.4:
Binds
topeptide
weakly,butto
gp160w
ithhigher
affinitythan
41.1,andcross-com
petesw
ith41.1
–probably
conformational–
MA
bw
ascoupled
toricin
Achain
(RA
C)
–sC
D4
enhancesthe
efficacyofim
munotoxins
invitro
30-fold[P
incus&
McC
lure(1993)]
HIV
MonoclonalA
ntibodies
III-A-221
DE
C98
MA
bID
LocationW
EA
US
equenceN
eutralizingIm
munogen
Species(Isotype)
68541-1
gp41(584-609)gp41(69-98)
RILAV
ER
YLK
DQ
QLLG
I-W
GC
SG
KLIC
TTAV
gp160m
urine(IgG1κ )
Donor:
JanM
cClure,B
ristol-Myers
Squibb
Pharm
aceuticalRes
Inst,Seattle,W
AR
eferences:[Gosting
etal.(1987),Dalgleish
etal.(1988),Pincus
etal.(1991),Pincus
&M
cClure(1993),M
anietal.(1994),P
incusetal.(1996),P
incusetal.(1998)]
NO
TE
S:
•41-1:
This
antibodygp41(584-609)
[Manietal.(1994)]seem
sto
havebeen
named
thesam
eas
adifferentM
Ab
togp41(735-752
IIIB)
[Dalgleish
etal.(1988)]•
41-1:A
lsocalled
41.1,although
possiblynot,
theliterature
isconfusing
becausetw
ogp41
MA
bsthat
bindto
thisregion
with
similar
names
(dashversus
period)are
listedas
murine
andhum
an•
41-1:B
roadlyreactive
[Gosting
etal.(1987)]•
41-1:T
hisantibody
seems
tohave
beennam
edthe
same
asa
differentMA
bto
gp41(735-752)[Dalgleish
etal.(1988)]•
41-1:E
fficaciousas
anim
munotoxin
when
coupledto
RA
C–
gavelinear
epitopeas
gp160579-603
[Pincus
etal.(1991)]•
41-1:C
alled41.1,
anddescribed
asa
human
MA
b–
cross-competes
with
41.4–
sCD
4enhances
theefficacy
ofim
munotoxins
invitro
30-fold–
MA
bw
ascoupled
toricin
Achain
(RA
C)
–[P
incus&
McC
lure(1993)]•
41-1:D
idnot
requirethe
C-C
disulfidebridge
andloop
formation,
canbind
simultaneously
with
9-11[M
anietal.(1994)]
•41-1:
Called
41.1,and
describedas
ahum
anM
Ab,
binding579-60
4–
apanel
ofim
munotoxins
was
generatedby
linkingE
nvM
Abs
toricin
A–
imm
unotoxinsm
ediatedcellkilling,
butkilling
was
notdirectly
proportionaltobinding
[Pincus
etal.(1996)]
6869-11
gp41(584-609)gp41(69-94)
RILAV
ER
YLK
DQ
QLLG
I-W
GC
SG
KLIC
gp160m
urine(IgG1 )
Donor:
JanM
cClure,B
ristol-Myers
Squibb
Pharm
aceuticalRes
Inst,Seattle,W
AR
eferences:[Manietal.(1994)]
NO
TE
S:
•9-11:
requiredthe
C-C
disulfidebridge
andloop
formation,can
bindsim
ultaneouslyw
ith41-1
[Manietal.(1994)]
687polyclonal
gp41(589-596)gp41
(72-79)AV
ER
YLK
DH
IV-1
infectionhum
ansera
Donor:
JanM
cClure,B
ristol-Myers
Squibb
Pharm
aceuticalRes
Inst,Seattle,W
AR
eferences:[Klasse
etal.(1991)]N
OT
ES
:•
Substitutions
anddeletions
inpeptide
583-599w
eresystem
aticallystudied
–alterations
inAV
ER
YLK
Dabrogated
theantigenicity
ofpeptidesw
ithm
ostof14hum
ansera
[Klasse
etal.(1991)]
HIV
MonoclonalA
ntibodies
III-A-222
DE
C98
MA
bID
LocationW
EA
US
equenceN
eutralizingIm
munogen
Species(Isotype)
688polyclonal
gp41(583-599)gp41
(66-82)LQ
AR
ILAVE
RY
LKD
LH
IV-1
infectionhum
ansera
Donor:
JanM
cClure,B
ristol-Myers
Squibb
Pharm
aceuticalRes
Inst,Seattle,W
AR
eferences:[Klasse
etal.(1993b)]N
OT
ES
:•
42H
IV-1
positivehum
ansera
were
testedagainstW
Tpeptide,and
peptidew
ithsubstitution
589A
toT
:11/42reacted
stronglyw
ithW
T,weakly
with
A589T
–31
reactedw
eaklyw
ithparental,even
more
weakly
with
substituted[K
lasseetal.(1993b)]
6899G
5Agp41(596-599
IIIB)
gp41(81-84)
QLLG
Anti-idiotype
againstM
38m
urine(IgM)
Donor:
JanM
cClure,B
ristol-Myers
Squibb
Pharm
aceuticalRes
Inst,Seattle,W
AR
eferences:[Lopalcoetal.(1993),B
eretta&
Dalgleish(1994)]
NO
TE
S:
•9G
5A:A
nti-idiotypeto
gp120C
terminus
(C5
region)M
Ab
M38
[Lopalcoetal.(1993)]
6903D
6gp41(604-617
BH
10)gp41(89-103)
SG
KLIC
TTAV
PW
NA
SH
IV-1
infectionhum
an(IgG1κ )
Donor:
H.K
atinger,Inst.A
ppl.M
icrobiol.,Vienna,A
ustriaand
ViralTesting
System
s,Houston,T
XR
eferences:[Felgenhaueretal.(1990),H
eetal.(1992),C
henetal.(1994b),S
attentauetal.(1995),W
isnewskietal.(1996)]
NO
TE
S:
•3D
6:S
equenceofcD
NA
encodingV
-regions
[Felgenhauer
etal.(1990)]•
3D6:
Fab
fragmentcrystalstructure
[He
etal.(1992)]•
3D6:
This
MA
bbinds
toH
IVgp41,and
toa
43kd
proteinfound
inhum
anT,B
andm
onocytecelllines,proposed
molecular
mim
icry[C
henetal.(1994b)]
•3D
6:C
alledIA
M41-3D
6:binding
increasedafter
pretreatment
ofinfected
cellsw
ithsC
D4
–binding
domain
overlapssite
thatiscriticalfor
gp120-gp41association,ctta
V[S
attentauetal.(1995)]
•3D
6:3D
6is
VH
3–
V-region
heavychain
usagew
asexam
inedand
abias
ofenhancedV
H1
andVH
4,andreduced
VH
3,was
notedam
ongH
IVinfected
individuals[W
isnewskietal.(1996)]
HIV
MonoclonalA
ntibodies
III-A-223
DE
C98
MA
bID
LocationW
EA
US
equenceN
eutralizingIm
munogen
Species(Isotype)
691120-16
gp41(644-663H
XB
2)gp41(134-153)
SLIE
ES
QN
EK
NE
QE
L-LE
LN
HIV
-1infection
human(IgG2
κ )
Donor:
H.K
atinger,Inst.A
ppl.M
icrobiol.,Vienna,A
ustriaand
ViralTesting
System
s,Houston,T
XR
eferences:[Andris
etal.(1992),Robinson
Jr.etal.(1990a),Tyleretal.(1990),X
uetal.(1991),R
obinsonJr.
etal.(1991),E
ddlestonetal.(1993),F
orthaletal.(1995),Wisnew
skietal.(1996)]N
OT
ES
:•
120-16:A
lsocalled
SZ
-120.16•
120-16:A
ntibodydependentenhancem
ent(AD
E)ofH
IV-1
IIIBinfectivity,synergistically
enhancedby
MA
bV
10-9[R
obinsonJr.
etal.(1990a)]•
120-16:P
otentAD
CC
(incontrastto
MA
b98-43,gp41(579-604))
[Tyleretal.(1990)]
•120-16:
Lessreactive
regionthan
AVE
RY
region–
mostA
bsinvolving
thisregion
boundconform
ationalepitopes,this
was
theonly
linearone
[Xu
etal.(1991)]•
120-16:S
ynergizesw
ithhuM
Ab
50-69in
vitroto
enhanceH
IV-1
infection[R
obinsonJr.
etal.(1991)]•
120-16:C
alledS
Z-120.16
[Eddleston
etal.(1993)]•
120-16:N
oneutralizing
activity,bothA
DC
Cand
viralenhancingactivity
[Forthaletal.(1995)]
•120-16:
120-16is
VH4
–V
-regionheavy
chainusage
was
examined
anda
biasof
enhancedV
H1
andVH
4,and
reducedVH
3,was
notedam
ongH
IVinfected
individuals[W
isnewskietal.(1996)]
692D
50gp41(642-665)
gp41(132-155)D
ISC
ON
TIN
UO
US
dimeric
Env
murine
Donor:
H.K
atinger,Inst.A
ppl.M
icrobiol.,Vienna,A
ustriaand
ViralTesting
System
s,Houston,T
XR
eferences:[Earletal.(1994),B
inleyetal.(1996),R
ichardsonJr
etal.(1996),Earletal.(1997)]
NO
TE
S:
•D
50:T
houghtto
bea
discontinuousepitope
recognizingresidues
between
649-668–
designatedcluster
II–
Fabs
D5,D
11,G1,T
3,M12,M
15,S6,S
8,S9,S
10block
binding[B
inleyetal.(1996)]
•D
50:R
ichardsonsuggests
thisis
alinear
gp41epitope
[Richardson
Jretal.(1996)]
•D
50:F
oundto
bindto
alinear
peptide,betw
eenenv
amino
acids642-655
–can
beblocked
bythe
conformation
dependentMA
bsD
16,D17,D
31,D36,D
37,D40,D
44,D55,D
59,T37,and
T45
–the
regionis
inthe
imm
unogeniccluster
two
region–
reactivew
ith9/10
HIV
-1strains
tested,allexceptHIV
-1A
DA
,inw
hichthe
changeE
659Dand
E662A
may
resultinthe
lossofbinding
(ELLE
toD
LLA)
[Earletal.(1997)]
HIV
MonoclonalA
ntibodies
III-A-224
DE
C98
MA
bID
LocationW
EA
US
equenceN
eutralizingIm
munogen
Species(Isotype)
69398-6
gp41(644-663H
XB
2)gp41(134-153)
SLIE
ES
QN
EK
NE
QE
L-LE
LN
HIV
-1infection
human(IgG2
κ )
Donor:
H.K
atinger,Inst.A
ppl.M
icrobiol.,Vienna,A
ustriaand
ViralTesting
System
s,Houston,T
XR
eferences:[Pinter
etal.(1989),
Gorny
etal.(1989),
Till
etal.(1989),
Robinson
Jr.et
al.(1990a),Tyler
etal.(1990),
Andris
etal.(1992),Sattentau
&M
oore(1991),Robinson
Jr.etal.(1991),X
uetal.(1991),E
ddlestonetal.(1993),S
pearet
al.(1993),Taniet
al.(1994),Laalet
al.(1994),C
henet
al.(1995),F
orthaletal.(1995),
Manca
etal.(1995),
Sattentau
etal.(1995),Wisnew
skietal.(1996)]N
OT
ES
:•
98-6:R
eactspreferentially
with
gp160oligom
er,compared
togp41
monom
er[P
interetal.(1989)]
•98-6:
Kills
HIV
-infectedcells
when
coupledto
deglycosylatedricin
Achain
[Gorny
etal.(1989)]•
98-6:Toxic
toH
IV-infected
Tcells
(H9)
andm
onocytes(U
937)w
hencoupled
todeglycosylated
Achain
ofricin
[Tilletal.(1989)]
•98-6:
No
neutralizingor
enhancingactivity
forH
IV-1
IIIB[R
obinsonJr.
etal.(1990a)]•
98-6:S
ervesas
targetforantibody-dependentcellular
cytotoxicity,AD
CC
[Tyleretal.(1990)]
•98-6:
Two
foldincrease
inbinding
togp120
inthe
presenceofbound
sCD
4[S
attentau&
Moore(1991)]
•98-6:
No
neutralizingor
enhancingactivity
[Robinson
Jr.etal.(1991)]
•98-6:
Appeared
tobe
specificfor
aconform
ationalordiscontinuous
epitope[X
uetal.(1991)]
•98-6:
Called
SZ
-98.6–
bindsto
aconform
ationaldomain
within
aa644-663
ofgp41,andreacts
with
astrocytes,asdo
167-7and
ND
-15G1
[Eddleston
etal.(1993)]•
98-6:D
idnotm
ediatedeposition
ofcomplem
entcomponentC
3on
HIV
infectedcells,binding
enhancedby
sCD
4[S
pearetal.(1993)]
•98-6:
This
MA
bw
asexpressed
asa
surfaceanti-gp41
monoclonalantibody
receptorfor
gp41on
aC
D4-negative
B-cellline.
Transfected
cellscould
bindH
IVenvelope,
butcould
notbe
infectedby
HIV
-1.W
henC
D4
deliveredby
retroviralconstructs
was
expressedon
thesecells,
theyacquired
theability
toreplicate
HIV
-1,and
sIg/gp41specifically
enhancedviralreplication
[Tanietal.(1994)]•
98-6:E
pitopedescribed
asC
lusterII,644-663,conformational–
doesnotneutralize
IIIBorsynergize
neutralizationby
anti-V3
MA
b447-52D
orby
CD
4B
SM
Abs
[Laaletal.(1994)]•
98-6:O
neof
severalanti-gp41
MA
bsthat
bindto
agp41-m
altosebinding
fusionprotein
designedto
studythe
leucinezipper
domain
ofgp41,showing
thattheconstructhas
retainedaspects
ofnormalgp41
conformation
[Chen
etal.(1995)]•
98-6:N
oneutralizing
activity,positiveA
DC
Cactivity,and
noviralenhancing
activity[F
orthaletal.(1995)]•
98-6:V
irionscom
plexedto
gp41A
bfacilitate
presentationofp66
RT
epitopesto
Th
cells[M
ancaetal.(1995)]
•98-6:
Preferentially
recognizesoligom
ericform
ofgp41
–enhanced
bindingto
HIV
-1infected
cellsat
37degrees
relativeto
4degrees
–addition
ofsCD
4enhances
binding[S
attentauetal.(1995)]
•98-6:
98-6is
VH4
–V
-regionheavy
chainusage
was
examined
anda
biasofenhanced
VH
1and
VH
4,andreduced
VH
3,was
notedam
ongH
IVinfected
individuals[W
isnewskietal.(1996)]
•98-6:
NIH
AID
SR
esearchand
Reference
ReagentP
rogram:
1240
HIV
MonoclonalA
ntibodies
III-A-225
DE
C98
MA
bID
LocationW
EA
US
equenceN
eutralizingIm
munogen
Species(Isotype)
694167-7
gp41(644-663)gp41(134-153)
SLIE
ES
QN
EK
NE
QE
L-LE
LH
IV-1
infectionhum
an(IgG2λ )
Donor:
H.K
atinger,Inst.A
ppl.M
icrobiol.,Vienna,A
ustriaand
ViralTesting
System
s,Houston,T
XR
eferences:[Xu
etal.(1991),Eddleston
etal.(1993)]N
OT
ES
:•
167-7:S
pecificfor
aconform
ationalepitope[X
uetal.(1991)]
•167-7:
Called
SZ
-167.7–
bindsto
aconform
ationaldomain
within
aa644-663
ofgp41,andreacts
with
astrocytes,as
do98-6
andN
D-15G
1[E
ddlestonetal.(1993)]
695N
D-15G
1gp41(644-663
HX
B2)
gp41(134-153)S
LIEE
SQ
NQ
QE
KN
EQ
EL-
LEL
HIV
-1infection
human(IgG1
κ )
Donor:
?R
eferences:[Eddleston
etal.(1993)]N
OT
ES
:•
ND
-15G1:
Mapped
tothe
conformational
epitopew
ithinaa
644-663,and
reactsw
ithastrocytes,
asdo
98-6and
167-7[E
ddlestonetal.(1993)]
696167-D
gp41(644-663H
XB
2)gp41(134-153)
SLIE
ES
QN
EK
NE
QE
L-LE
LN
HIV
-1infection
human(IgG1
λ )
Donor:
?R
eferences:[Spear
etal.(1993),Forthaletal.(1995),M
ancaetal.(1995)]
NO
TE
S:
•167-D
:D
idnot
mediate
depositionof
complem
entcom
ponentC
3on
HIV
infectedcells
–com
plement
mediated
virolysisofM
Nand
IIIBin
thepresence
ofsCD
4[S
pearetal.(1993)]
•167-D
:No
neutralizingactivity,no
AD
CC
activity,andno
viralenhancingactivity
[Forthaletal.(1995)]
•167-D
:Virions
complexed
togp41
Ab
facilitatepresentation
ofp66R
Tepitopes
toT
hcells
[Manca
etal.(1995)]
HIV
MonoclonalA
ntibodies
III-A-226
DE
C98
MA
bID
LocationW
EA
US
equenceN
eutralizingIm
munogen
Species(Isotype)
6972F
5gp41(662-667
BH
10)gp41(152-157)
ELD
KW
AL
PH
IV-1
infectionhum
an(IgG3κ )
Donor:
Herm
annK
atinger,U
.of
Bodenkultur,
orP
olymun
Scientific
Inc.,V
ienna,A
ustria;V
iralTesting
System
s,H
ouston,TX
,US
AR
eferences:[Buchacheretal.(1992),M
usteretal.(1993),Allaw
ayetal.(1993),K
lasseetal.(1993a),P
urtscheretal.(1994),Laaletal.(1994),B
uchacheretal.(1994),D’S
ouzaetal.(1994),C
onleyetal.(1994b),T
halietal.(1994),Chen
etal.(1994b),M
usteret
al.(1994),B
eretta&
Dalgleish(1994),
D’S
ouzaet
al.(1995),T
rkolaet
al.(1995),S
attentauet
al.(1995),M
oore&
Ho(1995),
Neurath
etal.(1995),
Kessler
2ndet
al.(1995),C
alarotaet
al.(1996),M
cKeating(1996),
Poignard
etal.(1996b),
Sattentau(1996),
Conley
etal.(1996),
Pincus
etal.(1996),
McK
eatinget
al.(1996),S
toiberet
al.(1996),P
urtscheretal.(1996),Schutten
etal.(1997),D’S
ouzaetal.(1997),M
oetal.(1997),Lietal.(1997),K
esslerIIetal.(1997),M
oore&
Trkola(1997),M
ascolaetal.(1997),S
tamatatos
etal.(1997),Turbica
etal.(1997),Ugolinietal.(1997),B
urton&
Montefiori(1997),E
arletal.(1997),Andrus
etal.(1998),Mondor
etal.(1998),Connor
etal.(1998),Yang
etal.(1998),T
rkolaetal.(1998),F
outsetal.(1998),E
rnstetal.(1998),Takefman
etal.(1998),Lietal.(1998)]N
OT
ES
:•
2F5:
Also
calledIA
M2F
5,IAM
-41-2F5,IA
M2F
5•
2F5:
DK
WA
definedas
thecore
sequence–
highlyconserved
epitopeneutralizing
MA
b[B
uchacheret
al.(1992),M
usteretal.(1993)]
•2F
5:S
ynergyw
ithcom
binationsofC
D4-based
molecules
ininhibition
ofHIV
-1E
nvm
ediatedcellfusion
[Allaw
ayetal.(1993)]
•2F
5:C
alledIA
M-41-2F
5–
reportsM
Ab
tobe
IgG1 –the
gp41m
utation582(A
lato
Thr)
resultsin
conformational
changesin
gp120thatconfer
neutralizationresistance
toconform
ationallysensitive
neutralizingM
Abs
–neutraliza-
tionefficiency
of2F5
isnotaffected
[Klasse
etal.(1993a)]•
2F5:
Broadly
reactiveneutralizing
activity,E
LDK
WA
isrelatively
conserved–
neutralized2
primary
isolates[P
urtscheretal.(1994)]
•2F
5:F
ailedto
showsynergy
with
anti-CD
4binding
siteIIIB
neutralizingantibodies
[Laaletal.(1994)]•
2F5:
MA
bgenerated
byelectrofusion
ofP
BL
fromH
IV-1
positivevolunteers
with
CB
-F7
cells[B
uchacheretal.(1994)]
•2F
5:Included
ina
multi-lab
studyfor
antibodycharacterization
bindingand
neutralizationassay
comparison
[D’S
ouzaetal.(1994)]
•2F
5:C
alledIA
M-41-2F
5–
neutralizedlab
andprim
aryisolates
–t
1/2
dissociation122
min
forthe
peptide,and156
min
forgp41
–core
D(K
/R)W
–A
bresistantisolate
hadthe
sequenceK
LDN
WA
[Conley
etal.(1994b)]•
2F5:
gp41m
utation(582
A/T
)thatreducesneutralization
ofanti-CD
4binding
siteM
Abs
doesnotalter2F
5’sability
toneutralize
[Thalietal.(1994)]
•2F
5:2F
5epitope
ELD
KW
Ainserted
intoan
imm
unogenicloop
ininfluenza
virushem
agglutinincan
elicitIIIB,M
Nand
RF
neutralizingsera
inim
munized
mice
[Muster
etal.(1994)]•
2F5:
Found
toneutralize
MN
,JRC
SF,and
two
Bsubtype
primary
isolates,butnota
Dsubtype
primary
isolate,bym
ostlabsin
am
ulti-laboratorystudy
involving11
labs[D
’Souza
etal.(1995)]•
2F5:
Cross-clade
primary
virusneutralizing
activity–
LDK
Wdefined
asthe
coreepitope
[Trkola
etal.(1995)]
HIV
MonoclonalA
ntibodies
III-A-227
DE
C98
697cont.
•2F
5:C
alledIA
M41-2F
5–
exposedin
thepresence
ofgp120
onthe
cellsurface,w
hilem
ostof
gp41is
masked
–binds
proximalto
transmem
braneregion
[Sattentau
etal.(1995)]•
2F5:
Review
:binds
tothe
onlygenerally
acceptedstrong
neutralizingepitope
outsideofgp120,one
ofonly3
MA
bsw
ithstrong
broadactivity
againstprim
aryviruses,
theothers
are2G
12and
IgG1b12
–unique
mem
berof
epitopecluster
[Moore
&H
o(1995)]andJohn
Moore,per
comm
1996•
2F5:
MA
bbinding
decreasesthe
accessibilityor
altersthe
conformation
ofthe
gp41fusion
domain
andof
gp120dom
ains,includingthe
bindingsite
forthe
CD
4cellreceptor
[Neurath
etal.(1995)]•
2F5:
Broad
cross-cladeneutralization
ofprimary
isolates–
additiveneutralization
incom
binationw
ithanti-C
D4B
SM
Ab
IgG1b12
(Called
BM
12)[K
essler2nd
etal.(1995)]•
2F5:
Only
4/20A
rgentinianand
3/43S
wedish
HIV
+sera
reactedw
ithLLE
LDK
WA
SL
–sera
reactingw
ithpeptides
thatcontainedE
LDK
WA
tendedto
havehigh
neutralizationtiters
–the
regioncarboxylterm
inaltoE
DLK
WA
was
foundto
bem
oreim
portantfor
polyclonalseraA
Bbinding,
670-675W
NW
FD
I–
2F5
boundm
oststrongly
tothe
peptideQ
ELLE
LDK
WA
[Calarota
etal.(1996)]•
2F5:
ELD
KW
AS
isin
agp41
bindingregion
forthe
negativeregulator
ofcom
plement
factorH
(CF
H)
–A
bsto
HIV
generallydo
notcauseefficientcom
plement-m
ediatedlysis,butbinding
of2F5
caninterfere
with
CH
Fbinding,
facilitatingH
IVdestruction
bycom
plement[S
toiberetal.(1996)]
•2F
5:P
rimary
isolatesfrom
cladeA
,B
,and
Eare
neutralizedby
2F5
–neutralization
requiresthe
LDK
Wm
otif–
neutralizationresistantisolates
or2F
5selected
variantsallhad
substitutionsin
theD
orK
[Purtscher
etal.(1996)]•
2F5:
Neutralizes
HX
B2,
primary
isolates,and
chimeric
virusw
ithgp120
fromprim
aryisolates
inan
HX
B2
back-ground
[McK
eatingetal.(1996)]
•2F
5:R
eview:
oneofthree
MA
bs(IgG
1b12,2G12,and
2F5)generally
acceptedas
havingsignificantpotency
againstprim
aryisolates
[Poignard
etal.(1996b)]•
2F5:
Review
:only
fourepitopes
havebeen
describedw
hichcan
stimulate
auseful
neutralizingresponse
toa
broadspectrum
ofprimary
isolates,represented
bythe
bindingsites
ofMA
bs:447-52-D
,2G12,
Fab
b12,and
2F5
[Sattentau(1996)]
•2F
5:2F
5w
asinfused
intotw
ochim
panzeesw
hichw
erethen
givenan
intravenouschallenge
with
aprim
aryH
IV-1
isolate–
bothbecam
einfected,butw
ithdelayed
detectionand
prolongeddecrease
inviralload
relativeto
controls,indicating
thatpreexisting,
neutralizingantibodies
(passivelyadm
inisteredor
activelyelicited)
affectthe
courseof
acute-phasevirus
replicationand
canbe
influentialaftertheA
bcan
nolongerbe
detectedin
theperipheralcirculation
[Conley
etal.(1996)]•
2F5:
Apanelofim
munotoxins
were
generatedby
linkingE
nvM
Abs
torici
nA
–im
munotoxins
mediated
cellkilling,butkilling
was
notdirectlyproportionalto
binding[P
incusetal.(1996)]
•2F
5:C
alledIA
M2F
5–
antibodym
ediatedenhancem
entor
inhibitionseem
edto
bedeterm
inedby
isolaterather
thanantibody
specificity–
inthis
study,only
2F5
inhibitedthe
entryofallthe
virusesstudied,
irrespectiveoftheir
phenotype,anddirectly
proportionaltoits
affinityto
monom
ericH
IV-1
gp160[S
chuttenetal.(1997)]
•2F
5:O
fthreeneutralizing
MA
bs(257-D
,IgG1b12,and
2F5),2F
5w
asthe
onlyone
toinhibitthe
entryofallviruses
studied,bothS
IandN
SI,w
itha
potencyproportionalto
itsaffinity
form
onomeric
gp126[S
chuttenetal.(1997)]
HIV
MonoclonalA
ntibodies
III-A-228
DE
C98
697cont.
•2F
5:In
am
ultilabevaluation
ofmonoclonalantibodies,only
IgG1b12,2G
12,and2F
5could
neutralizeatleasthalf
ofthe9
primary
testisolatesata
concentrationof
<25µ
gper
mlfor
90%viralinhibition
–the
isolatesw
ithno
2F5
neutralizingsusceptibility
hadthe
sequencesA
LGQ
WA
orE
LDT
WA
insteadof
ED
LKW
A–
7/9prim
aryisolates
were
neutralized,andA
LDK
WQ
andA
LDK
WA
were
susceptibleto
neutralization[D
’Souza
etal.(1997)]•
2F5:
AJR
CS
Fvariant
thatw
asselected
forIgG
1b12resistance
remained
sensitiveto
MA
bs2G
12and
2F5,
forcom
binationtherapy
[Mo
etal.(1997)]•
2F5:
One
of14
human
MA
bstested
forability
toneutralize
achim
ericS
HIV
-vpu+,
which
expressedH
IV-1
IIIBenv
–strong
neutralizerof
SH
IV-vpu+
–all
Ab
combinations
testedshow
edsynergistic
neutralization–
2F5
hassynergistic
responsew
ithM
Abs
694/98-D(anti-V
3),2G12,b12,and
F105
[Lietal.(1997)]•
2F5:
IgG1b12
was
more
potentw
ithgreater
breadththan
MA
b2F
5in
aninfection
reductionassay
including35
primary
isolates[K
esslerIIetal.(1997)]
•2F
5:R
eview:
MA
Bs
2F5,
2G12
andIgG
1b12have
potentialfor
usein
combination
with
CD
4-IgG2
asan
im-
munotherapeutic
orim
munoprophylactic
–hom
ologousM
Abs
tothese
arerare
inhum
ansand
vaccinestrategies
shouldconsider
includingconstructs
thatmay
enhanceexposure
oftheseM
Abs’epitopes
[Moore
&T
rkola(1997)]•
2F5:
Binding
ofanti-gp120M
Abs
IgG1b12
or654-30D
doesnotm
ediatesignificantexposure
ofthegp41
epitopesfor
MA
bs2F
5and
50-69[S
tamatatos
etal.(1997)]•
2F5:
Using
concentrationsofA
bsachievable
invivo,the
triplecom
binationof2F
5,2G12
andH
IVIG
was
foundto
besynergistic
tohave
thegreatestbreadth
andm
agnitudeofresponse
against15clade
Bprim
aryisolates
[Mascola
etal.(1997)]•
2F5:
Used
tostandardize
polyclonalresponseto
CD
4B
S[T
urbicaetal.(1997)]
•2F
5:T
heonly
MA
boutofa
largepanelto
showno
correlationbetw
eenV
iralbindinginhibition
andneutralization
[Ugolinietal.(1997)]
•2F
5:T
hisreview
summ
arizesresults
about2F
5:it
bindsextracellularly,
nearthe
transmem
branedom
ain,it
isthe
onlygp41
MA
bthatis
neutralizing,itreacts
with
many
non-Bclade
virusesand
hasa
paradoxicallyw
eakbinding
tovirus,given
theneutralizing
titres[B
urton&
Montefiori(1997)]
•2F
5:P
ost-exposureprophylaxis
was
effectivew
henM
Ab
694/98-Dw
asdelivered
15m
inpost-exposure
toH
IV-1
LAI
inhu-P
BL-S
CID
mice,
butdeclined
to50%
ifdelivered
60m
inpost-exposure,
andsim
ilartim
econstraints
havebeen
observedfor
HIV
IG,2F
5and
2G12,in
contrasttoM
Ab
BAT
123thatcould
protectdelivered4
hourspost
infection[A
ndrusetal.(1998)]
•2F
5:T
hisM
Ab
andthe
resultsof
[Ugoliniet
al.(1997)]are
discussed–
theauthors
proposethat
anA
bbound
togp41
would
typicallyprojectless
fromthe
surfaceofthe
virionand
sobe
unableto
interferew
ithattachm
ent[Parren
etal.(1998)]•
2F5:
Ab
fromgp120
vaccinatedindividuals
priorto
infection,w
hosubsequently
became
HIV
infected,could
notachieve
90%neutralization
ofthe
primary
virusby
which
theindividuals
were
ultimately
infected–
theseviruses
were
notparticularly
refractiveto
neutralization,as
determined
bytheir
susceptibilityto
neutralizationby
MA
bs2G
12,IgG1b12,2F
5and
447-52D[C
onnoretal.(1998)]
HIV
MonoclonalA
ntibodies
III-A-229
DE
C98
697cont.
•2F
5:A
neutralizationassay
was
developedbased
onhem
inestedP
CR
amplification
ofthe
LTR
(HN
PC
R)
–LT
R-
HN
PC
Rconsistently
revealedH
IVD
NA
andw
asshow
nto
bea
rapid,specificand
reliableneutralization
assaybased
ontests
with
6M
Abs
and5
isolates[Y
angetal.(1998)]
•2F
5:A
wide
rangeofneutralizing
titersw
asobserved
thatwas
independentofco-receptorusage–
2F5
was
them
ostpotentofthe
MA
bstested
[Trkola
etal.(1998)]•
2F5:
Points
outthat
2G12
and2F
5,potent
neutralizingantibodies,
were
identifiedby
screeningfor
cellsurface
(oligomeric
envelope)reactivity
[Fouts
etal.(1998)]•
2F5:
The
ELD
KW
Aepitope
was
insertedinto
theantigenic
siteB
ofinfluenza
hemagglutinin
andexpressed
onbaculovirus
infectedinsect
cells,flanked
by3
additionalrandomam
inoacids,
xELD
KW
Axx
–FA
CS
was
usedto
isolatethe
clonethat
displayedthe
epitopew
iththe
most
markedly
increasedbinding
capacityfor
2F5,
toidentify
particularlyspecific
imm
unogenicconstructs
–P
ELD
KW
AP
Pw
asa
highaffinity
formselected
byFA
CS
[Ernst
etal.(1998)]•
2F5:
Inducescom
plement-m
ediatedlysis
inM
Nbut
notprim
aryisolates
–prim
aryisolates
arerefractive
toC
ML
[Takefman
etal.(1998)]•
2F5:
Neutralization
synergyw
asobserved
when
theM
Abs
694/98-D(V
3),2F5
(gp41),and2G
12(gp120
discontin-uous)
were
usedin
combination,and
evengreater
neutralizingpotentialw
asseen
with
theaddition
ofafourth
MA
b,F
105(C
D4
BS
)[Lietal.(1998)]
•2F
5:U
KM
edicalResearch
CouncilA
IDS
reagent:A
RP
3063•
2F5:
NIH
AID
SR
esearchand
Reference
ReagentP
rogram:
1475
HIV
MonoclonalA
ntibodies
III-A-230
DE
C98
MA
bID
LocationW
EA
US
equenceN
eutralizingIm
munogen
Species(Isotype)
698polyclonal
gp41(662-667B
H10)
gp41(152-157)E
LDK
WA
Lchim
ericinfluenza
virus/ELD
KW
Am
urine(IgG,IgA
)
Donor:
Herm
annK
atinger,U
.of
Bodenkultur,
orP
olymun
Scientific
Inc.,V
ienna,A
ustria;V
iralTesting
System
s,H
ouston,TX
,US
AR
eferences:[Muster
etal.(1994),Muster
etal.(1995)]N
OT
ES
:•
Sustained
ELD
KW
Aspecific
IgAresponse
inm
ucosaofim
munized
mice
[Muster
etal.(1995)]
699B
30gp41(720-734
BH
10)gp41(210-224)
HLP
IPR
GP
DR
PE
GIE
mis-folded
LAI
rgp160m
urine(IgG1 )
Donor:
Gearoge
Lewis
References:[A
baciogluetal.(1994)]
NO
TE
S:
•B
30:E
pitopeboundaries
mapped
bypeptide
scanning[A
baciogluetal.(1994)]
700B
31gp41(727-734
BH
10)gp41(217-224)
PD
RP
EG
IEm
is-foldedLA
Irgp160
murine(IgG
1 )
Donor:
Gearoge
Lewis
References:[A
baciogluetal.(1994)]
NO
TE
S:
•B
31:E
pitopeboundaries
mapped
bypeptide
scanning[A
baciogluetal.(1994)]
701B
33gp41(727-734
BH
10)gp41(217-224)
PD
RP
EG
IEN
Baculovirus-
expressedm
is-folded
rgp160IIIB
:NL43,
MicroG
enSys
murine(IgG
1 )
Donor:
Gearoge
Lewis
References:[A
baciogluetal.(1994),B
ristowetal.(1994)]
NO
TE
S:
•B
33:T
hereare
two
MA
bsin
theliterature
named
B33.
See
alsogp120,LA
I123-142[B
ristowetal.(1994)]
•B
33:E
pitopeboundaries
mapped
bypeptide
scanningIgG
1[A
baciogluetal.(1994)]
HIV
MonoclonalA
ntibodies
III-A-231
DE
C98
MA
bID
LocationW
EA
US
equenceN
eutralizingIm
munogen
Species(Isotype)
702C
8gp41(727-732
BH
10)gp41(217-222)
PD
RP
EG
Nm
is-foldedLA
Irgp160
murine(IgG
1 )
Donor:
Gearoge
Lewis
References:[P
incus&
McC
lure(1993),Pincus
etal.(1993),Abacioglu
etal.(1994)]N
OT
ES
:•
C8:
Imm
unotoxinof
C8
coupledto
ricin-Adoes
notm
ediatecells
killing,and
isnot
affectedby
sCD
4[P
incus&
McC
lure(1993)]•
C8:
Ab
responsein
IIIBlab
workers
was
compared
togp160
LAI
vaccinerecipients
–C
8w
asused
asa
control–the
dominantresponse
among
vaccineesw
asto
thism
id-gp41region,butnotam
ongthe
infectedlab
workers
–A
bsbinding
thisregion
donotneutralize,bind
toinfected
cells,norserve
asim
munotoxins
[Pincus
etal.(1993)]•
C8:
Epitope
boundariesm
appedby
peptidescanning
[Abacioglu
etal.(1994)]
70388-158/02
gp41(732-752IIIB
)gp41(222-237)
GIE
EE
GG
ER
DR
DR
SIR
rgp41IIIB
murine(IgG
2b )
Donor:
Gearoge
Lewis
References:[N
iedrigetal.(1992a)]
NO
TE
S:
•88-158/02:
Mild
inhibitionofin
vitroactivity
athigh
MA
bconcentrations
–profound
enhancingactivity
atlow
concentrations–
significantreactivityto
virion–
domain
non-imm
unogenicin
humans
[Niedrig
etal.(1992a)]
70488-158/022
gp41(732-752IIIB
)gp41(222-237)
GIE
EE
GG
ER
DR
DR
SIR
rgp41IIIB
murine(IgG
2b )
Donor:
Gearoge
Lewis
References:[N
iedrigetal.(1992a)]
NO
TE
S:
•88-158/022:
Mild
inhibitionofin
vitroactivity
athigh
MA
bconcentrations
–profound
enhancingactivity
atlow
concentrations–
significantreactivityto
virion–
domain
non-imm
unogenicin
humans
[Niedrig
etal.(1992a)]
70588-158/079
gp41(732-752IIIB
)gp41(222-237)
GIE
EE
GG
ER
DR
DR
SIR
rgp41IIIB
murine(IgG
1 )D
onor:G
earogeLew
isR
eferences:[Niedrig
etal.(1992a)]N
OT
ES
:•
88-158/079:M
ildinhibition
ofH
IVin
vitroat
highM
Ab
concentrations–
profoundenhancing
activityat
lowconcentrations
–w
eakbinding
tovirion
–dom
ainnon-im
munogenic
inhum
ans[N
iedrigetal.(1992a)]
HIV
MonoclonalA
ntibodies
III-A-232
DE
C98
MA
bID
LocationW
EA
US
equenceN
eutralizingIm
munogen
Species(Isotype)
706B
8gp41(733-741
BH
10)gp41(223-231)
IEE
EG
GE
RD
Nm
is-foldedLA
Irgp160
murine(IgG
1 )
Donor:
Gearoge
Lewis
References:[P
incusetal.(1993),A
baciogluetal.(1994)]
NO
TE
S:
•B
8:A
bresponse
inIIIB
labw
orkersw
ascom
paredto
gp160LA
Ivaccine
recipients–
B8
was
usedas
acontrol–
thedom
inantresponseam
ongvaccinees
was
tothis
mid-gp41
region,butnotamong
theinfected
labw
orkers–
Abs
bindingthis
regiondo
notneutralize,bindto
infectedcells,nor
serveas
imm
unotoxins[P
incusetal.(1993)]
•B
8:E
pitopeboundaries
mapped
bypeptide
scanning[A
baciogluetal.(1994)]
707LA
9(121-
134)gp41(735-752
IIIB)
gp41(218-235)D
RP
EG
IEE
EG
GE
RD
RD
RS
N?
murine(IgM
)
Donor:
Gearoge
Lewis
References:[E
vansetal.(1989)]
708E
D6
gp41(735-752IIIB
)gp41(218-235)
DR
PE
GIE
EE
GG
ER
DR
DR
SN
?m
urine(IgM)
Donor:
Gearoge
Lewis
References:[E
vansetal.(1989)]
7091575
gp41(735-752IIIB
)gp41(218-235)
DR
PE
GIE
EE
GG
ER
DR
DR
SN
Poliovirus/gp41
peptidechim
eram
urine
Donor:
Gearoge
Lewis
References:[E
vansetal.(1989),Vella
etal.(1993),Burattietal.(1997)]
NO
TE
S:
•1575:
Neutralizing
activity,lessbroad
than1577
[Evans
etal.(1989)]•
1575:C
oreepitope:
IEE
E–
neutralizedIIIB
,butnotRF
orM
N[Vella
etal.(1993)]•
1575:S
tudyshow
sthatM
Ab
1575can
recognizethe
IEE
Esequence
inboth
gp41,andin
theH
PG
30region
ofthep17
protein–
motifis
conservedin
bothregions
indifferentH
IV-1
clades[B
urattietal.(1997)]
7101576
gp41(735-752IIIB
)gp41(218-235)
DR
PE
GIE
EE
GG
ER
DR
DR
SN
Poliovirus/gp41
peptidechim
eram
urine
Donor:
Gearoge
Lewis
References:[Vella
etal.(1993)]N
OT
ES
:•
1576:N
otneutralizing[Vella
etal.(1993)]
HIV
MonoclonalA
ntibodies
III-A-233
DE
C98
MA
bID
LocationW
EA
US
equenceN
eutralizingIm
munogen
Species(Isotype)
7111577
gp41(735-752IIIB
)gp41(218-235)
DR
PE
GIE
EE
GG
ER
DR
DR
SN
Poliovirus/gp41
peptidechim
eram
urine
Donor:
Morag
Ferguson
(NIB
SC
)R
eferences:[Evans
etal.(1989),D’S
ouzaetal.(1991),Vella
etal.(1993)]N
OT
ES
:•
1577:R
aisedagainstIIIB
peptidechim
era–
neutralizedA
fricanand
Am
ericanH
IV-1
labstrains
[Evans
etal.(1989)]•
1577:N
on-neutralizingin
thism
ulti-labstudy
[D’S
ouzaetal.(1991)]
•1577:
Core
epitope:E
RD
RD
–could
neutralizeH
IVIIIB
andH
IVR
F[Vella
etal.(1993)]•
1577:U
KM
edicalResearch
CouncilA
IDS
reagent:A
RP
317•
1577:N
IHA
IDS
Research
andR
eferenceR
eagentProgram
:1172
7121578
gp41(735-752IIIB
)gp41(218-235)
DR
PE
GIE
EE
GG
ER
DR
DR
SN
Poliovirus/gp41
peptidechim
eram
urine
Donor:
Morag
Ferguson
(NIB
SC
)R
eferences:[Evans
etal.(1989),Vellaetal.(1993)]
NO
TE
S:
•1578:
No
neutralizingactivity
–epitope
may
beform
edby
regionsfrom
bothpoliovirus
andH
IV[E
vansetal.(1989)]
•1578:
Core
epitope:IE
EE
–in
thisstudy,neutralized
IIIB,butnotR
For
MN
[Vellaetal.(1993)]
7131899
gp41(735-752IIIB
)gp41(218-235)
DR
PE
GIE
EE
GG
ER
DR
DR
SN
Poliovirus/gp41
peptidechim
eram
urine
Donor:
Morag
Ferguson
(NIB
SC
)R
eferences:[Vellaetal.(1993)]
NO
TE
S:
•1899:
Could
neutralizeH
IVIIIB
andH
IVR
F[Vella
etal.(1993)]
7141579
gp41(735-752IIIB
)gp41(218-235)
DR
PE
GIE
EE
GG
ER
DR
DR
SN
Poliovirus/gp41
peptidechim
eram
urine
Donor:
Morag
Ferguson
(NIB
SC
)R
eferences:[Vellaetal.(1993)]
NO
TE
S:
•1579:
Core
epitope:IE
EE
–neutralized
IIIB,butnotR
For
MN
[Vellaetal.(1993)]
HIV
MonoclonalA
ntibodies
III-A-234
DE
C98
MA
bID
LocationW
EA
US
equenceN
eutralizingIm
munogen
Species(Isotype)
7151583
gp41(735-752IIIB
)gp41(218-235)
DR
PE
GIE
EE
GG
ER
DR
DR
SN
Poliovirus/gp41
peptidechim
eram
urine
Donor:
Morag
Ferguson
(NIB
SC
)R
eferences:[Evans
etal.(1989),Vellaetal.(1993),S
attentauetal.(1995)]
NO
TE
S:
•1583:
Neutralizing
activity,lessbroad
than1577
[Evans
etal.(1989)]•
1583:C
oreepitope:
ER
DR
D–
Could
neutralizeH
IVIIIB
butnotHIV
RF
[Vellaetal.(1993)]
•1583:
Cytoplasm
icdom
ain,epitopenotexposed
atthesurface
ofHIV
-1infected
cells[S
attentauetal.(1995)]
7161907
gp41(735-752IIIB
)gp41(218-235)
DR
PE
GIE
EE
GG
ER
DR
DR
SN
Poliovirus/gp41
peptidechim
eram
urine
Donor:
Morag
Ferguson
(NIB
SC
)R
eferences:[Vellaetal.(1993)]
NO
TE
S:
•1907:
Could
notneutralizeH
IVIIIB
,RF
orM
N[Vella
etal.(1993)]
7171908
gp41(735-752IIIB
)gp41(218-235)
DR
PE
GIE
EE
GG
ER
DR
DR
SN
Poliovirus/gp41
peptidechim
eram
urine
Donor:
Morag
Ferguson
(NIB
SC
)R
eferences:[Evans
etal.(1989),Vellaetal.(1993),S
attentauetal.(1995)]
NO
TE
S:
•1908:
Neutralized
IIIB,butnotR
For
MN
[Vellaetal.(1993)]
•1908:
Cytoplasm
icdom
ain,epitopenotexposed
atthesurface
ofHIV
-1infected
cells[S
attentauetal.(1995)]
7181909
gp41(735-752IIIB
)gp41(218-235)
DR
PE
GIE
EE
GG
ER
DR
DR
SN
Poliovirus/gp41
peptidechim
eram
urine
Donor:
Morag
Ferguson
(NIB
SC
)R
eferences:[Vellaetal.(1993)]
NO
TE
S:
•1909:
Neutralized
HIV
IIIBbutnotH
IVR
F[Vella
etal.(1993)]
71941-1
gp41(735-752IIIB
)gp41(218-235)
DR
PE
GIE
EE
GG
ER
DR
DR
SN
Peptide
735-752IIIB
murine(IgM
κ )
Donor:
Morag
Ferguson
(NIB
SC
)R
eferences:[Dalgleish
etal.(1988)]N
OT
ES
:•
41-1:T
hisantibody
gp41(735-752IIIB
)[D
algleishetal.(1988)]seem
sto
havebeen
named
thesam
eas
adifferent
MA
bto
gp41(584-609)[M
anietal.(1994)]•
41-1:N
eutralizesH
IV-1
butnotHIV
-2strains
[Dalgleish
etal.(1988)]
HIV
MonoclonalA
ntibodies
III-A-235
DE
C98
MA
bID
LocationW
EA
US
equenceN
eutralizingIm
munogen
Species(Isotype)
72041-2
gp41(735-752IIIB
)gp41(218-235)
DR
PE
GIE
EE
GG
ER
DR
DR
SN
Peptide
735-752IIIB
murine(IgM
κ )
Donor:
Morag
Ferguson
(NIB
SC
)R
eferences:[Dalgleish
etal.(1988)]N
OT
ES
:•
41-2:N
eutralizesH
IV-1
butnotHIV
-2strains
[Dalgleish
etal.(1988)]
72141-3
gp41(735-752IIIB
)gp41(218-235)
DR
PE
GIE
EE
GG
ER
DR
DR
SN
Peptide
735-752IIIB
murine(IgM
κ )
Donor:
Morag
Ferguson
(NIB
SC
)R
eferences:[Dalgleish
etal.(1988)]N
OT
ES
:•
41-3:N
eutralizesH
IV-1
butnotHIV
-2strains
[Dalgleish
etal.(1988)]
7224E
10gp41(824-830
BH
10)gp41(313-319)
AE
GT
DR
VN
HIV
-1infection
human(IgG
3κ )
Donor:
Morag
Ferguson
(NIB
SC
)R
eferences:[Buchacher
etal.(1992),Buchacher
etal.(1994),D’S
ouzaetal.(1994)]
NO
TE
S:
•4E
10:M
Abs
generatedby
electrofusionofP
BL
fromH
IV-1+
volunteersw
ithC
B-F
7cells
–also
bindsto
MH
Cclass
IIproteins–
anti-classIIA
bsare
onlyfound
inH
IV-1
positivepeople
[Buchacher
etal.(1994)]•
4E10:
Includedin
am
ulti-labstudy
forantibody
characterization,binding
andneutralization
assaycom
parison[D
’Souza
etal.(1994)]
723D
Zgp41(827-860
BR
U)
gp41(312-345)VA
EG
TD
RV
IEV
VQ
GA
CR
-A
IRH
IPR
RIR
QG
LER
IL?L
recvaccinia
gp160IIIB
human(IgG
1λ )
Donor:
?R
eferences:[Boyer
etal.(1991)]N
OT
ES
:•
DZ
:Weakly
neutralizingIIIB
–binds
topeptides
827-843and
846-860ofB
RU
–reacted
specificallyw
ithIIIB
andR
F[B
oyeretal.(1991)]
724C
hessie8
gp41(cytoplasmic
domain)
gp41VA
EG
TD
RV
IEV
VQ
GA
CR
-A
IRH
IPR
RIR
QG
LER
IL?m
urine(IgG)
Donor:
G.Lew
isR
eferences:[Lewis
etal.(1991),Poum
bouriosetal.(1995),R
ovinskietal.(1995)]N
OT
ES
:•
Chessie
8:U
sedto
precipitategp160
inim
munoblots
ina
studyexam
iningthe
feasibilityofusing
unprocessedgp160
glycoproteinas
anim
munogen
[Rovinskietal.(1995)]
HIV
MonoclonalA
ntibodies
III-A-236
DE
C98
MA
bID
LocationW
EA
US
equenceN
eutralizingIm
munogen
Species(Isotype)
725K
14gp41(dis)
gp41(dis)D
ISC
ON
TIN
UO
US
Nhum
an(IgG1 )
Donor:
?R
eferences:[Teeuwsen
etal.(1990),
Schutten
etal.(1995a),
Schutten
etal.(1995b),
Schutten
etal.(1996),
Schutten
etal.(1997)]N
OT
ES
:•
K14:
Did
notbindto
peptidesspanning
gp41,butitdoesnotreactw
ithenv
deletionm
utant643-692–
doesnotreact
with
HIV
-2–
competition
experiments
showed
thisw
asan
imm
unodominant
conservedepitope
inH
IV-1
positivesera
fromE
uropeand
Africa
[Teeuwsen
etal.(1990)]•
K14:
Reduced
affinityfor
bothS
IandN
SIviruses
relativeto
MA
bM
N215,failed
toneutralize
SIstrain
[Schutten
etal.(1995b)]•
K14:
Ina
studyofN
SIand
SIvirus
neutralization,K14
didnotinfluence
viralentry[S
chuttenetal.(1997)]
726T
30gp41(dis)
gp41(dis)D
ISC
ON
TIN
UO
US
Ntetram
ericE
nvm
urineD
onor:?
References:[E
arletal.(1994),Earletal.(1997)]
NO
TE
S:
•T
30:binds
tothe
region580
to640,butdoes
notbindto
peptidesspanning
thisregion
–binding
dependson
N-linked
glycosylationofA
sn616
–no
otherantibody
testedinhibited
binding,butbinding
couldbe
inhibitedby
serafrom
HIV
+individuals
[Earletal.(1997)]
727126-50
gp41(disH
XB
2)gp41(dis)
DIS
CO
NT
INU
OU
SN
HIV
-1infection
human(IgG
2κ )
Donor:
?R
eferences:[Robinson
Jr.etal.(1990a),Tyler
etal.(1990),Robinson
Jr.etal.(1991),X
uetal.(1991)]
NO
TE
S:
•126-50:
No
enhancingactivity
forH
IV-1
IIIB[R
obinsonJr.
etal.(1990a)]•
126-50:S
ervesas
targetforantibody-dependentcellular
cytotoxicityA
DC
C[Tyler
etal.(1990)]•
126-50:N
oenhancing
orneutralizing
activity[R
obinsonJr.
etal.(1991)]•
126-50:S
pecificfor
aconform
ationalepitope[X
uetal.(1991)]
HIV
MonoclonalA
ntibodies
III-A-237
DE
C98
MA
bID
LocationW
EA
US
equenceN
eutralizingIm
munogen
Species(Isotype)
728T
4gp41(dis
IIIB)
gp41(dis)D
ISC
ON
TIN
UO
US
Lvaccinia
expressedoligom
ericgp140
IIIB
murine(IgG
)
Donor:
?R
eferences:[Earletal.(1994),B
roderetal.(1994),Richardson
Jretal.(1996),Weissenhorn
etal.(1996),Earletal.(1997),
Otteken
etal.(1996)]N
OT
ES
:•
T4:
oneof
fiveM
Abs
(T4,
T6,
T9,
T10
andT
35)in
acom
petitiongroup
thatbind
toa
conformation-dependent
epitopein
gp41and
isoligom
erspecific
–neutralizes
IIIBand
SF
2[B
roderetal.(1994)]
•T
4:D
oesnotbind
tosoluble
monom
ericgp41(21-166)
thatlacksthe
fusionpeptide
andm
embrane
anchor,onlyto
theoligom
ergp140,as
doesT
6[W
eissenhornetal.(1996)]
•T
4:T
hisantibody,
alongw
ith7
others(M
10,D
41,D
54,T
6,T
9,T
10and
T35),
canblock
thelinear
murine
MA
bD
61,andthe
human
MA
b246-D
,which
bothbind
tothe
imm
unodominantregion
nearthe
two
Cys
ingp41
–m
ostofthese
antibodiesare
oligomerdependent–
alloftheM
Abs
arereactive
with
tendifferentH
IV-1
strains–
mem
bersofthis
competition
groupare
blockedby
serafrom
HIV
-1+individuals
[Earletal.(1997)]
•M
Abs
T4
andT
6bind
onlyto
oligomer,and
pulsechase
experiments
indicatethatthe
epitopeis
veryslow
toform
,requiring
oneto
two
hours[O
ttekenetal.(1996)]
729D
12gp41(dis
IIIB)
gp41(dis)D
ISC
ON
TIN
UO
US
Lvaccinia
expressedoligom
ericgp140
IIIB
murine(IgG
)
Donor:
?R
eferences:[Broder
etal.(1994),Richardson
Jretal.(1996),E
arletal.(1997),Otteken
etal.(1996)]N
OT
ES
:•
D12:
One
of18
MA
bs(e.
g.D
4and
D40)
thatbind
toa
conformation-dependent
epitopein
gp41that
bindpreferentially,butnotexclusively,to
oligomers
–neutralizes
IIIBand
SF
2[B
roderetal.(1994)]
•D
12:T
hisantibody
was
blockedm
orestrongly
byhum
ansera
thanother
anti-gp41M
Abs
(D20,D
43,D61,and
T4)
ina
oligomeric
ELIS
Aassay
[Richardson
Jretal.(1996)]
•D
12:M
Abs
D10
andD
12are
veryeasily
blockedby
human
serafrom
HIV
+individuals
[Earletal.(1997)]
•D
12:M
Abs
D4,
D10,
D11,
D12,
andD
41allbind
onlyto
complete
oligomer
–pulse
labelexperiments
ofM
Ab
bindingto
noncleavablegp160
revealedthatthese
MA
bsbound
with
adelay,epitopes
forming
with
ahalflife
of30m
in[O
ttekenetal.(1996)]
HIV
MonoclonalA
ntibodies
III-A-238
DE
C98
MA
bID
LocationW
EA
US
equenceN
eutralizingIm
munogen
Species(Isotype)
730D
1gp41(dis
IIIB)
gp41(dis)D
ISC
ON
TIN
UO
US
vacciniaexpressed
oligomeric
gp140IIIB
murine(IgG
)
Donor:
?R
eferences:[Otteken
etal.(1996)]N
OT
ES
:•
D1:
MA
bsD
1,D
16,had
T37
bindto
oligomeric
gp160equally
well–
pulselabelexperim
entsof
MA
bbinding
tononcleavable
gp160revealed
thatthese
MA
bsbound
with
adelay,
epitopesform
ingw
itha
halflife
of30
min
[Otteken
etal.(1996)]
731D
16gp41(dis
IIIB)
gp41(dis)D
ISC
ON
TIN
UO
US
Ldim
ericE
nvm
urine(IgG)
Donor:
?R
eferences:[Earletal.(1994),W
eissenhornetal.(1996),E
arletal.(1997)]N
OT
ES
:•
D16:
Precipitates
botholigom
ericgp140
andsoluble
monom
ericgp41(21-166)that
lacksthe
fusionpeptide
andm
embrane
anchor,alongw
ithM
Abs
D16,D
38,D40,D
41,andD
54[W
eissenhornetal.(1996)]
•D
16:O
neofeleven
MA
bs(D
16,D17,D
31,D36,D
37,D40,D
44,D55,D
59,T37,and
T45)
thatareconform
ationdependentand
thatcanblock
thebinding
oftheM
Ab
D50
thatbindsto
thelinear
peptidegp41(642-665)
–reactive
with
9/10H
IV-1
strainsallexceptH
IV-1
AD
A,w
hichhas
thechange
E659D
andE
662Athatm
ayresultin
theloss
ofbinding(E
LLEto
DLLA
)[E
arletal.(1997)]
732126-6
gp41(disH
XB
2)gp41(dis)
DIS
CO
NT
INU
OU
SN
HIV
-1infection
human(IgG
2κ )
Donor:
Susan
Zolla-P
azner,NY
UM
edC
enter,NY,N
YR
eferences:[Robinson
Jr.et
al.(1990a),R
obinsonJr.
etal.(1991),
Xu
etal.(1991),
Eddleston
etal.(1993),
Chen
etal.(1995),Binley
etal.(1996),Earletal.(1997)]
NO
TE
S:
•126-6:
No
enhancingactivity
forH
IV-1
IIIB[R
obinsonJr.
etal.(1990a)]•
126-6:N
oenhancing
orneutralizing
activity[R
obinsonJr.
etal.(1991)]•
126-6:S
pecificfor
aconform
ationalepitope[X
uetal.(1991)]
•126-6:
Called
SZ
-126.6[E
ddlestonetal.(1993)]
•126-6:
One
ofseveral
anti-gp41M
Abs
thatbind
toa
gp41-maltose
bindingfusion
proteindesigned
tostudy
theleucine
zipperdom
ainofgp41,show
ingthatthe
constructhasretained
aspectsofnorm
algp41conform
ation[C
henetal.(1995)]
•126-6:
Discontinuous
epitoperecognizing
residuesbetw
een649-668
–designated
clusterII
–F
absD
5,D
11,G
1,T
3,M12,M
15,S6,S
8,S9,S
10block
binding[B
inleyetal.(1996)]
•126-6:
NIH
AID
SR
esearchand
Reference
ReagentP
rogram:
1243
HIV
MonoclonalA
ntibodies
III-A-239
DE
C98
MA
bID
LocationW
EA
US
equenceN
eutralizingIm
munogen
Species(Isotype)
733D
43gp41(dis
HX
B2)
gp41(dis)D
ISC
ON
TIN
UO
US
dimeric
Env
murine(IgG
)D
onor:S
usanZ
olla-Pazner,N
YU
Med
Center,N
Y,NY
References:[E
arletal.(1994),Richardson
Jretal.(1996),E
arletal.(1997)]N
OT
ES
:•
D43:
This
isa
lineargp41
epitope,m
appingin
theregion
635-678–
human
serablocked
bindingin
oligomeric
ELIS
Aassay
toa
similar
extentforgp41
MA
bsD
20,D43,D
61,andT
4[R
ichardsonJr
etal.(1996)]•
D43:
Partially
conformation
dependent–doesn’tbind
toshortpeptides,butdoes
bindto
theregion
spanning641-683
–binding
canbe
blockedby
MA
bsT
3,D
38and
D45
–M
Abs
inthis
competition
groupreacted
with
9/10H
IV-1
strains,notbindingto
JRF
L[E
arletal.(1997)]
734T
3gp41(dis
HX
B2)
gp41(dis)D
ISC
ON
TIN
UO
US
tetrameric
Env
murine(IgG
)D
onor:S
usanZ
olla-Pazner,N
YU
Med
Center,N
Y,NY
References:[E
arletal.(1994),Earletal.(1997)]
NO
TE
S:
•T
3:P
artiallyconform
ationdependent–
doesn’tbindto
shortpeptides,butdoesbind
tothe
regionspanning
641-683–
bindingcan
beblocked
byM
Abs
D43,
D38
andD
45–
MA
bsin
thiscom
petitiongroup
reactedw
ith9/10
HIV
-1strains,notbinding
toJR
FL
[Earletal.(1997)]
735M
d-1gp41(dis)
gp41(dis)D
ISC
ON
TIN
UO
US
N?
human(IgG
1λ )
Donor:
R.A
.Myers
State
ofMaryland
Dept.
ofHealth
References:[M
yersetal.(1993),C
henetal.(1995),B
inleyetal.(1996)]
NO
TE
S:
•M
d-1:A
lsocalled
MD
-1•
Md-1:
Called
MD
-1–
discontinuousepitope
thatbindsin
theN
-terminalregion
–reacts
exclusivelyw
itholigom
er[M
yersetal.(1993)]
•M
d-1:C
alledM
D-1
–one
ofseveralanti-gp41M
Abs
thatbindto
agp41-m
altosebinding
fusionprotein
designedto
studythe
leucinezipperdom
ainofgp41,show
ingthatthe
constructhasretained
aspectsofnorm
algp41conform
ation[C
henetal.(1995)]
•M
d-1:D
iscontinuousepitope
recognizingresidues
between
563-672,does
notrecognize
clusterI
disulfidebridge
region–
reactsalm
ostexclusivelyw
ithtrim
ersand
tetramers
onW
B–
designatedcluster
II–F
absD
5,D11,G
1,T3,
M12,M
15,S6,S
8,S9,S
10block
binding[B
inleyetal.(1996)]
•M
d-1:N
IHA
IDS
Research
andR
eferenceR
eagentProgram
:1223
HIV
MonoclonalA
ntibodies
III-A-240
DE
C98
MA
bID
LocationW
EA
US
equenceN
eutralizingIm
munogen
Species(Isotype)
736F
abD
5gp41(dis
LAI)
gp41(dis)D
ISC
ON
TIN
UO
US
NH
IV-1
infectionhum
an(IgG1κ )
Donor:
R.A
.Myers
State
ofMaryland
Dept.
ofHealth
References:[B
inleyetal.(1996)]
NO
TE
S:
•F
abD
5:B
indsto
Cluster
IIregion–
competes
with
MA
bs126-6,M
d-1and
D50
–conform
ationsensitive
–variable
regionssequenced
[Binley
etal.(1996)]
737F
abD
11gp41(dis
LAI)
gp41(dis)D
ISC
ON
TIN
UO
US
NH
IV-1
infectionhum
an(IgG1κ )
Donor:
R.A
.Myers
State
ofMaryland
Dept.
ofHealth
References:[B
inleyetal.(1996)]
NO
TE
S:
•F
abD
11:B
indsto
ClusterIIregion
–com
petesw
ithM
Abs
126-6,Md-1
andD
50–
conformation
sensitive–
variableregions
sequenced[B
inleyetal.(1996)]
738F
abG
1gp41(dis
LAI)
gp41(dis)D
ISC
ON
TIN
UO
US
NH
IV-1
infectionhum
an(IgG1κ )
Donor:
R.A
.Myers
State
ofMaryland
Dept.
ofHealth
References:[B
inleyetal.(1996)]
NO
TE
S:
•F
abG
1:B
indsto
Cluster
IIregion–
competes
with
MA
bs126-6,M
d-1and
D50
–conform
ationsensitive
–variable
regionssequenced
[Binley
etal.(1996)]
739F
abT
3gp41(dis
LAI)
gp41(dis)D
ISC
ON
TIN
UO
US
NH
IV-1
infectionhum
an(IgG1κ )
Donor:
R.A
.Myers
State
ofMaryland
Dept.
ofHealth
References:[B
inleyetal.(1996)]
NO
TE
S:
•F
abT
3:B
indsto
Cluster
IIregion–
competes
with
MA
bs126-6,M
d-1and
D50
–conform
ationsensitive
–variable
regionssequenced
[Binley
etal.(1996)]
740F
abM
10gp41(dis
LAI)
gp41(dis)D
ISC
ON
TIN
UO
US
NH
IV-1
infectionhum
an(IgG1κ )
Donor:
R.A
.Myers
State
ofMaryland
Dept.
ofHealth
References:[B
inleyetal.(1996),P
arrenetal.(1997b)]
NO
TE
S:
•F
abM
10:B
indsto
ClusterIIregion
–com
petesw
ithM
Abs
126-6,Md-1
andD
50–
conformation
sensitive–
variableregions
sequenced[B
inleyetal.(1996)]
•F
abM
10:D
oesnot
bindto
MN
nativeoligom
er,but
doesbind
toboth
LAI
andM
Nrgp120
andrgp140
[Parren
etal.(1997b)]
HIV
MonoclonalA
ntibodies
III-A-241
DE
C98
MA
bID
LocationW
EA
US
equenceN
eutralizingIm
munogen
Species(Isotype)
741F
abM
12gp41(dis
LAI)
gp41(dis)D
ISC
ON
TIN
UO
US
NH
IV-1
infectionhum
an(IgG1κ )
Donor:
R.A
.Myers
State
ofMaryland
Dept.
ofHealth
References:[B
inleyetal.(1996)]
NO
TE
S:
•F
abM
12:B
indsto
ClusterIIregion
–com
petesw
ithM
Abs
126-6,Md-1
andD
50–
conformation
sensitive–
variableregions
sequenced[B
inleyetal.(1996)]
742F
abM
15gp41(dis
LAI)
gp41(dis)D
ISC
ON
TIN
UO
US
NH
IV-1
infectionhum
an(IgG1κ )
Donor:
R.A
.Myers
State
ofMaryland
Dept.
ofHealth
References:[B
inleyetal.(1996)]
NO
TE
S:
•F
abM
15:B
indsto
ClusterIIregion
–com
petesw
ithM
Abs
126-6,Md-1
andD
50–
conformation
sensitive–
variableregions
sequenced[B
inleyetal.(1996)]
743F
abS
6gp41(dis
LAI)
gp41(dis)D
ISC
ON
TIN
UO
US
NH
IV-1
infectionhum
an(IgG1κ )
Donor:
R.A
.Myers
State
ofMaryland
Dept.
ofHealth
References:[B
inleyetal.(1996)]
NO
TE
S:
•F
abS
6:B
indsto
Cluster
IIregion–
competes
with
MA
bs126-6,M
d-1and
D50
–conform
ationsensitive
–variable
regionssequenced
[Binley
etal.(1996)]
744F
abS
8gp41(dis
LAI)
gp41(dis)D
ISC
ON
TIN
UO
US
NH
IV-1
infectionhum
an(IgG1κ )
Donor:
R.A
.Myers
State
ofMaryland
Dept.
ofHealth
References:[B
inleyetal.(1996)]
NO
TE
S:
•F
abS
8:B
indsto
Cluster
IIregion–
competes
with
MA
bs126-6,M
d-1and
D50
–conform
ationsensitive
–variable
regionssequenced
[Binley
etal.(1996)]
745F
abS
9gp41(dis
LAI)
gp41(dis)D
ISC
ON
TIN
UO
US
NH
IV-1
infectionhum
an(IgG1κ )
Donor:
R.A
.Myers
State
ofMaryland
Dept.
ofHealth
References:[B
inleyetal.(1996)]
NO
TE
S:
•F
abS
9:B
indsto
Cluster
IIregion–
competes
with
MA
bs126-6,M
d-1and
D50
–conform
ationsensitive
–variable
regionssequenced
[Binley
etal.(1996)]
HIV
MonoclonalA
ntibodies
III-A-242
DE
C98
MA
bID
LocationW
EA
US
equenceN
eutralizingIm
munogen
Species(Isotype)
746F
abS
10gp41(dis
LAI)
gp41(dis)D
ISC
ON
TIN
UO
US
NH
IV-1
infectionhum
an(IgG1κ )
Donor:
R.A
.Myers
State
ofMaryland
Dept.
ofHealth
References:[B
inleyetal.(1996)]
NO
TE
S:
•F
abS
10:B
indsto
ClusterIIregion
–com
petesw
ithM
Abs
126-6,Md-1
andD
50–
conformation
sensitive–
variableregions
sequenced[B
inleyetal.(1996)]
747F
abL2
gp41(disLA
I)gp41(dis)
DIS
CO
NT
INU
OU
SN
HIV
-1infection
human(IgG
1κ )
Donor:
P.Perrin
andD
.Burton
(Scripps
Research
Institute,LaJolla,C
aliforniaR
eferences:[Binley
etal.(1996),Earletal.(1997)]
NO
TE
S:
•F
abL2:
Binds
toC
lusterIII
region–
competes
with
MA
bM
d-1,but
notM
Abs
126-6and
D50
–conform
ationsensitive
–variable
regionssequenced
[Binley
etal.(1996)]
748F
abL11
gp41(disLA
I)gp41(dis)
DIS
CO
NT
INU
OU
SN
HIV
-1infection
human(IgG
1κ )
Donor:
P.Perrin
andD
.Burton
(Scripps
Research
Institute,LaJolla,C
aliforniaR
eferences:[Binley
etal.(1996)]N
OT
ES
:•
Fab
L11:B
indsto
Cluster
IIIregion
–com
petesw
ithM
Ab
Md-1,
butnot
MA
bs126-6
andD
50–
conformation
sensitive–
variableregions
sequenced[B
inleyetal.(1996)]
749F
abL1
gp41(disLA
I)gp41(dis)
DIS
CO
NT
INU
OU
SN
HIV
-1infection
human(IgG
1κ )
Donor:
P.Perrin
andD
.Burton
(Scripps
Research
Institute,LaJolla,C
aliforniaR
eferences:[Binley
etal.(1996)]N
OT
ES
:•
Fab
L1:B
indsto
Cluster
IIIregion
–com
petesw
ithM
Ab
Md-1,
butnot
MA
bs126-6
andD
50–
conformation
sensitive–
variableregions
sequenced[B
inleyetal.(1996)]
750F
abG
5gp41(dis
LAI)
gp41(dis)D
ISC
ON
TIN
UO
US
NH
IV-1
infectionhum
an(IgG1κ )
Donor:
P.Perrin
andD
.Burton
(Scripps
Research
Institute,LaJolla,C
aliforniaR
eferences:[Binley
etal.(1996)]N
OT
ES
:•
Fab
G5:
Binds
toC
lusterIII
region–
competes
with
MA
bM
d-1,but
notM
Abs
126-6and
D50
–conform
ationsensitive
–variable
regionssequenced
[Binley
etal.(1996)]
HIV
MonoclonalA
ntibodies
III-A-243
DE
C98
MA
bID
LocationW
EA
US
equenceN
eutralizingIm
munogen
Species(Isotype)
751F
abG
15gp41(dis
LAI)
gp41(dis)D
ISC
ON
TIN
UO
US
NH
IV-1
infectionhum
an(IgG1κ )
Donor:
P.Perrin
andD
.Burton
(Scripps
Research
Institute,LaJolla,C
aliforniaR
eferences:[Binley
etal.(1996)]N
OT
ES
:•
Fab
G15:
Binds
toC
lusterIII
region–
competes
with
MA
bM
d-1,but
notM
Abs
126-6and
D50
–conform
ationsensitive
–variable
regionssequenced
[Binley
etal.(1996)]
752F
abA
9gp41(dis
LAI)
gp41(dis)D
ISC
ON
TIN
UO
US
NH
IV-1
infectionhum
an(IgG1κ )
Donor:
P.Perrin
andD
.Burton
(Scripps
Research
Institute,LaJolla,C
aliforniaR
eferences:[Binley
etal.(1996)]N
OT
ES
:•
Fab
A9:
Binds
toC
lusterIII
region–
competes
with
MA
bM
d-1,but
notM
Abs
126-6and
D50
–conform
ationsensitive
–variable
regionssequenced
[Binley
etal.(1996)]
753F
abA
12gp41(dis
LAI)
gp41(dis)D
ISC
ON
TIN
UO
US
NH
IV-1
infectionhum
an(IgG1κ )
Donor:
P.Perrin
andD
.Burton
(Scripps
Research
Institute,LaJolla,C
aliforniaR
eferences:[Binley
etal.(1996)]N
OT
ES
:•
Fab
A12:
Uncharacterized
epitope–
variableregions
sequenced[B
inleyetal.(1996)]
754F
abL9
gp41(disLA
I)gp41(dis)
DIS
CO
NT
INU
OU
SN
HIV
-1infection
human(IgG
1κ )
Donor:
P.Perrin
andD
.Burton
(Scripps
Research
Institute,LaJolla,C
aliforniaR
eferences:[Binley
etal.(1996)]N
OT
ES
:•
Fab
L9:U
ncharacterizedepitope
–variable
regionssequenced
[Binley
etal.(1996)]
755F
abA
2gp41(dis
LAI)
gp41(dis)D
ISC
ON
TIN
UO
US
NH
IV-1
infectionhum
an(IgG1λ )
Donor:
P.Perrin
andD
.Burton
(Scripps
Research
Institute,LaJolla,C
aliforniaR
eferences:[Binley
etal.(1996)]N
OT
ES
:•
Fab
A2:
Uncharacterized
epitope–
variableregions
sequenced[B
inleyetal.(1996)]
756H
2gp41(dis)
gp41(dis)D
ISC
ON
TIN
UO
US
?hum
an(IgMκ )
Donor:
BioInvent,Lund,S
weden,com
mercial
References:[M
ulleretal.(1991)]
NO
TE
S:
•H
2:A
nti-idiotypicM
Abs
(10B3
and2A
ll)againstH
2w
eregenerated
byim
munization
ofBA
LB/c
mice
with
H2
–they
alsoreactw
ithseropositive
sera[M
ulleretal.(1991)]
HIV
MonoclonalA
ntibodies
III-A-244
DE
C98
MA
bID
LocationW
EA
US
equenceN
eutralizingIm
munogen
Species(Isotype)
757M
O43
gp41(dis)gp41(dis)
DIS
CO
NT
INU
OU
SN
invitro
rE
nvpenv9
human(IgM
)
Donor:
?R
eferences:[Ohlin
etal.(1989)]N
OT
ES
:•
MO
43:D
iscontinuousepitope
involvinghydrophobic
regions632-646,
677-681and
687-691,proxim
alto
andspanning
thetransm
embrane
region–
thisspecificity
isunusualin
HIV
-1positive
sera[O
hlinetal.(1989)]
758M
O30
gp41(dis)gp41(dis)
DIS
CO
NT
INU
OU
SN
invitro
rE
nvpenv9
human(IgM
)
Donor:
?R
eferences:[Ohlin
etal.(1989)]N
OT
ES
:•
MO
30:D
iscontinuousepitope
involvinghydrophobic
regions632-646,
677-681and
687-691,proxim
alto
andspanning
thetransm
embrane
region–
thisspecificity
isunusualin
HIV
-1positive
sera[O
hlinetal.(1989)]
759M
O28
gp41(dis)gp41(dis)
DIS
CO
NT
INU
OU
SN
invitro
rE
nvpenv9
human(IgM
)
Donor:
?R
eferences:[Ohlin
etal.(1989)]N
OT
ES
:•
MO
28:D
iscontinuousepitope
involvinghydrophobic
regions632-646,
677-681and
687-691,proxim
alto
andspanning
thetransm
embrane
region–
thisspecificity
isunusualin
HIV
-1positive
sera[O
hlinetal.(1989)]
7602A
2gp41(N
-term)
gp41(dis)?
NH
IV-1
infectionhum
an(IgG1κ )
Donor:
?R
eferences:[Weissenhorn
etal.(1996)]N
OT
ES
:•
Soluble
gp41(21-166)form
sa
rodlike
structurethatcan
bevisualized
with
electronm
icroscopy,and
2A2
bindsto
oneend
oftherod
[Weissenhorn
etal.(1996)]
HIV
MonoclonalA
ntibodies
III-A-245
DE
C98
MA
bID
LocationW
EA
US
equenceN
eutralizingIm
munogen
Species(Isotype)
761N
2-4gp41
gp41?
NH
IV-1
infectionhum
an(IgG1κ )
Donor:
Evan
Hersh
andYoh-IchiM
atsumoto
References:[R
obinsonJr.
etal.(1990a)]N
OT
ES
:•
N2-4:
No
enhancingactivity
forH
IV-1
IIIB[R
obinsonJr.
etal.(1990a)]•
N2-4:
NIH
AID
SR
esearchand
Reference
ReagentP
rogram:
528
762M
25gp41
gp41?
purifiedH
TLV
-IIIm
urine(IgGκ )D
onor:E
vanH
ershand
Yoh-IchiMatsum
otoR
eferences:[diMarzo
Veroneseetal.(1985),W
atkinsetal.(1996)]
NO
TE
S:
•M
25:heavy
andlight
chainscloned
andsequenced
–binding
requiresheavy
andlight
chainin
combination,
incontrastto
M77
[Watkins
etal.(1996)]
76310E
9gp41
gp41?
HIV
-1infection
murine(IgG
1 )D
onor:E
vanH
ershand
Yoh-IchiMatsum
otoR
eferences:[Papsidero
etal.(1988)]N
OT
ES
:•
10E9:
100/100H
IV+
human
seracould
inhibit10E9
binding[P
apsideroetal.(1988)]
76431A
1gp41
gp41?
Nin
vitroim
muniza-
tion,denatured
HIV
-1
human(IgM
κ/λ )
Donor:
?R
eferences:[Pollock
etal.(1989)]N
OT
ES
:•
31A1:
Reacts
with
bothp24
andgp41
[Pollock
etal.(1989)]
76539A
64gp41
gp41?
Nin
vitroim
muniza-
tion,denatured
HIV
-1
human(IgM
κ/λ )
Donor:
?R
eferences:[Pollock
etal.(1989)]N
OT
ES
:•
39A64:
Reacts
with
bothp24
andgp41
[Pollock
etal.(1989)]
HIV
MonoclonalA
ntibodies
III-A-246
DE
C98
MA
bID
LocationW
EA
US
equenceN
eutralizingIm
munogen
Species(Isotype)
76639B
86gp41
gp41?
Nin
vitroim
muniza-
tion,denatured
HIV
-1
human(IgM
κ/λ )
Donor:
?R
eferences:[Pollock
etal.(1989)]N
OT
ES
:•
39B86:
Reacts
with
bothp24
andgp41
[Pollock
etal.(1989)]
7679303
gp41gp41
Nm
urineD
onor:D
uP
ontR
eferences:[McD
ougaletal.(1996)]
7683H
6gp41
gp41m
urineD
onor:D
uP
ontR
eferences:[Pinter
etal.(1995)]N
OT
ES
:•
3H6:
There
isanother
MA
bw
iththis
IDthatrecognizes
Rev
[Orsinietal.(1995)]
•3H
6:G
eneratedin
responseto
virusgrow
nin
protein-freem
edium[P
interetal.(1995)]
76931710B
gp41gp41
human(IgG
1)D
onor:D
uP
ontR
eferences:[Alsm
adi&T
illey(1998)]N
OT
ES
:•
31710B:A
studyof6
anti-Env
MA
bsand
theirability
tobind
ordirectA
DC
Cagainsttargetcells
infectedw
ithIIIB
,M
N,S
F-2,and
RF
–bound
anddirected
lysisagainstallfour
strains[A
lsmadi&
Tilley(1998)]