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Influenza vaccines in infants and elderly, 25 March 20141 |
Infants and Elderly: is your vaccine approved for
these groups?
25 March 2014
Infants and Elderly: is your vaccine approved for
these groups?
25 March 2014
Influenza vaccines in infants and elderly, 25 March 20142 |
Available Influenza vaccines - USA, 2013–14 influenza seasonTIV Standard dose
(http://www.cdc.gov/flu/protect/vaccine/vaccines.htm)
Available Influenza vaccines - USA, 2013–14 influenza seasonTIV Standard dose
(http://www.cdc.gov/flu/protect/vaccine/vaccines.htm)
Trade name Manufacturer Presentation Mercury content (µg Hg/0.5 mL)
Age indications Route
Afluria bioCSL
0.5 mL single-dose prefilled syringe
0 ≥9 yrs
IM5.0 mL MDV 24.5 ≥9 yrs
Fluarix GSK 0.5 mL single-dose prefilled syringe
0 ≥3 yrs IM
Flucelvax Novartis 0.5 mL single-dose prefilled syringe
0 ≥18 yrs IM
FluLaval ID Biomedical Corporation of Quebec
5.0 mL MDV ≥25 ≥3 yrs IM
Fluvirin Novartis 0.5 mL single-dose prefilled syringe
≤1≥4 yrs
IM5.0 mL MDV 25.0
Fluzone Sanofi Pasteur
0.25 mL single-dose prefilled syringe
0 6-35 mo IM
0.5 mL single-dose prefilled syringe
0 ≥36 mo IM
0.5 mL single-dose prefilled vial
0 ≥36 mo IM
5.0 mL MDV 25.0 ≥6 mo IM
Fluzoneintradermal
Sanofi Pasteur 0.1 mL prefilled microinjection
system
0 18-64 yrs ID
Influenza vaccines in infants and elderly, 25 March 20143 |
Available Influenza vaccines - USA, 2013–14 influenza season(http://www.cdc.gov/flu/protect/vaccine/vaccines.htm)
Available Influenza vaccines - USA, 2013–14 influenza season(http://www.cdc.gov/flu/protect/vaccine/vaccines.htm)
Vaccine Trade name Manufacturer Presentation Mercury content
(µg Hg/0.5 mL)
Age indication
s
Route
Inactivated Influenza Vaccine,
Trivalent, High Dose
Fluzone High-Dose
Sanofi Pasteur0.5 mL single-dose
prefilled syringe
0 ≥65 yrs IM
Inactivated Influenza Vaccine,
Quadrivalent, Standard Dose
Fluarix Quadrivalent
GlaxoSmithKline0.5 mL single-dose
prefilled syringe0.0
≥3 yrs IM
FluLaval Quadrivalent
ID Biomedical Corporation of
Quebec
5.0 mL multi-dose vial
<25.0
≥3 yrs IM
Fluzone Quadrivalent
Sanofi Pasteur
0.25 mL single-dose prefilled syringe
0.0≥3 yrs IM
0.5 mL single-dose prefilled syringe
0.0
≥4 yrs IM0.5 mL single-dose
vial0.0
Recombinant Influenza Vaccine,
Trivalent FluBlok Protein Sciences
0.5 mL single-dose vial
0.0 18-49 yrs IM
Live-attenuated Influenza Vaccine,
Quadrivalent
FluMist Quadrivalent
MedImmune0.2 mL prefilled
intranasal sprayer0.0 (per 0.2 mL) 2-49 yrs IN
Influenza vaccines in infants and elderly, 25 March 20144 |
Influenza Vaccines in Europe http://www.ecdc.europa.eu/en/healthtopics/seasonal_influenza/vaccines/Pages/influenza_vaccination.aspx
Influenza Vaccines in Europe http://www.ecdc.europa.eu/en/healthtopics/seasonal_influenza/vaccines/Pages/influenza_vaccination.aspx
Manufacturer Name of product Vaccine type Administration route
Age recommended
Abbot healthcare Influvac Inactivated im >6 mthImuvac
AstraZeneca Fluenz Live attenuated intranasal 24 mth to 17 yrs(US trade name Flumist)
Baxter Preflucel Inactivated im >18 yrs
Crucell Viroflu Inactivated/virosomal im >6 mth, increased fever reported in children 6 mth to 5 yrs
Inflexal Inactivated/virosomal im
GlaxoSmithKline Fluarix Inactivated im >6 mthNovartis Agrippal Inactivated im >6 mth
Fluvirin Inactivated im >4 yrs
Optaflu Inactivated im >18 yrs
Fluad
(MF59)
Inactivated im >65 yrs
Omninvest Fluval AB Inactivated im >6 mthPfizer/CSL Australia Afluria Inactivated im
>5 yrsEnzira Inactivated im
Sanofi Pasteur Vaxigrip** Inactivated im >6 mth
Intanza 9µg Inactivated Intradermal >18-59 yrs
Intanza 15µg Inactivated Intradermal >60 yrs
Influenza vaccines in infants and elderly, 25 March 20145 |
Seasonal Influenza vaccines registered in Australia[Inactivated, IM, 45ug (3 x 15ug) total dose for adults]
Seasonal Influenza vaccines registered in Australia[Inactivated, IM, 45ug (3 x 15ug) total dose for adults]
Currently used � Agrippal (Novartis) (>6mo)
� Fluarix (GSK) (>6mo)
� Fluvax (BioCSL) (>5; 5-9 RA)
� Influvac (Abbott) (>6mo)– Influvac Jr (Abbott)
� Vaxigrip (Sanofi Pasteur) (>6mo)– Vaxigrip Jr (Sanofi Pasteur)
� Intanza (Sanofi Pasteur) (9ug SC) (18-59)
Currently Not supplied� FluAd (Novartis)
(>65y)
� Fluarix Quadrivalent
(GSK) (>3)
� XFLU (GSK)
Influenza vaccines in infants and elderly, 25 March 20146 |
WHO Age indication (y)
1 Flulaval GSK (IDBiomed) TIV 12-59
2 GC Flu Green Cross TIV 1-59
3 Fluvirin Novartis, UK TIV 1+
4 Vaxigrip Sanofi (France) TIV 1+
5 Fluzone Sanofi (US) TIV 1+
Canada
1 Influvac Abbott TIV subunit 18+
2 Fluviral GSK TIV split 1+
3 Agriflu Novartis TIV subunit 1+
4 Fluad Novartis TIV subunit + Adj. >65
5 Vaxigrip Sanofi TIV split 1+
6 Fluzone Sanofi TIV split 1+
7 Intanza Sanofi TIV-split ID 18+
8 FluMist Medimmune LAIV 2-59
Influenza vaccines in infants and elderly, 25 March 20147 |
China – TIV split or subunitChina – TIV split or subunit
Age indication
1 Seasonal influenza Beijing Tiantan Biological Products Co., Ltd >4
2 Seasonal influenza Sinovac Biotech Co., Ltd. 1+
3 Seasonal influenza Changchu Institute of Biological Products 1+
4 Seasonal influenza Changchun Changsheng Life Science Co. , Ltd. 1+
5 Seasonal influenza Shanghai Institute of Biological Products 1+
6 Seasonal influenza Hualan Biological Engineering Inc. 1+
7 Seasonal influenza Dalian Hissen Bio-pharm Co., Ltd. 1+
8 Seasonal influenza Dalian Aleph Biomedical Co., Ltd. >4
9 Seasonal influenza Jiangsu Simcere Vaxtec Bio-Pharmac. Co.,Ltd. 1+
10 Seasonal influenza Tasly Jenner Biotech Co., Ltd. Tianjin (sub unit) 1+
11 Seasonal influenza Lanzhou Institute of Biological Products 1+
12 Seasonal influenza Zhejiang Tianyuan Bio-Pharma Co.,Ltd 1+
13 Seasonal influenza Shenzhen Sanofi P. Biol. Products Co., Ltd. 1+
Influenza vaccines in infants and elderly, 25 March 20148 |
ThailandThailand
Age indication
1 Agrippal S Novartis Germ. TIV 1+
2 Fluzone Sanofi US TIV >3
3 Fluarix GSK, Germ. TIV 1+
4 Vaxigrip Sanofi Fr. TIV-split 1+
5 Fluad Novartis Germ.
TIV subunit +
Adj.1+
6 Fluarix NH GSK, Germ. TIV 1+
7 Influenza vaccine
Sanofi F-GPO-
MBP TIV1+
8 Inflexal V Crucell Switz. Viros adj 1+
9
Split Influenza
Vaccine SIBP, China TIV1+
10 Begrivac Novartis Germ. TIV-split 1+
11 Influvac Abbott NL TIV 1+
12 Intanza 9 ug Sanofi TIV-split ID >18
Influenza vaccines in infants and elderly, 25 March 20149 |
MexicoMexico
Age indication
1 Fluzone Sanofi US 1+ TIV
2 Vaxigrip Sanofi F 1+ TIV
3 Fluarix GSK B 1+ TIV
4 Agrippal S1 Novartis, Siena 1+ TIV-subunit
5 Influvac Abbott, NL 1+ TIV
6 Fluad Novartis, Siena >4 TIV subunit + Adj.
7 Fluvirene Novartis, UK >4 TIV
8 IDFlu Sanofi F >4 TIV-split ID
9 Ollinflu Birmex (SF) 1+ TIV
10 Fluvaxsin-SV Lab. Imp (Anflu-Sinovac)1+ split
Influenza vaccines in infants and elderly, 25 March 201410 |
Brazil Age indication
1 Sanofi >2
2 GSK >2
3 Butantan >2
4 Novartis ? ??
Kazakhstan
1 Agrippal S1 Novartis, I >1 TIV-subunit
2 Influvac Abbott, NL >1 TIV
3 Fluarix GSK, G >1 TIV-split
4 Vaxigrip Sanofi, F >1 TIV-split
5 Grippol Petrovax, R >1 TIV-subunit-pol
Romania
1 Fluarix GSK, B >3 TIV
2 Influvac Abbott. NL >1 TIV
3 Intanza /IDFlu Sanofi, F >18 TIV-split ID
4 Optaflu Novartis >18 TIV-cell based
5 Vaxigrip Sanofi, F >1 TIV
Influenza vaccines in infants and elderly, 25 March 201411 |
Iran
1 Agrippal Novartis >1
2 Fluad Medimmune >1
3 Fluarix GSK >1
4 Inflexal Crucell Switz. >1
5 Vaxigrip Sanofi >1
Indonesia
1 Vaxigrip Sanofi >1
2 Fluarix GSK >1
3 Agrippal Novartis >1
4 Flubio Bio Farma >18
Serbia
1 Fluad Novartis >65
2 Fluarix GSK >7
3 Fluimum ? >3
4 Intanza Sanofi >59
5 Vaxigrip Sanofi >1
Influenza vaccines in infants and elderly, 25 March 201412 |
Differing age indications between countries
Differing age indications between countries
* UK approval
Vaccine EU USA Canada Australia Mexico Serbia Thailand
Fluarix
(GSK)
> 6 months* > 3 years N/A > 6 months > 6 months > 7 years > 6 months
Influvac
(Abbott)
> 6 months* N/A > 18 years > 6 months > 4 years N/A > 6 months
Fluvax
/Afluria/
Enzira
(Bio-CSL)
> 5 Years > 5 Years** N/A > 5 Years** N/A N/A N/A
** 5-9 years use on careful consideration of risks vs benefits
Influenza vaccines in infants and elderly, 25 March 201413 |
Fluarix (GSK) in the UK> 6 months
Fluarix (GSK) in the UK> 6 months
Influenza vaccines in infants and elderly, 25 March 201414 |
Fluarix (GSK) in the US> 3 years
Fluarix (GSK) in the US> 3 years
Influenza vaccines in infants and elderly, 25 March 201415 |
Influvac (Abbott) in UK> 6 months
Influvac (Abbott) in UK> 6 months
Influenza vaccines in infants and elderly, 25 March 201416 |
Influvac (Abbott) in Canada> 18 years
Influvac (Abbott) in Canada> 18 years
Influenza vaccines in infants and elderly, 25 March 201417 |
Fluvax / Afluria (Bio CSL) > 5 years
Fluvax / Afluria (Bio CSL) > 5 years
Influenza vaccines in infants and elderly, 25 March 201418 |
In some studies, split vaccine can be poorly immunogenic in infants
In some studies, split vaccine can be poorly immunogenic in infants
Vesikari et al 2009
% HI>40% HI>40
primeprime boostboostAdjuvant noneAdjuvant none Adjuvant noneAdjuvant none
Influenza vaccines in infants and elderly, 25 March 201419 |
And in some studies efficacy can also be low…
And in some studies efficacy can also be low…
Vesikari 2011 NEJM
Age Relative efficacy (95% CI)TIV
6-72 Mo 43 (15-61)
36-72 45 (6-68)
6-36 40 (-6-66)
6-24 11 (-89-58)
Influenza vaccines in infants and elderly, 25 March 201420 |
Vaccine efficacy in the elderlyVaccine efficacy in the elderly
� "young elderly vs old elderly "
� TIV vs adjuvanted TIV in: 65-75, 75-85, >85yr
Van Buynder et al. 2013 Vaccine 31, 6122
� Not all elderly are the same…
Population VE% (univariate)
TIV TIV + adjuvant
All -12 35
Not in long-term care 42 73
Influenza vaccines in infants and elderly, 25 March 201421 |
Alternative vaccines for the elderlyAlternative vaccines for the elderly
� Adjuvant
� Intradermal delivery
� High dose antigen
– (60 ug vs 15)
0
10
2
4
6
8
ID IMGMTR
HAI GMT
H1N1 H3N2 B
High dose
60 ug
116 609 69
Normal
dose 15 ug
67 333 52
Influenza vaccines in infants and elderly, 25 March 201422 |
ConclusionsConclusions
� SAGE recommendations include infants and elderly as
priority groups.
– Age indications vary between countries
� Developing vaccines for use in these populations should
include data generation on safety and efficacy
– These populations are variable and clinical trial design and
product development should take this into account
� For these populations there are opportunities to make
targetted improved vaccines
– E.g. SC vaccines, high dose, adjuvanted vaccines, LAIVs,
Influenza vaccines in infants and elderly, 25 March 201423 |
Considerations for QIVsConsiderations for QIVs
Clinical
Is there interference between the Bs for Ab. response?
Potential extra ADRs because of extra 33 percent of
material
LAIV or recombinant QIVs may be best for safety and
immunogenicity.
Wheezing a possible issue.
Children with allergic reactions and asthma will need
exclusion.
Lab issues and pharmacopoeial
Extra SRIDs and calibrations on an already stressed
system.
The Bs seem to interfere with each other in lab tests
Adjuvants are v difficult
The upper fiducial limit will come into play for protein
Stability studies needed
Manufacturers.
They will need to start production before the
WHO rec is made and try and 2nd guess
2 strains.
A triple or quadruple Change one year there
will be practical difficulties.
SH more affected as time lines tighter.
Programme managers
Cost
If TIV and QIV out there will be marketing
issues
and perhaps conflicting advice.