Influenza Disease & Vaccination: Current Perspective with special
reference to India
Dr. Gaurav Gupta, Practising Pediatrician
Member AAP, IAP Charak Clinics, Mohali, Punjab
Influenza: An overview!
General introduction to influenza viruses and infection
Influenza outbreaks and pandemics
Analysis of pandemic H1N1
Defining at-risk populations
Influenza Vaccine – Data from Chandigarh
Influenza Vaccines Recommendations 2010-11 season
Influenza Vaccines Recommendations 2011-12 season
Influenza Vaccines
Influenza: An overview!
General introduction to influenza viruses and infection
Influenza outbreaks and pandemics
Analysis of pandemic H1N1
Defining at-risk populations
Influenza Vaccine – Data from Chandigarh
Influenza Vaccines Recommendations 2010-11 season
Influenza Vaccines Recommendations 2011-12 season
Influenza Vaccines
Influenza virus has several subtypes!
HA, hemagglutinin; NA, neuraminidase
Different influenza A subtypes result from differentcombinations of the HA and NA proteins
Influenza is a member of the Orthomyxoviridae family of viruses
Influenza A and B cause seasonal epidemics, C mainly causes mild respiratory illness
Influenza A is divided into subtypes based on the HA and NA proteins
HA and NA genes can be reassorted (switched) between strains generating novel subtypes
H1N1
H1N2
H2N1
H2N2
Orthomyxoviridae family
A 16 HA proteins
9 NA proteins
B
C
H1
H2
N1
N2
Influenza infection has a variety of symptoms!
Clinical symptoms Influenza infections are asymptomatic in
30–50% of cases
Common symptoms include abrupt onset of fever (38–40°C), sore throat, unproductive cough, runny or stuffy nose, headache, myalgia, chills, anorexia and extreme fatigue
Uncommon symptoms include photophobia, abdominal pain and diarrhea
Illness improves in under 7 days, cough and malaise may persist for weeks
Children may experience high fevers that can lead to febrile seizures
Fever may be absent in the elderly; presenting signs may include anorexia, lassitude or confusion
Influenza virus particles (brown) invade cilia (blue) in the airways
Virus shedding Adults: from the day before symptoms appear
until 5 days after illness onset
Young children: several days before illness onset until >10 days afterwards
Severely immunocompromised patients: weeks to months
Symptoms associated with seasonal influenza are well defined and can vary between individuals
Zambon MC. J Antimicrob Chemother 1999; 44 (Suppl. B):3-9; CDC, Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2007. MMWR Recomm Rep 2007; 56:1-54.
Clinical Differentiation Between the Common Cold
and the Flu
The following symptoms are more commonly seen in influenza rather than the common cold:• High fever lasting 3 to 4 days
• Headache
• Myalgia
• Fatigue and weakness
• Extreme exhaustion
• Severe chest discomfort and cough
The following symptoms are more commonly seen in the common cold rather than influenza:• Stuffy nose is common
• Sneezing is common
• Cough is generally mild to moderate
• Symptoms such as fever, headache, aches and pains and exhaustion are rare in those with colds.
Influenza viruses are spread by virus-laden aerosols!
How influenza viruses are spread: From person to person primarily through
large-particle respiratory droplet transmission
• Requires close contact betweensource and recipient as droplets only travel <1m
By contact with surfaces contaminated with respiratory droplets
By airborne transmission of evaporated droplets that may remain in the air for long periods of time (data are limited)
Virus transmission may be slowed by social distancing
CDC, Epidemiology and prevention of vaccine-preventable diseases. Atkinson W, Hamborsky J, McIntyre L, Wolfe S, eds. 10th ed. Washington DC: Public Health Foundation; 2007:235-56; Rust MJ, et al. Nat Struct Mol Biol 2004; 11:567-573; CDC, Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2007. MMWR Recomm Rep 2007; 56:1-54.
Influenza: An overview!
General introduction to influenza viruses and infection
Influenza outbreaks and pandemics
Analysis of pandemic H1N1
Defining at-risk populations
Influenza Vaccine – Data from Chandigarh
Influenza Vaccines Recommendations 2010-11 season
Influenza Vaccines Recommendations 2011-12 season
Influenza Vaccines
Influenza virus changes due to antigenic drift or shift!
Antigenic drift occurs when there are small changes in the virus
Antigenic drift produces new virus clades that may not be recognized by the immune system, meaning reinfection can occur
Drifted strains may be mismatched with seasonal influenza vaccine
Antigenic shift is a major change in the influenza A virus, altering the HA and/or NA proteins
Antigenic shift leads to the emergence of a new influenza A subtype
Most people have little or no protection against the new virus
Antigenic drift
NAHA
A/H1N1
Antigenic shift
A/H3N2
A/H1N2
Geneticressortment
Antigenic drift can lead to epidemics; antigenic shift can lead to pandemic influenza
Geneticmutations
Cox NJ, Subbarao K. Annu Rev Med 2000; 51:407-421; Zambon MC. J Antimicrob Chemother 1999; 44 (Suppl. B):3-9; Koelle K, et al. Science 2006; 314:1898-1903.
A/H1N1A/H3N1
NAHA
Influenza pandemics & emerging new pandemic threats exist since 1900!
The emergence of H1N1 has demonstrated the difficulty in predicting pandemicsNicholson KG, Wood JM, Zambon M. Lancet 2003; 362:1733-1745; WHO, Cumulative number of confirmed human cases of avian influenza A/(H5N1), available at: http://www.who.int/csr/disease/avian_influenza/country/cases_table_2008_09_10/en/index.html (accessed 5 November 2008); CDC, Avian Influenza, available at: http://www.cdc.gov/flu/avian/outbreak.htm (accessed 5 November 2008).
Pandemic outbreaks Recent outbreaks of influenza
1918 1957 1977 2000 2008
>50 million deaths
H1N1
1918Spanish
1957Asian
~2 million deaths
H2N2
1968Hong Kong
~1 million deaths
H3N2
<1 million deaths
H1N1
1977Russian
H9N2
1999Hong Kong
2 cases
H5N1
1997Hong Kong
18 cases
Six
deaths
H7N7
82 cases
One death
H5N1
2003-2008
Global
387 cases
245 deaths
2003Dutch
1968
H1N1
2009Global
~30,000 cases
145 deaths
2009
Pandemic
The circulation of H5N1 in poultry and its high fatality rate have raised concerns over an H5N1 pandemic if this virus acquires the capacity for sustained human-to-human transmission
Transmission dynamics are described using the reproductive number (R0) and case fatality ratio, which may vary depending on country and season
Influenza: An overview!
General introduction to influenza viruses and infection
Influenza outbreaks and pandemics
Analysis of pandemic H1N1
Defining at-risk populations
Influenza Vaccine – Data from Chandigarh
Influenza Vaccines Recommendations 2010-11 season
Influenza Vaccines Recommendations 2011-12 season
Influenza Vaccines
Emergence of Swine Flu Virus
Human virusHuman virus
Avian virusAvian virusAvian
ReservoirAvian Reservoir
New ReassortedvirusNew Reassortedvirus
SwineSwine
Other mammals?Other mammals?
START
March 2009
1-10
11-50
51-500
>500
Cumulative cases
April 2009
Pandemic H1N1 rapidly spread worldwide: April 2009
The H1N1 pandemic was first reported by the US and Mexico on 26 April 2009 Phase 4 of pandemic alert was declared on 27 April, and Phase 5 on 29 April By 30 April, 257 cases including eight deaths had been reported in 11 countries
WHO, H1N1 number of laboratory confirmed cases, available at http://gamapserver.who.int/h1n1/atlas.html (accessed 30 April 2009); WHO, H1N1 cases, situation update 6, available at http://www.who.int/csr/don/2009_04_30_a/en/index.html (accessed July 2009).
START
March 2009
April 2009
May 2009
Pandemic H1N1 rapidly spread worldwide: May 2009
* Date of last report for May 2009. WHO, H1N1 number of laboratory confirmed cases, available at: http://gamapserver.who.int/h1n1/atlas.html (accessed 29 May 2009); WHO, H1N1 cases situation update 41, available at http://www.who.int/csr/don/2009_05_29/en/index.html (accessed July 2009).
29 May *, 15,510 cases including 99 deaths reported by 53 countries
1-10
11-50
51–500
500-5,000
Cumulative cases
>5,000
Pandemic Influenza : Status in 2010
http://www.who.int/csr/don/2010_07_09/en/index.html
Influenza virological Surveillance (ILI) from 1st week Dec 2010 till now
http://gamapserver.who.int/GlobalAtlas/sharedFunction/sharedFunctionInterface.asp?displayType=map
Influenza : % positive cases & virus subtypes
http://www.who.int/csr/don/2010_07_09/en/index.html
Influenza: An overview!
General introduction to influenza viruses and infection
Influenza outbreaks and pandemics
Analysis of current pandemic H1N1
Defining at-risk populations
Influenza Vaccine – Data from Chandigarh
Influenza Vaccines Recommendations 2010-11 season
Influenza Vaccines Recommendations 2011-12 season
Influenza Vaccines
In hospitalized children:
• Febrile seizures reported by 6-20%1
• Intensive care required by 4-11%1
• 80% were <5 years of age; 27% were <6 months of age1
Exacerbation of underlying chronic pulmonary and cardiovascular diseases3
Complication rate higher for subjects with chronicheart disease (46.9%) vs. those without (22.8%)4
Infection rates for seasonal influenza are highest among children1
Elderly are at high risk of complications from seasonal influenza
Cumulative hospitalization rates for laboratory-confirmed influenza among children 0-4 and 5-17 years of age, by season, US2
Annual rates of influenza-associated cardiorespiratory hospitalizations in those ≥50 years of age, US5
Age (years)
Ho
sp
ita
liza
tio
n r
ate
pe
r 1
0,0
00
pe
rso
n-y
ea
rs
50-64 65-69 70-74 75-79 80-840
200
400
600
800
1,000
Po
pu
lati
on
-ba
se
d r
ate
40 42 44 46 48 50 52 2 4 6 8 10 12 14 16 18
Week
1
2
3
4
5
2004-05 0-4
2005-06 0-4
2006-07 0-4
2007-08 0-4
2004-05 5-17
2005-06 5-17
2006-07 5-17
2007-08 5-17
0
1. CDC, 2010 Yellow Book, available at http://wwwn.cdc.gov/travel/yellowbook/2010/chapter-2/influenza-seasonal-avian-pandemic.aspx (accessed August 2009). 2. CDC, Mortality and Morbidity Weekly Report 2009; 58:369-374. 3. Bridges CB, et al. Inactivated influenza vaccines. In: Plotkin SA, Orenstein WA, Offit PA, eds. Vaccines. 5th ed. Philadelphia: Saunders; 2008. 4. Irwin DE, et al. BMC Health Serv Res 2001; 1:8. 4. Thompson WW, et al. JAMA 2004; 292:1333-1340.
Season Age range (years)
Seasonal Influenza : elevated risk for complications is associated with both age extremes!
The majority of pandemic H1N1 cases have occurred in subjects <20 years of age!
1. Molinari NA, et al. Vaccine 2007; 25:5086-5096. 2. ECDC Surveillance Report, Analysis of Influenza A(H1N1)v individual case reports in EU and EEA countries, Update 9 July 2009. 3. WHO, Current WHO phase of pandemic alert, available at http://www.who.int/csr/disease/avian_influenza/phase/en/ (accessed July 2009).
Age distribution and travel status of pandemic H1N1 2009 cases in EU and EEA countries2
H1N1 pandemic influenza is predominantly found in patients <20 years of age; in contrast, the very young and the elderly are most at risk from seasonal influenza
The high level of domestic cases indicates community-level spread of the virus, meeting the WHO criteria for Phase 6 pandemic alert3
Seasonal influenza attack rates and proportionof population at high risk of serious complications, by age (US)1
N=7,681 cases reported by 28 EU/EEA countries as of 6 July 2009
0
10
20
30
40
50
60
0-4 5-17 18-49 50-64 65+
Age group
Pro
po
rtio
n o
f p
op
ula
tio
n (
%)
Gross attack rate
At high risk ofserious complications
Higher incidence of pandemic H1N1 than seasonal influenzain age group 10-19 years
≥6050-5940-4930-3920-2910-190-9
Domestic Travel related
2,500
2,000
1,500
1,000
500
0
Nu
mb
er o
f ca
ses
Age group
Age sex pattern of H1N1 cases in India
http://mohfw-h1n1.nic.in/documents/PDF/EpidemiologicalTrendsInIndia.pdf
Win – Win Situation vaccinating Pregnant Women
ACIP/ CDC/ ACOG recommend Flu vaccination during pregnancy
Can be done at any gestational age, earlier the better.
Benefits mothers by reducing serious respiratory infections during pregnancy
Benefits fetus – Better weight gain & decreased incidence of SGA
Benefits infant – the most effective way to prevent influenza in the first 6 months of life.
Influenza: An overview!
General introduction to influenza viruses and infection
Influenza outbreaks and pandemics
Analysis of current pandemic H1N1
Defining at-risk populations
Influenza Vaccine – Data from Chandigarh
Influenza Vaccines Recommendations 2010-11 season
Influenza Vaccines Recommendations 2011-12 season
Influenza Vaccines
Methodology-Clinical Effectiveness Study
• Prospective Observational Cohort Study• Vaccinated cohort (n=170) vs. Unvaccinated
cohort (n=330)Study Design
• Healthy child, of either sex, above 6 months of
age up to 18 years of age
• No chronic illness except asthma
Inclusion criteria
• H/O hypersensitivity to eggs and chicken proteinsExclusion criteria
25
Methodology-Clinical Effectiveness Study
• Private outpatient pediatric setting(Charak Care
Clinics, Mohali)Study site
• September, 2010 to May, 2011Study period
• Poisson regression analysis and Unpaired t-test for Risk ratio & statistical significance.
Statistical Analysis
26
Continued…..
Methodology-Clinical Effectiveness Study
• First call after 45 days of first dose of vaccine
then every month
Follow up Protocol
• Standard Predefined Data Form used. • Parameters measured –
ILI, Absenteeism, ARI, Unscheduled Physician visits
Data Collection
27
Continued…..
Overall Results
Vaccinated (198) vs Unvaccinated Cohort (397)
# Parameter RR CIp value
VE (%)
1 ILI0.65 0.49-0.84 0.001 35
2 ARI0.98 0.96-1.01 0.88
3 Unsch. Visit0.75 0.52-0.99 0.003 25
4Absenteeis
m0.97 0.70-1.32 0.86
Clinical Effectiveness of Influenza vaccine-1
Sr.No
Parameters Odds Ratio CI VE % P-value
1 Influenza like illness
0.58 0.24-0.92 42 0.009
2 Visits to Physician 0.71 0.33-1.09 29 0.039
Fully vaccinated cohort (n=154) vs. Unvaccinated cohort (n=330)*
Conclusion: Influenza vaccine is effective in reducing the ILI and visits to physician for ARI in fully vaccinated Indian children as compared to unvaccinated children.
*Renuka R, Gupta G, Tiwari P. Clinical effectiveness of the 2010-2011 seasonal influenza vaccine among healthy Indian children. WSPID-2011, Melbourne.
Clinical Effectiveness of Influenza vaccine-2
Sr.No Parameters Odds Ratio CI P-value
1 Influenza like illness 0.69 0.39-0.99 0.20
2 Visits to Physician 0.64 0.29-1.01 0.64
Partially vaccinated cohort (n=16) vs. Unvaccinated cohort (n=330)*
Conclusion: Partially vaccinated children had no significant protection against ILI and visits to physician as compared to unvaccinated children.
*Renuka R, Gupta G, Tiwari P. Clinical effectiveness of the 2010-2011 seasonal influenza vaccine among healthy Indian children. WSPID-2011, Melbourne.
Clinical Effectiveness of Influenza vaccine-3
Sr.No
Age group (no.) Odds Ratio
CI P-value VE %
1 6 m – 3 y (78) 0.57 0.46-1.31 0.55
2 3 y – 9 y (64) 0.48 0.17-0.72 0.002 52 %
3 9 y – 18 y (28) 0.69 0.39-1.03 0.06
Age-wise efficacy for prevent of ILI*
Conclusion: Children aged 3-9 year had the best protection rates against ILI as compared to unvaccinated children.
*Renuka R, Gupta G, Tiwari P. Clinical effectiveness of the 2010-2011 seasonal influenza vaccine among healthy Indian children. WSPID-2011, Melbourne.
Comparative Vaccine Effectiveness
Fully vaccinated (154) vs Unvaccinated Cohort (330) (2010-11)
# Parameter RR CI p value VE (%)
1 ILI 0.65 0.48-0.86 0.003 35
2 Unsch. Visit 0.74 0.51-0.99 0.007 26
Fully vaccinated (101) vs Unvaccinated Cohort (141) * (2009-10)
# Parameter RR CI p value VE (%)
1 ILI 0.57 0.32-0.09 0.05 43
2 Unsch. Visit 0.43 0.22-0.09 0.007 57
* Singh H, Gupta G, Tiwari P. Clinical effectiveness of the 2009-2010 seasonal influenza vaccine among healthy Indian children. ISPOR 4th Asia Pacific Conference, Phuket, Thailand.
Safety and Tolerability of Influenza vaccine-1
Inj. s
ite te
nderness
Fever
Cough/ cold
Runny nose
Sore th
roat
Vomitin
g
Irrita
bility
Diarrh
ea
Abdomin
al pain
Absente
eism
Unschedule
d visi
ts
Serious
side e
ffect
02468
101214161820 18
11.3
8
5.5
2.2 2.6
5.5
2.91.1
4.7
10.2
0
Percentage
Primary and secondary parameters(N=272)
Percentage
Singh H, Gupta G, Tiwari P. Safety and tolerability of trivalent inactivated influenza (TIV) vaccine in healthy Indian children. 62nd Indian Pharmaceutical Congress, 2010. Manipal, India. (Poster No. L-6).
Safety and Tolerability of Influenza vaccine-2
*Singh H, Gupta G, Tiwari P. Safety and tolerability of trivalent inactivated influenza (TIV) vaccine in healthy Indian children. 62nd Indian Pharmaceutical Congress, 2010. Manipal, India. (Poster No. L-6).
MIL
D
MO
DE
RA
TE
SE
VE
RE
MIL
D
MO
DE
RA
TE
SE
VE
RE
Local reactions (Inj. site tenderness) Systemic reactions
05
101520253035404550
5.92.2
0
16.4
8.9
0
19.5
41.6
8.94.8 4
46.6
0 0
6.6
0
6.6
> 6 to 35 Months
3Y to 9Y
> 9Y
Grading of the reactions after vaccinationN=272
Percentage
Pandemic influenza: An overview!
General introduction to influenza viruses and infection
Influenza outbreaks and pandemics
Analysis of current pandemic H1N1
Defining at-risk populations
Influenza Vaccines Recommendations 2010-11 season
Influenza Vaccines Recommendations 2011-12 season
Influenza Vaccines
Influenza Vaccines are representative of virus strains circulating in India as well
WHO Influenza Global Surveillance Networko The network was established in
1952
o Currently, WHO have 128 institutions from 99 countries as recognized National Influenza centers
Objectives:
Surveillance enables to recommend twice the content of Influenza vaccine for the season
Serves as a global alert mechanism for the emergence of Influenza virus with Pandemic potential
1 Laboratory
≥ 2 Laboratory
No Laboratory
AIIMS
NICED Kolkata
Chennai
RMRC Dibrugarh
PuneMumbai
V P Chest
New Delhi
IGGMCNagpur
CMCVellore
Regional CentersNew CentersReferral Center
Haffkine Inst
NIV
KIPM
Pandemic Flu protection added to Seasonal flu vaccine
WHO Influenza strain for Northern Hemisphere 2010 – 2011 season:
• an A/California/7/09 (H1N1)-like virus; *
• an A/Perth /16/2009 (H3N2)-like virus; **
• a B/Brisbane/60/2008-like virus.***
*A/California/7/09 (H1N1)-like virus is the pandemic (H1N1) 2009 influenza virus. A monovalent vaccine containing this strain was made available to the United States in the fall of 2009.
**A/Perth/16/2009 (H3N2)-like virus is a change from the 2009-2010 influenza vaccine formulation.
***and B/Brisbane /60/2008-like virus is a current vaccine virus.
http://www.who.int/csr/disease/influenza/recommendations201010north/en/
ACIP Recommendations for seasonal Influenza vaccination 2010-11
1. A recommendation that annual vaccination be be administered to every individual aged ≥6 months for the 2010-11 influenza season
2. Children and adolescents at higher risk for influenza complications
• ! Are aged 6 months–4 years (59 months);
• ! Have chronic pulmonary, cardiovascular, renal, hepatic, cognitive, neurologic/neuromuscular,
• hematological or metabolic disorders (including diabetes mellitus)
• ! Are immunosuppressed (Caused by medications or by HIV)
• ! Are receiving long-term aspirin therapy and therefore might be at risk for experiencing Reye syndrome after influenza vaccination
• ! Are residents of long-term care facilities; and
• ! Will be pregnant during the influenza season.
Source: CDC recommendation available at http://www.cdc.gov/flu
Pandemic influenza: An overview!
General introduction to influenza viruses and infection
Influenza outbreaks and pandemics
Analysis of current pandemic H1N1
Defining at-risk populations
Influenza Vaccines Recommendations 2010-11 season
Influenza Vaccines Recommendations 2011-12 season
Influenza Vaccines
WHO Recommended strains 2011 -12 season
It is recommended that vaccines for use in the 2011-2012 influenza season (northern hemisphere) contain the following:
an A/California/7/2009 (H1N1)-like virus;
an A/Perth/16/2009 (H3N2)-like virus;
a B/Brisbane/60/2008-like virus.
2011-12 season WHO recommended strain are similar to 2010-11 season northern hemisphere strains
2009
-10
2010
-11
2011
- 12
Brisbane
Brisbane
Brisbane
BA/H3N2
A/H1N1
California
Perth
Brisbane
1. www.who.int; 2. http://www.fda.gov/cber/flu/flu2008.htm.
Influenza Season (year)
Drift has led to 15 changes in recommended strains since 1997-19981,2
1997
-98
2007
-08
1999
-00
1998
-99
2000
-01
2001
-02
2002
-03
2003
-04
2004
-05
2005
-06
2006
-07
2008
-09
Bayern
Wuhan
Beijing New Caledonia SolomonIslands
Sydney Moscow FujianCalifornia Wisconsin
Beijing Sichuan Hong Kong Shanghai Malaysia
Brisbane
Brisbane
Florida
BA/H3N2A/H1N1
WHO monitors strain drifts and recommends strains for vaccine inclusion
For the Northern hemisphere, the recommended strains have changed 12 times since 1997-1998
Key Questions
Question 1
Is annual vaccination reqd. if the strain remains the same for consecutive years?
Yes, we require annual Influenza Vaccination if vaccine strains remain the same which is well supported by:
• Local guidance
• International guidance
• Guidance from a standard textbook
Key Questions
Question 2
What is the best time to give the Influenza vaccine in India?
Northern hemisphere
Southern hemisphere
Tropics
Influenza activity peak: November-March2,3
1. Bridges et al. 2008; 2. EISS 2004; 2. Cox and Subbarao 2000; 4. CHP 2008; 5. Yohannes et al. 2003.
Globe image: www.phimap.com
Influenza activity peak: April-September4,5
Year-round activity3,4
0
2
4
6
8
10
1 3 5 7 9 11 13 15 40 42 44 46 48 50 52Week
0
10
20
30
40
50
J F M A M J J A S O N D
Month
ILI/1
000
Po
pu
lati
on
ILI/1
000
Po
pu
lati
on
20
0
4
8
12
1618
2
6
10
14
1 5 9 13 17 21 25 29 33 37 41 49Week
45
ILI C
on
sult
atio
ns/
1000
Po
pu
lati
on
Influenza spread occurs inseasonal patterns
ILI = influenza-like illness.
E.g. India
Pandemic influenza: An overview!
General introduction to influenza viruses and infection
Influenza outbreaks and pandemics
Analysis of current pandemic H1N1
Defining at-risk populations
Influenza Vaccines Recommendations 2010-11 season
Influenza Vaccines Recommendations 2011-12 season
Influenza Vaccines
How Influenza vaccines are made
o The network was established in 1952
o Currently, WHO have 128 institutions from 99 countries as recognized National Influenza centers
Objectives:
Surveillance enables to recommend twice the content of Influenza vaccine for the season
Serves as a global alert mechanism for the emergence of Influenza virus with Pandemic potential
http://www.who.int/csr/disease/influenza/surveillance/en/index.html
WHO Influenza Global Surveillance Network
1 Laboratory
≥ 2 Laboratory
No Laboratory
Seasonal influenza vaccines are trivalent vaccines derived from the three viral types that are currently in global circulation
Types of Influenza Vaccines
A) whole-virus, B) split-virion, C) subunit, D) virosomal, E) adjuvanted.
Amorij JP, Huckriede A, Wilschut J, Frijlink HW, Hinrichs WL. Development of stable influenza vaccine powder formulations:
Challenges and possibilities. Pharm Res. 2008;25(6):1256-1273.
Live Attenuated Influenza Vaccine
Inactivated Influenza Vaccine Whole virus vaccines Split-virion Vaccine Subunit vaccine Adjuvanted vaccines Virosomal vaccines Cell culture derived vaccines
Comparison of Influenza Vaccines
Vaccine type Composition Immunogenicity Reactogenecity
Whole-virus (no longer used)
Whole virus +++ +++
Split-virion Surface proteins, nucleocapsid and matrix proteins
++ ++
Subunit Surface proteins ++ +
Virosomal Surface proteins plus virosomes
++ +
Adjuvanted Surface proteins plus adjuvant
+++ ++
Intradermal (subunit)
Surface proteins +++ ++
+Low; ++ Medium; +++ High.
Live vs Inactivated Influenza Vaccine
http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5213a1.htm
Thank You