Immunogenicity – i.e. immune response generated in the mother. Transfer of antibodies to fetus Split –Vision Vaccine Clinical efficacy in mother Clinical efficacy in newborn ( up to 6 months of age )

1. EFFECTIVENESS
OF
THE
INFLUENZA
VACCINE
Dr. Sharda Jain

2. Chairman & founder :-
Consultant : Max Hospital , Vashali, Founder chairman & Advisor
Former : Advisor Health National Commission for Women (2004-2007) -
Chairperson : Women Wing , IMA (2004-2007)
Member : Resources Committee NACO (2008-2011)
Dr. Sharda jain
ISO 14001:2004 (EMS)
…..Caring hearts, healing hands
ISO 9001:2008 ISO 9001:2008
Sec General :
Delhi Gynae Forum
LIFE TIME ACHIEVEMENT AWARDS
•FOGSI & ICOG(2016 )
•Delhi Gynaecologist Forum (2009)
•Lady Harding Medical Collage (2015)
•Delhi ISAR ( March 2016)
“Excellence Award in Medical
Services” by IMA 2016 .
2006 : SOUTHEAST ASIAN PARIAMENT
AWARD for outstanding work on Aneamia in
women & children
2008 : Received prestigious Lucy Omen
Award for contribution in women & girl child
health
“INDIA’S MOST EMINENT WOMEN AWARD
‘2015”
•Crusader against FEMALE FETICIDE
movement in the country by ALL INDIA
COUNCIL OF HUMAN RIGHT, LIBERTIES &
SOCIAL JUSTICE (2015 Dec.)
• Crusader against FEMALE FETICIDE , by
Gynae Endocrinology Association 2015

4. Questions :
Do we agree that the immunogenicity of the vaccine in
pregnancy is similar to the non-pregnant state ?
Do we agree that the maternal antibodies are adequately
transferred to the fetus to ensure protection?
Do we agree that the inactivated influenza vaccine has a
proven clinical effectiveness in protecting both mother and
newborn from Influenza related adverse outcomes?
Does the level of protection justify the use of IIVs in all
pregnancy women irrespective of the trimester ?
Do we agree that when both are available , the split-virion
influenza vaccine should be given priority over the subunit
Vaccine ?

5. Effectiveness of vaccine can be judged in 4
ways
1. Immunogenicity – i.e. immune
response generated in the
mother.
2. Transfer of antibodies to fetus
3. Clinical efficacy in mother
4. Clinical efficacy in newborn
5. ( up to 6 months of age )

6. 1- IMMUNOGENICITY of vaccine in
pregnancy
Immunogenicity is usually measured by titers of antibodies such as:
1. Hemagglutinin Inhibition (HI) titer, which measures the
concentration of antibody required to prevent influenza from
agglutinating red blood cells.
Thus, the HI titer is a measure of the total amount of antibodies to the
hemagglutinin (HA) protein . It is usually calculated as a geometric
mean of all values – hence known as Geometric mean titer .( GMT )
The WHO defines a “protective” titer as 1:40, based on a 50%
reduction in disease, and thus the term seroprotection refers to those
individuals with a titer of 1:40 or better.
This is the “ gold standard “ technique .

7. 1- IMMUNOGENICITY of vaccine in
pregnancy
2.The other technique used is Virus micro
neutralization (VMN) assay. This assay measures the
functional capability of antibodies at a specific dilution
rather than just the total quantity.
Multiple studies have demonstrated good correlation
between HI titers and VMN titers in pregnant women
following monovalent H1N1 and seasonal influenza
vaccination.

8. Studies on Immunogenicity and effectiveness
of vaccine in pregnancy
In 2008, Zaman et al , a large randomized-controlled trial (n= 340 )
of vaccination in pregnant women in Bangladesh demonstrated
that influenza vaccination was clinically efficacious in preventing
Influenza in pregnant women and their infants.
The immunogenicity data released in 2010 showed that the
pregnant women had significant increase in their GMTs to the
H1N1 , H3N2 and influenza B strains following vaccination and
seroconversion rates of
83.6% for H1N1 , 69.2% for H3N2 , and 39.7% for B influenza
strains
which are similar to those seen among healthy adults receiving
seasonal influenza vaccination.

9. Demonstrates protective titers of antibodies in both mother and infants up to age
of 6 months . ( Point 1 and 2 of effectiveness proved )
Benefits of influenza vaccination in pregnant
women and newborns- Zaman et al
Steinhoff MC, et al. Influenza immunization in pregnancy—antibody responses in mothers and infants. N Engl J Med 2010;362:1644-6.

10. Mother’s gift trial, Zaman et al , Bangladesh
Vaccine effectiveness: ( Point 3 and 4 of effectiveness
proved )
Maternal TIV DECREASED respiratory illness with fever:
29% among infants;
36% among their mothers.
Reduced proven influenza illness by 63% in infants up to
6 months of age
Zaman, K., et al., Effectiveness of maternal influenza immunization in mothers and infants. The New England journal
of medicine, 2008. 359(15): 1555-64.

11. Studies to demonstrate IMMUNOGENICITY
of vaccine in pregnancy
Ohfuji et al enrolled 150 pregnant women receiving the pH1N1
(15 μg) vaccination during pregnancy.
Immune responses were tested by HI titers 3 weeks after the
first dose .Robust responses were noted to the vaccination , with
an average HI antibody increase of more than 10-fold and a
sero-conversion rate of 91%.
Sperling et al performed a large multi-year study of 239
pregnant or postpartum women vaccinated with the seasonal
influenza vaccine between October 2006 and January 2010.
The timing of vaccination during pregnancy did not significantly
alter HI GMT .Seroprotection for H3N2 ranged from 65 to 95%
and for H1N1 from 75 to 98%,

12. Studies to demonstrate IMMUNOGENICITY
of IIV in pregnancy
Kay et al. assessed the induction of plasmablasts i.e. antibody-
secreting , activated B cells, in pregnant and non-pregnant
women relying on data collected in the 2010–2011 ,2011–2012,
and 2012–2013 seasons.
Pregnant women had a significantly greater induction of
plasmablasts following vaccination than the non-pregnant
controls (p=0.03).
All these studies show that in spite of the immune tolerance in
pregnancy , the immunogenic response to the Inactivated
Influenza vaccine is unaffected and is equivalent to that in the
non-pregnant state .

13. Englund et al. 13 women in 3rd trimester given TIV (vs TT). 1993
TRANSFER OF ANTI-BODIES from Vaccinated
mothers to fetus
Englund JA, et al. Maternal immunization with influenza or tetanus toxoid vaccine for passive antibody protection
in young infants. J Infect Dis. 1993 Sep;168(3):647-56.

14. ANTIBODY TRANSFER TO FETUS during
pregnancy
In2009, Tsatsaris et al. evaluated cord-blood titers and found that
maternal and cord- blood titers correlated(r =0.86) for HI after
maternal IIV vaccination in pregnancy .
Thus the transfer of antibodies from mother to fetus results
in robust HI titers in the fetus irrespective of the gestational
age at which the mother is vaccinated .
Infant titers of 1:40 or greater were observed in 95% of the 88
cord-blood samples tested, and cord-blood titers were
significantly higher than maternal blood titers.
Neither gestational age at vaccination nor delivery
significantly affected the neonatal seroprotection rates.
Similar results were obtained by another study -Jackson et al.

15. KEY STUDY on efficacy in mother – Madhi et
al
Vaccine / Years studied : Seasonal IIV , 2011-12 & 2012-13.
Study participants :2116 pregnant women were enrolled,1062 received
IIV, and 1054 received placebo. All trimesters included . HIV positive
subset was included.
Immune assays and outcomes : HI titers pre-vaccination and 28–35 days
post-vaccination. Multiple influenza disease endpoints evaluated .
VACCINE RESPONSE : SEROPROTECTION TO H1N1 93.3%, H3N2 78.0%,
AND B 96%. OVERALL VACCINE EFFICACY OF PREVENTING CONFIRMED
INFLUENZA 54.4%.
SEROPROTECTION IN HIV-INFECTED WAS 48.6% H3N2 AND 68.6% H1N1,
BUT VACCINE EFFICACY WAS 70.6% IN THIS SUBSET .

16. Key studies on efficacy of maternal Influenza
vaccination
Study : Lin et al. (2013)
Study participants :pregnant: 46 more than 18 years old more
than 20 weeks' gestation.
Seroprotection rates (HI antibody titer > 1:40) against H1N1,
H3N2, and B were 91.3%, 84.8, and 56.5% at 28 days after
vaccination, respectively.
Fold increases in geometric mean titer against H1N1, H3N2,
and B were 12.8-, 8.4- and 4.6-fold at 28 days after
vaccination, respectively.

17. Clinical Efficacy of maternal vaccination :
Improved Maternal and Fetal outcomes
Steinhoff MC, et al. Influenza immunization in pregnancy—antibody responses in mothers and infants. N Engl J Med 2010;362:1644-6.
McNeil, S.A., et al., Effect of respiratory hospitalization during pregnancy on infant outcomes. American journal of obstetrics and gynecology, 2011. 204(6 Suppl 1): p. S54-7.
Omer, S.B., et al., Maternal influenza immunization and reduced likelihood of prematurity and small for gestational age births: a retrospective cohort study. PLoS medicine, 2011. 8(5): p.
e1000441.
Anderson, B.L., D.J. Rouse, and C. Fitzsimmons, Clinical characteristics of pregnant women with influenza-like illness during the 2009 H1N1 pandemic and use of a standardized
management algorithm. American journal of obstetrics and gynecology, 2011. 204(6 Suppl 1): p. S31-7.

18. Clinical Efficacy of IIVs in pregnancy
Zaman, K., et al., Effectiveness of maternal influenza immunization in mothers and infants. The New England journal of medicine, 2008. 359(15):1555-64.
Poehling, K.A., et al., Impact of maternal immunization on influenza hospitalizations in infants. American journal of obstetrics and gynecology, 2011. 204(6 Suppl 1):S141-8.
Eick, A.A., et al., Maternal influenza vaccination and effect on influenza virus infection in young infants. Archives of pediatrics & adolescent medicine, 2011. 165(2):104-11.
Benowitz, I., et al., Influenza vaccine given to pregnant women reduces hospitalization due to influenza in their infants. Clinical infectious diseases : an official publication of the Infectious
Diseases Society of America, 2010. 51(12): 1355-61.

19. Studies Demonstrating
Clinical efficacy in infants
Benowitz et al. performed a matched case–control study with
case patients defined as infants under 12 months that were
admitted to the hospital due to laboratory-confirmed influenza
between October 2000 and April of 2009.
The adjusted vaccine efficacy was 91.5% in infants < 6 months
of age .

20. Figure
Source: The Lancet Infectious Diseases 2012; 12:658-659 (DOI:10.1016/S1473-3099(12)70184-6)
Influenza Vaccine Effectiveness
A Meta-analysis
• Median vaccine effectiveness against PCR-confirmed
influenza of 86%.
• Pooled vaccine effectiveness of 88%

21. There are 2 types of Inactivated Influenza
Vaccines having different efficacy …….

22. Split virion Vs Subunit( Surface)
Vaccines
What’s the difference ?

23. Introduction
Split –Virion Vaccine : Influenza viruses are grown in
pathogen-free medium, and the virus membrane is
disrupted with the use of a surfactant.
Subunit Vaccine : In addition to disruption of
membrane , here differing sedimentation technique is used
to remove the internal sub-viral core.

24. IMMUNE RESPONSES OF THE 2 VACCINES
There are 2 types of responses needed from body to clear Influenza virus
.
1.Cellular response
2.Antibody response
Split-virion vaccine shows both cellular and antibody response. Subunit (
surface ) shows only antibody response .
This is because the cellular response is triggered by internal proteins such
as nucleoprotein, polymerases, and matrix proteins.
SPLIT-VIRION VACCINE MAINTAINS THE INTERNAL PROTEINS WHEREAS
SUBUNIT VACCINE DOES NOT HAVE THE INTERNAL PROTEIN CORE .

25. SUPERIOR IMMUNE RESPONSE WITH
SPLIT- VIRION
Co et al reported that split-virion influenza vaccines stimulated a
stronger cellular immune response to influenza than subunit
vaccines using various techniques like –
1.Cr 51 radioactive assay
2.Western blot assay
3.Enzyme-linked immunospot assay (ELISPOT)
4.Intracellular cytokine staining (ICS)
5.Proteomic analyses ( analysis of influenza proteins)
Co et al proves that
cellular response is
stronger with split
virion !!

26. Clinical Effectiveness of Split-Virion Versus Subunit Trivalent
Influenza Vaccines in Older Adults . Major article . Talbot et al.
Published: CID ( Clinical Infectious Diseases) 2015:60 (15 April)
Strengths of the study :
1.Prospective
2.Adults aged ≥50 years
3.3 Influenza seasons: covered 2008–2009, 2010–2011, and 2011–2012
4.Control arm present
5.539 patients .( adequate sample size)
Results : Split-virion vaccine effectiveness was 77.8% compared with
subunit vaccine effectiveness of 44.2%
Conclusion : Vaccine effectiveness of Split Virion was 33.5% higher than the subunit
vaccine.
Clinically proven that split
virion is more effective than
subunit by 33.5% !!

27. Split Vaccine of Pasteur : A very good tolerability
profile
Comparison of reactogenicity of split vaccines and sub-unit vaccines,
in 16637 elderly people ( >65 years old) in a prospective study in Italy
In this study, Split vaccine
of Pasteur is better
tolerated than other split
vaccines and comparable
to or even better than
most of the sub-unit
vaccines
1-Spila-Alegiani S et al.
Reactogenicity in the elderly
of nine commercial influenza
vaccines: results from the
Italian SVEVA study.;

28. ISO 14001:2004 (EMS)
…..Caring hearts, healing
hands
ISO 9001:2008
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