Influenza vaccine is nothing new . However there are lesser known facts about Influenza vaccine. This is just a humble attempt to highlight a few important points about Influenza vaccine, including some updates. Burden of Influenza disease worldwide. Importance of Influenza vaccine in Corona virus pandemic. Influenza vaccine quadrivalent vs trivalent vaccine. Split virion vs Subunit influenza vaccine 0.5 ml dose of influenza vaccine below 3 yrs age in children Northern hemisphere or Southern hemisphere influenza vaccine for India, some suggestions

2. In COVID 19 era should we worry
about Influenza ?
• Health systems already overwhelmed by
SARS-CoV-2 pandemic
• Good coverage with Influenza vaccine will
preserve the capacity and function of health
systems
• Most of our surveillance systems pre
occupied with Corona virus pandemic , so
recent data may not be available

3. Recent exposure to Influenza virus might
worsen the outcome of COVID19
• ACE- 2 m-RNA upregulation in alveolar epithelial
cells after an Influenza virus infection.
• This may worsen the outcome of COVID 19
Hui KP et al, Lancet Resp Medicine July 2020
DOI:https://doi.org/10.1016/S2213-2600(20)30193-4

4. Inactivated influenza vaccine is associated with lower mortality
among Covid-19 patients in Brazil
• Data from 92,664 clinically and molecularly
confirmed Covid-19 cases in Brazil
• patients who received a recent influenza vaccine
experienced on average
- 8% lower odds of needing intensive care
treatment (95% CIs [0.86, 0.99]),
- 18% lower odds of requiring invasive respiratory
support (0.74, 0.88) and
- 17% lower odds of death (0.75, 0.89).
- Fink et al ,July 2020 doi:https://doi.org/10.1101/2020.06.29.2014250

5. Influenza burden

6. Influenza deaths summary

7. Meta-analysis of global burden in
children
Global incidence of and mortality was estimated worldwide in
children < 5 yrs of age in 20081
Source: Nair Lancet 2012 GLOBAL SYSTEMATIC REVIEW OF INFLUENZA BURDEN 1995- 2010 , Data
used to calculate burden in 2008
28,000-111,500 deaths
1 (1-2) million severe ALRI
20 (13-32) million cases of ALRI
90 (49-162) million cases of
influenza
ALRI=Acute Lower Respiratory Infections

8. Susceptible age groups

9. Attack rate higher in children,
More so for Influenza- B

10. AAJ KI TAAZA KHABAR

11. Sources: 1. Integrated Disease Surveillance Programme; Seasonal Influenza (H1N1)– State/UT- wise, Year- wise number of cases
and deaths from 2010 to 2017. Available from http://www.idsp.nic.in/showfile.php?lid=3933 ; accessed on 28th June 2018 .
2. Integrated Disease Surveillance Programme; Seasonal Influenza (H1N1)– State/UT- wise, Year- wise number of cases and
deaths from 2012 to 2019. Available from https://ncdc.gov.in/showfile.php?lid=280
Year
Cases (Lab
confirmed)
Deaths
2010 20604 1763
2011 603 75
2012 5044 405
2013 5253 699
2014 937 218
2015 42592 2990
2016 1786 265
2017 38811 2270
2018 15266 1113
2019 28798 1218
2020 (As on 23rd Feb
2020)
1132 18
I NDI A - SEASONAL I NF LUENZA CASES - 2 0 1 0 TO 2 0 1 9

12. Crux of the Influenza Scenario
• Significant Global burden
• Indian data show mortality around 4-8
percent in “reported cases”.
• Both A and B type Influenza viruses seen in
India in 2020 data
• Even though B type accounts for lesser
number of cases, it is more common in
children less than 5 yrs as compared to
adults.

13. • All persons 6 months and older should be
vaccinated annuallyCDC
• All healthy children 6-59 months
• All high risk children >6 months
• All school going children
ACIP
• All children between 6 months to 5 years of
age
Indian Academy
of Pediatrics
• Everyone 6 months and older,
including children and adolescents
American
academy of
pediatric
Influenza vaccine recommendation:
Pediatric age groups

14. Do we need QIV ?

15. Chadha, Mandeep S et al. “Multisite virological influenza surveillance in India: 2004-2008.”
Influenza and other respiratory viruses vol. 6,3 (2012): 196-203. doi:10.1111/j.1750-
2659.2011.00293.x

16. QIV needed since 2002?

17. What can be the extent of mismatch if TIV
( either Victoria or Yamagata lineage used)
Ambrose CS, Levin MJ. Hum Vaccin Immunother. 2012;8(1):81-88.
doi:10.4161/hv.8.1.17623

18. Does an extra B type in QIV really
matter?

19. For Naïve population QIV needed
Beyer et al.Vaccine 2017 July 24; 35 (33):4167-4176

20. Model predicts 27.2 % reduction in Influenza B cases with QIV
vaccine
e Boer PT, Crépey P, Pitman RJ, Macabeo B, Chit A, Postma MJ. Cost-Effectiveness of Quadrivalent
versus Trivalent Influenza Vaccine in the United States. Value Health. 2016;19(8):964-975.
doi:10.1016/j.jval.2016.05.012

21. Type B Influenza virus coverage is
important too!
Contrary to what is commonly assumed, the causal virus
subtype does not seem to be a major determinant of clinical
presentation and severity of influenza illness
Therefore, adequate coverage of B type Influenza viruses is
of paramount importance.
Caini S, Kroneman M, Wiegers T, El Guerche-Séblain C, Paget J.
Clinical characteristics and severity of influenza infections by
virus type, subtype, and lineage: A systematic literature
review. Influenza Other Respir Viruses. 2018;12(6):780-792.
doi:10.1111/irv.12575

22. Landmark study proving QIV better than TIV

23. Claeys et al. Lancet 2018

24. Phase 3 trial of subunit qiv – children
& adolescents
Source: Vesikari T et al. Immunogenicity and safety of quadrivalent versus trivalent inactivated subunit influenza vaccine in children and adolescents:
A phase III randomized study. Int J Infect Dis. 2019 Dec 12. pii: S1201-9712(19)30483-7.

25. Phase 3 trial of subunit qiv - children
& adolescents – summary
• 1200 subjects (children and adolescents 3–17 years of age) were
randomized to receive
- QIV (n = 402),
- TIV(Vic) (n = 404)
- or TIV(Yam) (n = 394).
Conclusions:
• QIV immunogenicity comparable to TIV for shared-lineage influenza
strains & superior to TIV for alternate-lineage influenza B-strains
• Inclusion of a second B-strain lineage does not compromise safety
Source: Vesikari T et al. Immunogenicity and safety of quadrivalent versus trivalent inactivated subunit
influenza vaccine in children and adolescents: A phase III randomized study. Int J Infect Dis. 2019 Dec 12.
pii: S1201-9712(19)30483-7.

26. Whole virus
vaccine (1945)
Split virus vaccine
(1964)
3rd generation
1st generation
2nd generation
Subunit vaccine (1976)
1. Wood JM, Williams MJ. Textbook of Influenza 1998; pg no 317-323.
2. Shah R et al. Asian Journal of Paediatric Practice. 2018; 1(5): 19-28.
Historical Development in
Influenza Vaccination
SUV presents better tolerability and lower
reactogenicity as compared to other vaccine types

27. Comparison of immunogenicity of Subunit (SU) vs
Split vaccine(SPL)
GMR, geometric mean ratio; SPL, split-virus vaccine; SU, aqueous subunit vaccine; VIR, virosomal, subunit vaccine Beyer et al. Vaccine 2011

28. Comparison of local and systemic side effects of
Subunit (SU) vs Split vaccine(SPL)

29. H. Keipp Talbot et. al
Split-Virion vs Subunit Vaccine • CID 2015:60 (15 April)
Study which favours Split Virion Vaccine has
limitations
Insufficient sample size
Participants >50yrs ( no naïve population)
One small geographical area studied with
only one brand of split virion vaccine
More meta-analytical studies needed

30. • 0.50 ml induced a higher response than 0.25 ml for all strains
• Reactogenicity/safety endpoints were within the same range
Source: Pavia-Ruz N et al. A randomized controlled study to evaluate the immunogenicity of a trivalent inactivated seasonal influenza vaccine at two dosages in
children 6 to 35 months of age. Hum Vaccin Immunother. 2013; 9(9):1978-88.

31. Source: Wang L et al. Immunogenicity and Safety of an Inactivated Quadrivalent Influenza Vaccine in US Children 6-35 Months of Age During 2013-2014: Results
From A Phase II Randomized Trial. J Pediatric Infect Dis Soc. 2016 Jun;5(2):170-9.
• Compared inactivated QIV versus TIV (15 and 7.5 μg HA)
• QIV demonstrated immunogenic superiority over TIV for B strain not present in
TIV
• Safety was similar between the vaccine groups despite the QIV’s higher antigen
content

32. Time to change the dose of Flu vaccine
to 0.5ml for all children > 6 months?
Source: Jain VK et al. Time to Change Dosing of Inactivated Quadrivalent Influenza Vaccine in Young Children: Evidence From a Phase III, Randomized, Controlled
Trial. J Pediatric Infect Dis Soc. 2017 Mar 1;6(1):9-19.
Global Study-Compared 0.5 ml QIV with 0.25 ml QIV
in children 6 – 35 months
Conclusion: 0.5 ml QIV may improve protection against influenza B in some young
children and simplifies annual influenza vaccination by allowing the same vaccine
dose to be used for all eligible children and adults.

33. Seroconversion rate, Seroprotection rate, and Mean Geometric Increase
values were higher in the double-dose (0.5 ml) group compared with the
standard-dose (0.25 ml) group in children 6–35 months of age
Source: Jain VK et al. Time to Change Dosing of Inactivated Quadrivalent
Influenza Vaccine in Young Children: Evidence From a Phase III,
Randomized, Controlled Trial. J Pediatric Infect Dis Soc. 2017 Mar 1;6(1):9-
19.

34. Summary of results of 0.5 ml dosing of Influenza vaccine in
children < 36 months
• A 0.5 dose of QIV may offer greater protection
to children less than 3 years against Influenza B
in case of antigenic mismatch
• There is evidence to support change in clinical
practice, to use full dose ( 15 mcg) of QIV in
children 6 months and older
Jain VK, Domachowske JB, Wang L, et al. Time to Change
Dosing of Inactivated Quadrivalent Influenza Vaccine in Young
Children: Evidence From a Phase III, Randomized, Controlled
Trial. J Pediatric Infect Dis Soc. 2017;6(1):9-19.
doi:10.1093/jpids/piw068

35. Proprietary and confidential — do not distribute
Higher Immunogenicity Evidence of 0.5 ml qiv in children 6-35 months
Year
(Country)
Vaccines Used Vaccine Dose Results
2014-15
(US & Mexico)
Investigational QIV (GSK
Vaccines) & Fluzone
Quadrivalent (Sanofi Pasteur)
0.5 ml VS 0.25 ml
Single dose in primed
0.5 ml offers better protection
than 0.25 ml2
2013-14 (US) Investigational QIV (GSK
Vaccines) & licensed TIV
(Sanofi Pasteur)
0.5 ml QIV VS 0.25 ml
TIV; Single dose in
primed
0.5 ml QIV was immunogenic with
acceptable safety1
2018
(Europe, Central
America, and Asia,
including India)
Quadrivalent vaccine
(GSK)
0.5 ml vs Non influenza
control; Single dose in
primed
QIV prevented influenza A and B in
children aged 6-35 months3
2018
(India)
Influvac Tetra (Abbott) 0.5 ml Single dose in
primed; 2 doses in
unprimed
Influvac® Tetra elicited an
adequate immune response in both
age groups and demonstrated a
favorable safety profile with
generally a low level of
inconvenience.4
Source: 1. Wang L et al. Immunogenicity and Safety of an Inactivated Quadrivalent Influenza Vaccine in US Children 6-35 Months of Age During 2013-2014: Results From A Phase II
Randomized Trial. J Pediatric Infect Dis Soc. 2016 Jun;5(2):170-9. 2. Jain VK et al. Time to Change Dosing of Inactivated Quadrivalent Influenza Vaccine in Young Children: Evidence
From a Phase III, Randomized, Controlled Trial. J Pediatric Infect Dis Soc. 2017 Mar 1;6(1):9-19. 3. Claeys C et al. Prevention of vaccine-matched and mismatched influenza in children
aged 6−35 months: a multinational randomised trial across five influenza seasons. Lancet Child Adolesc Health. 2018 May;2(5):338-349. 4. Influvac Tetra Synopsis (Data on file).

36. Since seroprotective correlates for Influenza are not
known it is seen that antibody titres (%) to HAI >40 In
adults and HAI >110 in children, offer 50 percent
protection from the disease. The desired value antibody
titres to HAI should be around 330 for optimal
protection, which is given by high dose vaccine

38. Global Recommendations & Guidelines
Source: 1. https://www.who.int/wer/2012/wer8747.pdf?ua=1 ; 2. https://www.cdc.gov/flu/pdf/professionals/acip/acip-2018-19_summary-of-recommendations.pdf ;
3. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/733840/Influenza_green_book_chapter19.pdf ;
WHO Position Paper (2012) 0.25 ml or 0.5 ml
CDC ACIP (2018-19) 0.25 ml or 0.5 ml
The Green Book (UK) (2017) 0.5 ml dose
Canadian Immunization Guide
Chapter
0.5 mL dosage
NSIG, New Zealand full 0.5 mL dose

39. Summary – 0.5 ml dose in
children 6-35 months
• Better immune response with 0.5 ml in
children 6-35 months, as evidenced in studies
• Global trend of using 0.5 ml (15 mcg/strain)
by guidelines of WHO and CDC
• DCGI approved 0.5 ml dose in children 6 – 35
months
• Based on the data shared, a 0.5 ml dose of
influenza vaccine can be considered in
children 6 – 35 months age

40. Indian Scenario

41. Mein kahan hun? NH or SH ?

42. Sansanikhez khabar-
W.H.O. Zonewise vaccine recommendations
SH for India (Tropical asia)
NH for Pakistan (Northern africa and middle east) &
NH for Sri Lanka ( Equatorial asia)

43. W.H.O. Influenza NORTHERN HEMISPHERE/ SOUTHERN HEMISPHERE
Not the same as Geographical North & South Hemispheres

44. Seasonality of Influenza and Timing of vaccine in India
Yellow flags show peaks of Influenza activity
Chadha et al,PLOS ONE | DOI:10.1371/journal.pone.0124122 May 4, 2015

45. Koul PA, Broor S, Saha S, et al. Differences in influenza seasonality by
latitude, northern India. Emerg Infect Dis. 2014;20(10):1723-1726.
doi:10.3201/eid2010.140431
• Suggest that policy makers in India review
circulation patterns closely before implementing
influenza intervention plans.
• Their study suggest that cities in India located
north of 30°N latitude can continue vaccination in
the winter.( Most of the Punjab regions and
Chandigarh , Himachal and parts of Haryana are
located North of 30°N latitude )
• But those south of 30°N, including New Delhi,
should consider vaccination in April–May
( at least 2 – 4 weeks before the start of
monsoon peak )

46. El Guerche-Séblain C, Caini S, Paget J, Vanhems P, Schellevis F. Epidemiology and
timing of seasonal influenza epidemics in the Asia-Pacific region, 2010-2017:
implications for influenza vaccination programs. BMC Public Health. 2019

47. In a child previously “primed by 2 doses” , in India, do we need to give
additional NH vaccine in winters if
the child has already received a SH dose in pre April- May ?
• Though the antibody titres wane after 6
months of vaccine , CDC and WHO do not
recommend additional dose in the same year.
• Whether , cold regions in the North of 30 Deg
latitude should choose to give the new NH
strain in winter, is debatable.
• Previously naïve ( unprimed) children may be
given the latest strain of Flu vaccine available
at the time of visit.

48. ACVIP 2020 48
D I F F E R E N C E S I N S T R A I N C O M P O S I T I O N S
SH 2020:
 an A/Brisbane/02/2018 (H1N1)
pdm09-like virus
 an A/South Australia/34/2019
(H3N2)-like virus
 a B/Washington/02/2019-like
(B/Victoria lineage) virus
 a B/Phuket/3073/2013-like virus
(B/Yamagata/16/88 lineage)
NH 2020-21:
 an A/Guangdong-Maonan/
SWL1536/2019 (H1N1) pdm09-like virus
 an A/Hong Kong/2671/2019 (H3N2)-like
virus
 a B/Washington/02/2019 (B/Victoria
lineage)-like virus
 a B/Phuket/3073/2013 (B/Yamagata
lineage)-like virus
Source: 1) WHO Recommended composition of influenza virus vaccines for use in the 2020 southern hemisphere influenza season. Available from:
https://www.who.int/influenza/vaccines/virus/recommendations/2020_south/en/ ; accessed on 11th August 2020 @ 11:30 AM. 2) WHO
Recommended composition of influenza virus vaccines for use in the 2020 - 2021 northern hemisphere influenza season. Available from:
https://www.who.int/influenza/vaccines/virus/recommendations/2020-21_north/en/ ; ; accessed on 11th August 2020 @ 11:30 AM.

49. Why 2 doses below 8 yrs?
Neuzil et alThe Journal of Infectious Diseases, Volume 194, Issue 8, 15 October 2006,
Pages 1032–1039, https://doi.org/10.1086/507309

50. What if 2nd dose is missed in an “unprimed” child less than 9
yrs, and the child comes in the next season for re vaccination,
will you recommend 2 doses or 1 dose?
• Influenza Vaccine Immunogenicity in 6- to 23-Month-
Old Children: Are Identical Antigens Necessary for
Priming?
CONCLUSIONS
Our data suggest that identical influenza antigens are
not necessary for priming vaccine-naive children and
that innovative uses of influenza vaccine, such as as
springtime dose of vaccine, could assist in earlier and
more complete immunization of young children.
Emmanuel B. Walter, Kathleen M. Neuzil, Yuwei Zhu, Mary P. Fairchok, Martha E. Gagliano, Arnold S. Monto
and Janet A. Englund
Pediatrics September 2006, 118 (3) e570-e578; DOI: https://doi.org/10.1542/peds.2006-0198

51. CDC guidelines for children less than 9yrs who have
received only 1 dose previously. Should we give 2
doses or just 1 dose to these children?
https://www.cdc.gov/flu/season/faq-flu-season-
2019-2020.htm
- Children in this age group who have not
previously received two or more total doses of
any trivalent or quadrivalent flu vaccine
(including the nasal spray vaccine) before July 1,
2019, or whose vaccination history is not known,
need two doses of 2019-2020 flu vaccine
administered at least 4 weeks apart.

52. Anti vaccine lobbies question the
“ just 50 %effectiveness of the vaccine”

53. Even a vaccine with little efficacy can do wonders
If Coverage is more

54. Hard fought gains against VPD’s at risk- warns WHO
Disruption of immunization , even for
brief periods, can raise the likelihood of
outbreak prone VPD
Such VPD’S may increase mortality and
morbidity in young infants and
vulnerable age groups, and put greater
burden on health systems already
overwhelmed by COVID 19
WHO urges countries to prioritize the
continuation of routine immunization
practices of children in essential delivery
, as well as adult vaccinations such as
influenza for groups most at risk

55. IAP- ACVIP guidelines during SARS- CoV 2 pandemic 2020
• Vaccinate newborns in maternity set ups before discharge
• BCG , OPV and HEP B to be given
• Prioritize primary vaccination series. Avoid postponing these vaccines.
• DTP, HIB, HEP – B, IPV/OPV,ROTAVIRUS,PCV, MR/ MMR, VARICELLA, INFLUENZA
• Prioritize Pneumococcal and Influenza vaccination to vulnerable group.
• Health personnel should be up to date in their age specific vaccination.
• Typhoid conjugate vaccines may be clubbed with Influenza vaccine at 6 months
or with MMR/MR at 9 months
• JE vaccines wherever applicable should be administered at 1 yr
• Hepatitis A and HPV vaccines may be postponed to a later date. They may be
administered after the priority vaccines have been given
• Multiple vaccines can be given in the same sitting without fearing any increased
adverse effects
• Boosters may be postponed to a later date , if logistic issues of transport etc
exist.
• If the child is in a healthcare facility , this opportunity should be utilised to
administering any eligible vaccine