The document discusses the use of Live Attenuated Influenza Vaccine (LAIV) in India, highlighting its effectiveness, safety, and recommendations for immunization in children and high-risk populations. It compares LAIV with traditional influenza vaccines (TIV), noting that LAIV is more effective in inducing immune responses and is easier to administer. Key recommendations include prioritizing vaccination for high-risk groups and the ideal timing for vaccination in relation to seasonal influenza peaks.

1. LAIV – Should we use it in India?
Dr Gaurav Gupta
Charak Clinics, Chandigarh
docgaurav@gmail.com

2. Conflict of Interest
 Received grants from various vaccine
manufacturers including
 - Sanofi Pasteur
 - GSK
 - Novartis
 - SII
(Manufacturers of different Influenza vaccines)

3. Overview
 Should we use the Flu vaccine at all?
 Latest recommendations from CDC / NHS
 When to use LAIVs (Indications US v/s UK)
 When NOT to use LAIVs (Contraindications/
precautions – MMWR)
 How does LAIV differ from TIV
 Talking about Nasovac & Nasovac S
 FAQs

4. Should we use the Flu vaccine at all?

5. IAP recommendation
5 to 10% of ARI cases-caused
by Influenza in India
Ref: Indian Pediatr. 2013 Sep;50(9):867-74.

6. http://www.who.int/influenza/vaccines/use/en/

7. SAGE Data- Protection against
influenza
 Vaccine effectiveness studies have found VE of 60-85%
in children < 5 yrs age when vaccine strains match well
with circulating strains
 Limited data indicate additional protection of
unvaccinated household and community contacts by
immunization of children
Sage working group: Background Paper on Influenza Vaccines and Immunization. April 2012

8. Clinical Effectiveness of Influenza
vaccine-1
Fully vaccinated cohort (n=106) vs. Unvaccinated cohort (n=282)
Parameters Fully
Vaccinate
d cohort
(%)
Unvaccinat
ed cohort
(%)
Relative
Risk
VE % P-value
Influenza like illness 0.9 35.5 0.0357
97 % 0.0009
Visits to Physician 2.8 38.7 0.0987 90 % 0.0001
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.

9. Influenza Activity And Peaks

10. Ideal time of Influenza Vaccination in
India: Summary
• Best time to vaccinate against influenza in India is at least 1
month before the monsoons with the latest available vaccine
having updated strains.1
• However, any child that comes to the doctor later in the year,
post the monsoons with no history of influenza vaccination in the
past 1 year, should not be made to wait till next year and should
be vaccinated with the latest strains available so as to protect
from the winter peak.
• These children who have been vaccinated late (NH) in the year
should be shifted to early (SH)vaccination next year and same
cycle (SH) should be continued every year.
1. Vashistha VM et al. Influenza Vaccination in India: Position Paper of IAP, 2013. Indian Pediatrics 2013:50;867-74

11. What are the recommendations

12. Vaccine Recommendations
• Ideally, all
individuals
should have the
opportunity to be
vaccinated
against
influenza.
• Priority should
be given to high
risk population
• All those
aged over 6
months in a
clinical at-risk
group
• Only in all
high risk
children >6
months
• Universal
Vaccination
of all children
from the age
of 6 months.
• Special
attention for
children upto
60 months
• Routine influenza
vaccination is
recommended
for all persons
aged ≥6 months
*CEVAG: Central European Advisory Group
http://www.who.int/docstore/wer/pdf/2002/wer7728.pdf
http://www.cdc.gov/mmwr/preview/mmwrhtml/rr59e0729a1.htm?s_cid=rr59e0729a1_e
http://www.sehd.scot.nhs.uk/cmo/CMO(2010)14.pdf
http://www.biomedcentral.com/content/pdf/1471-2334-10-168.pdf
*

13. Prioritization of target groups as per IAP
1. Elderly individuals (>65 years) and nursing-home residents
(the elderly or disabled)
2. Individuals with chronic medical conditions including
individuals with HIV/AIDS, and pregnant women (especially
to protect infants 0-6 months)
3. Other groups: health care workers including professionals,
individuals with asthma, and children from ages 6 months to
2 years.
4. Children aged 2-5 years and 6-18 years, and healthy young
adults.
Amongst pediatric population, apart from the children with
chronic medical conditions (see above), the children below 2
years * IAP of position age should paper of be Influenza considered – Indian a Pediatrics, target group September for influenza
2013
immunization because of a high burden of severe disease in
this group. *

14. Center for Disease Control and prevention.
Recommendations , 2014–15
1. Routine annual influenza vaccination is
recommended for all persons aged ≥6 months who
do not have contraindications
2. Live attenuated influenza vaccine (LAIV) should be
preferred for healthy children aged 2 through 8
years, for the 2014–15 season
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6332a3.htm

15. NHS recommendations – 2014-
15
 An annual nasal flu vaccine for children is
available on the NHS for all two, three and four
year olds.
 Over time, potentially all children between the
ages of two and 16 could be vaccinated each
year against flu using the nasal spray.
 Children aged two to 17 who are at extra risk
from flu because they have a long-term health
condition, such as diabetes, heart or lung
disease, will have the annual flu nasal spray
instead of the annual flu jab
 Children with mild or moderate asthma are able to
have the flu nasal spray

16. What are the types of Influenza
vaccines available?

17. Types of Influenza vaccines
Egg Based
 Nomenclature changed from TIV to IIV (Inactivated
Influenza Vaccine) IIV3 was only available in India
previously.
 LAIV 3/4
 Quadrivalent Influenza Vaccine – IIV4
 Adjuvanted IIV3
Non egg based
 Cell culture based ccIIV 3
 Recombinant RIV3

18. TIV Influenza Vaccination
Schedule
Age
Vaccine
Dose
Initial
Vaccination
Subsequent
Vaccination
635 months 0.25 mL
2 doses
1 month apart
Single annual
dose as soon as
new vaccine is
released
38 years 0.5 mL
2 doses
1 month apart
≥9 years 0.5 mL 1 Dose
Individual vaccines. In: Yewale V, Choudhury P, Thacker N (eds). IAP Guide Book on Immunization. IAP Committee on Immunization.
20092011. Mumbai, 2011, pp. 51144.

19. LAIV (Nasovac S) Schedule
 A single intranasal dose recommended for people
above the age of 2 years.
 This vaccination is similar to what is being
advised by NHS for routine immunization of
healthy kids as well.

20. Advantages of LAIV

21. LAIV
 Mimic natural infection and therefore it is expected
that LAIV induce a more rapid and broader
immune response
 LAIV induce IgA in natural tract which neutralize
the virus at portal entry
 Administered intranasal making it painless
 Used successfully in Russian federation-
“Microgen”
 Used successfully “Medimmune”
 Vaccines is revised twice annually for prevalent
strain of virus

22. Advantages of LAIV
Serum
antibodies
Adv.
Nasal
Specific
intranasal
IgA
Cell
mediated
immune
Protection response
against
drifted
virus
Herd
immunity
Painless
Mimic
natural
route of inf
Ref: MMWR Morb Mortal Wkly Rep. 2014 Aug 15;63(32):691-7.

23. LAIV
Precautions & Contraindications

24. CDC – Contraindications
Contraindications for LAIV
1. Persons aged <2 years or >49 years;
2. Children aged 2 through 17 years who are
receiving aspirin or aspirin-containing products;
3. Severe allergic reaction to flu vaccine previously
4. Pregnant women *
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6332a3.htm

25. CDC - Contraindications
4. Severely Immunosuppressed persons
5. Persons with a history of egg allergy *
6. Children aged 2 through 4 years who have asthma
or who have had a wheezing episode noted in the
medical record within the past 12 months
7. Persons who have taken influenza antiviral
medications within the previous 48 hours
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6332a3.htm

26. Precautions for LAIV - CDC
 Asthmatics might be at increased risk for
wheezing after administration of LAIV
 Theoretically, Persons with other underlying
medical conditions that might predispose them to
complications after wild-type influenza infection
(e.g., chronic pulmonary, cardiovascular [except
isolated hypertension], renal, hepatic, neurologic,
hematologic, or metabolic disorders [including
diabetes mellitus] ) *
These conditions, in addition to asthma in persons
aged ≥5 years, should be considered precautions
for the use of LAIV.

27. LAIV Vs TIV

28. Head to Head comparison of LAIV &
IIV
LAIV IIV
Grows in nasopharaynx Not grow
Nasal spray Injection
Grows in cooler areas of nasal tract but
stop growing in LRTI
Not grow
Mimic natural infection and induce
double layer immunity
Serves only as a dose of antigen to the
immune system
Induce local, systemic and cell mediated
immunity
May not induce local immunity, good
systemic response
Provide local immunity No local immunity
More effective Effectiveness less than LAIV
Painless Painful
Negligible side effect Reported side effects
Cost effective Comparatively expensive
Provide herd immunity Not possible
Preferred in children Children afraid of needles

29. LAIV Vs TIV in children
 In over 26,000 children aged 6 months to 17 years,
LAIV demonstrated 44 – 48 % fewer cases of
culture positive influenza illness caused by similar
strains and all strains, respectively as compared to
TIV!
 Overall efficacy of LAIV was 83 % in first year & 87
% in second year.
Ref: Vaccine. 2012 Jan 20;30(5):886-92. doi: 10.1016/j.vaccine.2011.11.104. Epub
2011 Dec 7.

30. Live attenuated versus inactivated
influenza vaccine in infants and young
children
 54.9% fewer cases of cultured-confirmed
influenza in the group that received live attenuated
vaccine than in the group that received inactivated
vaccine (153 vs. 338 cases, P<0.001)
 Highly effective, safe vaccine for children 12 to 59
months of age who do not have a history of asthma
or wheezing
Ref: N Engl J Med. 2007 Feb 15;356(7):685-96.

31. LAIV Vs TIV in children
LAIV vaccinated children shows 46% fewer cases
of influenza illness caused by antigenically similar
strains
Similarly, for studies including older children who had
been previously vaccinated, those receiving one LAIV
dose experienced 35% fewer cases of influenza illness
than those receiving one TIV dose
Ref: Vaccine. 2009;27(7):1101-10.

32. Cost benefit of LAIV
The estimated offsets in direct and indirect costs
saved USD15.80 and USD37.72 per vaccinated
child, respectively. LAIV had a net total cost
savings of USD45.80 per child relative to TIV
Ref: Vaccine. 2003 May 16;21(17-18):2207-17.

33. Nasovac & Nasovac S

34. SII H1N1 vaccine (Nasovac)
 Found safe in preclinical studies
 Phase I conducted in 50 healthy adults aged 18-49
years
 Phase II/III conducted in 280 healthy persons:
adults, elderly & children and adolescents
 Found safe and immunogenic
 Based on this, the vaccine was licensed by DCGI
on 18 June 2010

35. Post marketing experience - Nasovac
 Around 3 million doses were used in India during
the pandemic
 Total 7 PSURs submitted to DCGI
 A PMS in 2000 vaccinees – safety proven
 Another PMS in 7565 vaccinees – safety
confirmed
 Case control study showed excellent effectiveness
 The data established the safety and efficacy of the
live attenuated platform
 Prequalified by WHO on 26 Nov 2012

36. Safety and effectiveness of LAIV in
India
LAIV effectiveness – 76%
Ref: Hum Vaccin Immunother. 2014 March

37. Safety and effectiveness of LAIV in
India
Solicited reaction- 0.65%
cases
No H1N1 case upto one year
Ref: Hum Vaccin Immunother. 2013 Jan;9(1):122-4. doi: 10.4161/hv.22317.

38. Safety and effectiveness of LAIV in
India
LAIV safety – No serious ADR
Ref: Vaccine
after 2.5 million doses

39. Nasovac S
 Freeze dried, live attenuated trivalent vaccine for
administration by intranasal spray.
 The influenza virus strain is
 (a) cold-adapted (ca) (i.e., it replicates efficiently at
25ºC, a temperature that is restrictive for replication
of many wild-type influenza viruses);
 (b) temperature-sensitive (ts) (i.e., it is restricted in
replication at 39ºC, a temperature at which many
wild-type influenza viruses grow efficiently); and
 (c) attenuated (att) (it does not produce classic
influenza-like illness in the ferret model of human
influenza infection).

40. SII Influenza vaccine (Nasovac-S)
 Live, attenuated, trivalent seasonal influenza
vaccine for administration by intranasal spray
 Supplied along with sterile water for inhalation as a
diluent, syringe, needle, intranasal spray device
and dose divider
 Each vial of the vaccine contains following strains:

41. Ferret Data p(H1N1)
•Severely affected,
•Dark hyperaemic &
consolidated lung
•No evident discernable lesions.
Normal aerated lung tissue is
bright pink in color

42. SII Influenza vaccine (Nasovac-S)
 Ferret Studies
1. Little or no (<5%) affected lung parenchyma
2. Decreased or absent viral load after challenge in
vaccinated animals as compared to control
animals
 Clinical Studies
1. Phase I study - conducted in 50 healthy adults
2. Phase II/III study - conducted in healthy adults,
elderly & children and adolescents (280)
3. Was found safe and immunogenic
4. Licensed by DCGI

43. Challenges
 Limited human data for Nasovac S
 Extrapolation of data from other vaccines /
countries ??
 No data available for use in high risk population
 Confusing recommendations for LAIV use
internationally.

44. Conclusion
1. LAIVs are highly safe and effective vaccines.
2. There is a long history of their use in USA and
Russia and in UK as well.
3. Nasovac-S is easy to administer, making
operationally an attractive option
4. A single intranasal dose is recommended for
adults, and children >=2 years.

45. FAQs

46.  When a child has been given a dose of
injectable influenza vaccine, can I give second
dose as nasal spray?
 Yes. As long as a child is eligible to receive nasal
spray vaccine (i.e., is in the proper age range and
health status), it is acceptable to give 1 dose of
each type of influenza vaccine. The doses should
be spaced at least 4 weeks apart.

47.  A five-year-old child received her second
MMR a week ago. How long should she wait
before receiving live attenuated influenza
vaccine (LAIV)?
 LAIV can be administered simultaneously with
another live vaccine (for example, MMR,
varicella), but if not given at the same time, ACIP
recommends waiting four weeks before
administering the second live vaccine.

48.  Can LAIV be administered to persons with
minor acute illnesses, such as a mild upper
respiratory infection (URI) with or without
fever?
 Yes, however, if clinical judgment suggests nasal
congestion is present that might impede delivery
of the vaccine to the nasopharyngeal mucosa,
deferral of administration should be considered
until the congestion resolves.

49. Thank you