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 , 201415 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 201415 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 635 months 0.25 mL 2 doses 1 month apart Single annual dose as soon as new vaccine is released 38 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. 20092011. Mumbai, 2011, pp. 51144.

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 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