Efficacy of live attenuated and inactivated influenza vaccines among children in rural India: a 2-year, randomized, triple-blind, placebo-controlled trial

Anand Krishnan, Lalit Dar, Siddhartha Saha, Venkatesh Vinayak Narayan, Rakesh Kumar, Ramesh Kumar, Ritvik Amarchand, Shivram Dhakad, Reshmi Chokker, Avinash Choudekar, Giridara Gopal, Aashish Choudhary, Varsha Potdar, Mandeep Chadha, Kathryn E Lafond, Stephen Lindstrom, Marc-Alain Widdowson, Seema Jain

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Abstract

BACKGROUND: Influenza is a cause of febrile acute respiratory infection (FARI) in India; however, few influenza vaccine trials have been conducted in India. We assessed absolute and relative efficacy of live attenuated influenza vaccine (LAIV) and inactivated influenza vaccine (IIV) among children aged 2 to 10 years in rural India through a randomized, triple-blind, placebo-controlled trial conducted over 2 years.

METHODS AND FINDINGS: In June 2015, children were randomly allocated to LAIV, IIV, intranasal placebo, or inactivated polio vaccine (IPV) in a 2:2:1:1 ratio. In June 2016, vaccination was repeated per original allocation. Overall, 3,041 children received LAIV (n = 1,015), IIV (n = 1,010), nasal placebo (n = 507), or IPV (n = 509). Mean age of children was 6.5 years with 20% aged 9 to 10 years. Through weekly home visits, nasal and throat swabs were collected from children with FARI and tested for influenza virus by polymerase chain reaction. The primary outcome was laboratory-confirmed influenza-associated FARI; vaccine efficacy (VE) was calculated using modified intention-to-treat (mITT) analysis by Cox proportional hazards model (PH) for each year. In Year 1, VE was 40.0% (95% confidence interval (CI) 25.2 to 51.9) for LAIV and 59.0% (95% CI 47.8 to 67.9) for IIV compared with controls; relative efficacy of LAIV compared with IIV was -46.2% (95% CI -88.9 to -13.1). In Year 2, VE was 51.9% (95% CI 42.0 to 60.1) for LAIV and 49.9% (95% CI 39.2 to 58.7) for IIV; relative efficacy of LAIV compared with IIV was 4.2% (95% CI -19.9 to 23.5). No serious adverse vaccine-attributable events were reported. Study limitations include differing dosage requirements for children between nasal and injectable vaccines (single dose of LAIV versus 2 doses of IIV) in Year 1 and the fact that immunogenicity studies were not conducted.

CONCLUSIONS: In this study, we found that LAIV and IIV vaccines were safe and moderately efficacious against influenza virus infection among Indian children.

TRIAL REGISTRATION: Clinical Trials Registry of India CTRI/2015/06/005902.

Original languageEnglish
Article numbere1003609
JournalPLoS Medicine
Volume18
Issue number4
Number of pages17
ISSN1549-1676
DOIs
Publication statusPublished - 2021

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