TY - JOUR
T1 - Efficacy of live attenuated and inactivated influenza vaccines among children in rural India: a 2-year, randomized, triple-blind, placebo-controlled trial
AU - Krishnan, Anand
AU - Dar, Lalit
AU - Saha, Siddhartha
AU - Narayan, Venkatesh Vinayak
AU - Kumar, Rakesh
AU - Kumar, Ramesh
AU - Amarchand, Ritvik
AU - Dhakad, Shivram
AU - Chokker, Reshmi
AU - Choudekar, Avinash
AU - Gopal, Giridara
AU - Choudhary, Aashish
AU - Potdar, Varsha
AU - Chadha, Mandeep
AU - Lafond, Kathryn E
AU - Lindstrom, Stephen
AU - Widdowson, Marc-Alain
AU - Jain, Seema
N1 - FTX; DOAJ; (CC0 1.0); No ITM affiliation
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
U2 - 10.1371/journal.pmed.1003609
DO - 10.1371/journal.pmed.1003609
M3 - A1: Web of Science-article
C2 - 33914729
SN - 1549-1676
VL - 18
JO - PLoS Medicine
JF - PLoS Medicine
IS - 4
M1 - e1003609
ER -