Revisiting live attenuated influenza vaccine efficacy among children in developing countries

Seasonal influenza epidemics cause significant pediatric mortality and morbidity worldwide. Live attenuated influenza vaccines (LAIVs) can be administered intranasally, induce a broad and robust immune response, demonstrate higher yields during manufacturing as compared to inactivated influenza vaccines (IIVs), and thereby represent an attractive possibility for young children in developing countries. We summarize recent pediatric studies evaluating LAIV efficacy in developing countries where a large proportion of the influenza-virus-associated respiratory disease burden occurs. Recently, two randomized controlled trials (RCTs) assessing Russian-backbone trivalent LAIV in children reported contradictory results; vaccine efficacy varied between Bangladesh (41 %) and Senegal (0.0 %) against all influenza viral strains. Prior to 2013, Ann Arbor-based LAIV demonstrated superior efficacy as compared to IIV. However, due to low effectiveness of the Ann Arbor-based LAIV against influenza A(H1N1)pdm09-like viruses, the CDC Advisory Committee on Immunization Practices (ACIP) recommended against the use of LAIV during the 2016-17 and 2017-18 influenza seasons. Reduced replicative fitness of the A(H1N1)pdm09 LAIV strains is thought to have led to the low effectiveness of the Ann-Arbor-based LAIV. Once the A(H1N1)pdm09 component was updated, the ACIP reintroduced the Ann-Arbor-based LAIV as a vaccine choice for the 2018-19 influenza season. In 2021, results from a 2-year RCT evaluating the Russian-backbone trivalent LAIV in rural north India reported that LAIV demonstrated significantly lower efficacy compared to IIV, but in Year 2, the vaccine efficacy for LAIV and IIV was comparable. A profounder understanding of the mechanisms underlying varied efficacy of LAIV in developing countries is warranted. Assessing replicative fitness, in addition to antigenicity, when selecting annual A(H1N1)pdm09 components in the Russian-backbone trivalent LAIVs is essential and may ultimately, enable widespread utility in resource-poor settings.