Background:

Live attenuated influenza vaccines (LAIV) stimulate a multifaceted immune response including cellular immunity, which may provide protection against newly emerging strains. This study shows proof of concept that LAIV boosts pre-existing, cross-reactive T-cells in children to genetically diverse influenza A strains to which the children had not been exposed.

Methods:

We studied the long-term cross-reactive T-cell response in 14 trivalent LAIV vaccinated children using the fluorescent immunospot assay (FluroSpot) with heterologous H1N1 and H3N2 influenza A viruses and CD8 peptides from the internal proteins (M1, NP, PB1). Serum antibody responses were determined by the Hemagglutination Inhibition (HI). Blood samples were collected before vaccination and up to one year post-vaccination.

Results:

Pre-existing cross-reactive T-cells to genetically diverse influenza A strains were found in the majority of the children, which were further boosted in 50% of the children after LAIV. Further analyses of these T-cells showed significant increases in CD8+ T-cells, mainly dominated by NP specific responses. After LAIV, the youngest children showed the highest increase in T-cell responses.

Conclusion:

LAIV boosts durable, cross-reactive T-cell responses in children and may have a clinically protective effect at the population level. LAIV may be a first step towards the desired universal influenza vaccine.