Summary This pediatric live attenuated influenza vaccine (LAIV) study is the first to show long-term, cross-reactive CD8 + T-cell responses to LAIVs. In the absence of preexisting antibodies, LAIV boosted preexisting T-cell responses to genetically diverse, wild-type IAVs to which the children were not previously exposed. Abstract Background. Live attenuated influenza vaccines (LAIVs) stimulate a multifaceted immune response including cellular immunity, which may provide protection against newly emerging strains. This study shows proof of concept that LAIVs boost preexisting, cross-reactive T cells in children to genetically diverse influenza A virus (IAV) 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 (FluoroSpot) with heterologous H1N1 and H3N2 IAVs and CD8 + peptides from the internal proteins (matrix protein 1 [M1], nucleoprotein [NP], polymerase basic protein 1 [PB1]). Serum antibody responses were determined by means of hemagglutination inhibition assay. Blood samples were collected before vaccination and up to 1 year after vaccination. Results. Preexisting cross-reactive T cells to genetically diverse IAV strains were found in the majority of the children, which were further boosted in 50% of them after receipt of LAIV. Further analyses of these T cells showed significant increases in CD8 + T cells, mainly dominated by NP-specific responses. After vaccination with 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 toward the desired universal influenza vaccine.
【저자키워드】 Vaccine, Cellular immune response, Influenza, protection, children, T-cell, Heterologous, cross-reactive, LAIV,