Comparisons of the Humoral and Cellular Immune Responses Induced by Live Attenuated Influenza Vaccine (LAIV) and Inactivated Influenza Vaccine (IIV) in Adults.

Both live attenuated influenza vaccine (LAIV) and inactivated influenza vaccines (IIV) induce protective immunity against influenza. There is evidence that LAIV induces superior protection in children, whereas IIV may induce superior protection in adults. The immune mechanisms responsible for these differences have not been identified. We previously compared LAIV and IIV in young children 6-36 months of age, and demonstrated that while both induced similar hemagglutination-inhibiting (HAI) antibody responses, only LAIV induced significant increases in T cell responses. Here, 37 healthy adult subjects 18-49 years of age were randomized to receive seasonal influenza vaccination with LAIV or IIV. Influenza-specific HAI, T cell and secretory IgA (sIgA) responses were studied pre- and post-vaccination. In contrast to responses seen in young children, LAIV induced only minimal increases in serum HAI responses in adults, significantly lower than responses induced by IIV. Both LAIV and IIV similarly induced only transient T cell responses in adults reactive with whole replication competent virus. In contrast, influenza-specific sIgA responses were more strongly induced by LAIV compared to IIV vaccine. Our previous studies suggest that LAIV vaccine may be more protective than IIV in young children not previously exposed to influenza or influenza vaccines due to increased vaccine-induced T cell and/or secretory IgA responses. Our current work suggests that in adults with extensive and partially cross-reactive pre-existing influenza immunity, LAIV boosting of sIgA responses reactive with hemagglutinin (HA) and non-HA antigenic targets expressed by circulating influenza strains may be an important additional mechanism of vaccine-induced immunity.