Influenza Virus Infection Induces a Narrow Antibody Response in Children but a Broad Recall Response in Adults

In contrast to influenza virus vaccination, natural infection induces long-lived and relatively broad immune responses. However, many aspects of the antibody response to natural infection are not well understood. Here, we assessed the immune response after H1N1 influenza virus infection in children and adults in a Nicaraguan household transmission study using an influenza virus protein microarray (IVPM). This technology allows us to simultaneously measure IgG and IgA antibody responses to hemagglutinins of many different virus strains and subtypes quantitatively with a high throughput. We found that children under 6 years of age responded to natural infection with a relatively narrow response that targeted mostly the hemagglutinin of the strain that caused the infection. Adults, however, have a much broader response, including a boost in antibodies to many group 1 subtype hemagglutinins. Also, a strong recall response against historic H1 hemagglutinins that share the K133 epitope with the pandemic H1N1 virus was observed. Of note, some children, while responding narrowly within H1 and group 1 hemagglutinins, induced a boost to H3 and other group 2 hemagglutinins when infected with H1N1 when they had experienced an H3N2 infection earlier in life. This is an interesting phenomenon providing evidence for immune imprinting and a significant new insight which might be leveraged in future universal influenza virus vaccine strategies. Finally, preexisting immunity to pandemic H1 hemagglutinins was significantly associated with protection from infection in both children and adults. In adults, preexisting immunity to non-H1 group 1 hemagglutinins was also significantly associated with protection from infection.