Secretory and systemic immunological response in children infected with live attenuated influenza A virus vaccines

An enzyme-linked immunosorbent assay was used to measure isotype-specific antibody to purified hemagglutinin (HA) of influenza A virus, using serum and nasal-wash specimens from young children undergoing primary infection with live cold-adapted influenza A/Alaska/77 (H3N2) or A/Hong Kong/77 (H1N1) candidate vaccine virus. The serum antibody response followed the pattern expected for a primary viral infection. Each of 17 vaccinated children had a serum immunoglobulin G (IgG) HA antibody response, 16 had an IgM antibody response, and 13 had an IgA antibody response. Nasal-wash HA antibody was detected in the IgA, IgM, and IgG isotypes. Of the 17 vaccinated children, 14 had an IgA response, 13 had an IgM response, and 9 had an IgG response. Most of the IgA and IgM HA antibody was actively secreted locally, whereas only some of the IgG HA antibody could be shown to be actively secreted into the respiratory tract. There was a good correlation between the level of nasal-wash antibodies measured by the HA-specific IgA enzyme-linked immunosorbent assay and by a plaque neutralization assay. These data indicate that intranasal vaccination of susceptible children with live, attenuated, cold-adapted influenza A viruses efficiently stimulates both systemic and local antibody responses.