Immunity to influenza A virus infection in young children: a comparison of natural infection, live cold-adapted vaccine, and inactivated

Live attenuated, cold-adapted (ca) influenza A vaccines administered intranasally have been well characterized as safe and immunogenic, but comparative data on protective efficacy are required for further development. In this study, 59 young children weredivided into the following four groups based on prior exposure to influenza A (H3N2) virus: nat-ural infection, live ca vaccine given intranasally, inactivated vaccine given im, and no previous exposure. Virus challenge with homologous liveca vaccine occurred 12months after vaccination or natural infection. Prior natural infection and live ca vaccine signifi-cantly reduced ca virus shedding after challenge compared with inactivated vaccine or no prior exposure to influenza A virus. Prechallenge nasal IgA, detected almost exclu-sively in subjects naturally infected or vaccinated with live ca virus, was associated with protection. Although inactivated vaccine failed to produce significant local IgA during the primary response, it seemed to prime for secondary local antibody responses after challenge with live ca virus. Influenza A virus infections remain a major public health concern [1-4], and research efforts continue to focus on disease prevention by vaccination. Cur-rently available inactivated vaccines given im are 60010-90010 effective in the short term when closely matched antigenically with epidemic strains [5]. There are disadvantages, however, to this vaccina-tion approach. Young children require two injections of the current split-virus (subvirion) vaccine to in-duce protective levels of serum antibody [6, 7]. Fur-thermore, the cumulative efficacy of these vaccines, Received for publication 1 July 1985, and in revised form 2