Background: Intranasal trivalent, cold-adapted, live attenuated influenza vaccine (CAIV-T) is a promising alternative to inactivated vaccine for protection against influenza in children. A multicenter, double-blind, placebo controlled trial of CAIV-T (Aviron, Mountain View, CA) has demonstrated efficacy against influenza A/H3N2 (95%) and influenza B (91%) [Belshe R, et al. IDSA 1997, abst. 762]. However, correlates of immunity are not well defined. Antigen-specific mucosal immunity is thought to be important for protection against influenza but has been difficult to measure, particularly in young children. Objective: To determine whether CAIV-T induces mucosal influenza-specific IgA (Flu-IgA) to H1N1, H3N2, and B viruses contained in the vaccine. Methods: We collected nasal washes on the first 19 children (ages 15-55 months) enrolled at Vanderbilt as part of the efficacy trial described above. Vaccine or placebo (2:1 ratio) was administered by nasal spray in two doses given two months apart. Flu-IgA to purified influenza hemagglutinins was measured by kinetic ELISA (mOD/min) in nasal washes obtained pre-immunization and one month after dose 2. Each sample was run in two different assays and the mean value calculated. We compensated for assay-to-assay variation by expressing results as a dilution of the same serum standard with high titer Flu-IgA run in each assay and by correcting for the total secretory IgA in each sample. A mucosal Flu-IgA response was defined as a post/pre-vaccination ratio >95%ile of Flu-IgA ratios of 10 daily nasal washes from two unvaccinated adults. Results: The mucosal Flu-IgA assay was reproducible with minimal intratest variation for all three antigens (95%ile for duplicate ratios <1.7). The frequency of mucosal Flu-IgA response to each of the three vaccine antigens is shown in the table. Conclusions: Two doses of CAIV-T induced a mucosal IgA response to all three influenza vaccine antigens in the majority of children. Mucosal influenza-specific IgA merits further investigation as a correlate of protection.

Table 1 No. (%) of Subjects with Mucosal Flu-IgA Response to Two Doses of Vaccine
Full size table