Phase I, randomized, controlled trial to study the reactogenicity and immunogenicity of a nasal, inactivated trivalent influenza virus vaccine in healthy adults.

We performed a randomized, placebo-controlled, dose-escalating clinical trial to evaluate the safety and immunogenicity of an inactivated, split virion, trivalent, nasal influenza vaccine using lipid/polysaccharide molecules as carriers. A total of 64 adults (mean age 29; range 19-69 years) were randomly allocated to receive a mixture of lipid/polysaccharide carrier molecules and 7.5, 15, or 30 microg hemagglutinin antigen of each of the three influenza strains (A/Johannesburg/82/96 [H1N1], A/Nanchang/933/95 [H3N2], B/Harbin/07/94) or placebo via nasal spray on two occasions separated by 28 days. Adverse events were assessed immediately after immunization and for 14 days after each dose. Nasal and serum antibodies were measured before and two weeks after each dose. All but three participants completed the study; no withdrawals were because of adverse events. Adverse events were similar immediately after immunization except for anterior nasal dripping after the first dose which was more common in the combined vaccine groups (64.4%) than in the placebo group (31.3%; p < 0.05). A similar trend was observed after the second dose. Nasal dripping was also more common in the first two days after immunization in the vaccine groups than the placebo group (31.3%-50% vs. 0%) with no difference with increasing vaccine dose. The vaccine elicited a modest serum antibody response against all three viruses, with the highest dose eliciting the highest serum antibody levels. In contrast, significant nasal antibody rises were observed for all three viruses; again, the 30 microg group achieved the highest mucosal antibody levels at the earliest time points. We conclude that this trivalent, split virion, inactivated nasal influenza vaccine formulated with lipid/polysaccharide molecule carriers is well tolerated and modestly immunogenic in healthy adults.