Phase I/II randomized double-blind study of the safety and immunogenicity of a nonadjuvanted vero cell culture-derived whole-virus H9N2 influenza vaccine in healthy adults

Abstract

Studies on candidate pandemic vaccines against avian influenza viruses have focused on H5N1, but viruses of other subtypes, such as A/H9N2, are also considered to have pandemic potential. We investigated the safety and immunogenicity of two immunizations with one of five different antigen doses (ranging from 3.75 to 45 μg of hemagglutinin antigen) of a nonadjuvanted whole-virus G9 lineage H9N2 influenza virus vaccine in healthy adults aged 18 to 49 years. The antibody responses were measured by hemagglutination inhibition (HI), microneutralization (MN), and single radial hemolysis (SRH) assays. To investigate a hypothesis that previous exposure to H2N2 viruses in subjects born in or before 1968 might prime for more robust antibody responses to H9N2 vaccination than that in subjects born after 1968, a post hoc age-stratified analysis of antibody responses was done. Both vaccinations in all dose groups were safe and well tolerated. No vaccine-related serious adverse events were reported, and the majority of the adverse reactions were rated as mild. The rates of injection site reactions were lower in the 3.75-μg- and 7.5-μg-dose groups than those in the higher-dose groups; the rates of systemic reactions were similar across all dose groups. The seroprotection rates among the different dose groups 21 days after the second immunization ranged from 52.8% to 88.9% as measured by HI assay, from 88.7% to 98.1% or 82.7% to 96.2% as measured by MN assay (MN titer cutoffs, 1:40 and 1:80, respectively), and from 94.2% to 100% as measured by SRH assay. Higher antibody responses were not induced in subjects born in or before 1968. These data indicate that a nonadjuvanted whole-virus H9N2 vaccine is well tolerated and immunogenic in healthy adults. (This study has been registered at ClinicalTrials.gov under registration no. NCT01320696.).

FIG 1

Flow chart of the study participants through the trial.

FIG 2

Effect of age group on antibody responses to H9N2 vaccine. Antibody responses at baseline, 21 days after the first and second vaccinations, and 180 days after the first vaccination, as determined by an HI assay (A), MN assay (B), and SRH assay (C) in participants born in or before 1968 (black bars) and after 1968 (gray bars). The data are the geometric mean titers (GMTs) or geometric mean SRH area, and 95% CIs, pooled for all dose groups.