An open-label phase I trial of a live attenuated H2N2 influenza virus vaccine in healthy adults

Background Live attenuated influenza vaccines (LAIV) against a variety of strains of pandemic potential are being developed and tested. We describe the results of an open-label phase I trial of a live attenuated H2N2 virus vaccine. Objectives To evaluate the safety, infectivity, and immunogenicity of a live attenuated H2N2 influenza virus vaccine. Participants/methods The A/Ann Arbor/6/60 (H2N2) virus used in this study is the attenuated, cold-adapted, temperature-sensitive strain that provides the genetic backbone of seasonal LAIV (MedImmune). We evaluated the safety, infectivity, and immunogenicity of two doses of 10⁷ TCID₅₀ of this vaccine administered by nasal spray 4weeks apart to normal healthy seronegative adults. Results Twenty-one participants received a first dose of the vaccine; 18 participants received a second dose. No serious adverse events occurred during the trial. The most common adverse events after vaccination were headache and musculoskeletal pain. The vaccine was restricted in replication: 24% and 17% had virus detectable by culture or rRT-PCR after the first and second dose, respectively. Antibody responses to the vaccine were also restricted: 24% of participants developed an antibody response as measured by either hemagglutination-inhibition assay (10%), or ELISA for H2 HA-specific serum IgG (24%) or IgA (16%) after either one or two doses. None of the participants had a neutralizing antibody response. Vaccine-specific IgG-secreting cells as measured by enzyme-linked immunospot increased from a mean of 0·5 to 2·0/10⁶ peripheral blood mononuclear cells (PBMCs); vaccine-specific IgA-secreting cells increased from 0·1 to 0·5/10⁶ PBMCs. Conclusions The live attenuated H2N2 1960 AA ca vaccine demonstrated a safety profile consistent with seasonal trivalent LAIV but was restricted in replication and minimally immunogenic in healthy seronegative adults. Published 2012. This article is a US Government work and is in the public domain in the USA.