A cell-based H7N1 split influenza virion vaccine confers protection in mouse and ferret challenge models

Abstract

Background: In recent years, several avian influenza subtypes (H5, H7 and H9) have transmitted directly from birds to man, posing a pandemic threat. Objective: We have investigated the immunogenicity and protective efficacy of a cell based candidate pandemic influenza H7 vaccine in pre-clinical animal models. Methods: Mice and ferrets were immunised with two doses of the split virus vaccine (12-24 μg haemagglutinin) with or without aluminium hydroxide adjuvant and challenged 3 weeks after second dose with the highly pathogenic A/chicken/Italy/13474/99 (H7N1) virus. The H7N1-specific serum antibody response was also measured. After challenge, viral shedding, weight loss, disease signs and death (only mice) were recorded. Results: Low-to-modest serum antibody titres were detected after vaccination. Nevertheless, the vaccine induced significant protection from disease after challenge with the wild-type virus. In the murine lethal challenge model, vaccination effectively prevented death and, furthermore, formulation with adjuvant reduced excessive weight loss and viral shedding. In ferrets, vaccination reduced viral shedding and protected against systemic spread of the virus. Conclusions: We have extended to the H7 subtype the finding that protective efficacy may not be directly correlated with the pre-challenge levels of serum antibodies, a finding which could be of great importance in assessing the potential effectiveness of pandemic influenza vaccines. © 2009 Blackwell Publishing Ltd.