Prime-Boost Interval Matters: A Randomized Phase 1 Study to Identify the Minimum Interval Necessary to Observe the H5 DNA Influenza Vaccine Priming Effect

(See the Brief Report by Khurana et al on pages 413–7.) Influenza is a worldwide public health burden, and despite the availability of vaccines, improved strategies for inducing durable and broad immunity remain a high priority. Highly pathogenic strains, such as influenza A(H5N1), present an additional challenge in that transmissibility is variable, the H5 antigen is not highly immunogenic, and the severity of disease and mortality rate are significant when human infection does occur [1]. The World Health Organization maintains data on human H5N1 cases [2], and although, to date, there have been <1000 documented human cases and none of the H5N1 circulating viruses have been highly transmissible in humans, 2 studies performed by independent teams suggest there is potential for increased transmissibility between mammals through genetic alterations that could also occur in the wild [3, 4]. Although the epidemiologic and clinical characteristics of H5N1 infection present a difficult challenge for public health policy makers, the absence of the confounding effect of baseline immunity to H5N1 in the population allows researchers to evaluate novel influenza vaccine strategies utilizing the H5 antigen. DNA influenza vaccines have been shown to induce cross-neutralizing antibodies, with some of those directed against the conserved region of the hemagglutinin (HA) stem in clinical trials [5], and are protective against infection from multiple strains of influenza in animal models [6]. Additionally, H5 DNA priming enhances the overall humoral immune response to inactivated influenza vaccine, specifically when the boost interval is increased from 4 to 24 weeks [5]. We describe further evaluation of H5 DNA priming for an H5N1 monovalent inactivated vaccine (MIV) boost with prime-boost intervals of 4, 8, 12, 16, and 24 weeks.