A DNA vaccine that targets hemagglutinin to antigen-presenting cells protects mice against H7 influenza

Zoonotic influenza H7 viral infections have a case fatality rate of about 40%. 26 Currently no or limited human to human spread has occurred, but we may be facing a 27 severe pandemic threat if the virus acquires the ability to transmit between humans. 28 Novel vaccines that can be rapidly produced for global distribution are urgently 29 needed, and DNA vaccines may be the only type of vaccine that allows for the speed 30 necessary to quench an emerging pandemic. Here, we have constructed DNA 31 vaccines encoding the hemagglutinin (HA) from influenza A/chicken/Italy/13474/99 32 (H7N1). In order to increase the efficacy of DNA vaccination, HA was targeted to 33 either major histocompatibility complex (MHC) class II molecules or chemokine 34 receptors 1, 3 and 5 (CCR1/3/5) that are expressed on antigen presenting cells (APC). 35 A single DNA vaccination with APC -targeted HA significantly increased antibody 36 levels in sera, as compared to non -targeted control vaccines. The antibodies were 37 confirmed neutralizing in an H7 pseudotype -based neutralization assay. Furthermore, 38 the APC -targeted vaccines increased the levels of antigen -specific cytotoxic T -cells, 39 and a single DNA vaccination could confer protection against a lethal challenge with 40 influenza A/turkey/Italy/3889/1999 (H7N1) in mice. In conclusion, we have 41 developed a vaccine that rapidly could contribute protection against a pandemic threat 42 from avian influenza.