Post-exposure vaccination against influenza (132.4)

Abstract

Abstract Vaccines currently licensed for the prevention of influenza induce antibodies against the influenza hemagglutinin (HA) and neuraminidase (NA) contained in the vaccine preparation but require at least two weeks after immunization for the development of protective immunity. We have developed a novel vaccine based on recombinant vesicular stomatitis virus which expresses the influenza hemagglutinin (rVSV HA) and protects mice from lethal influenza challenge when the vaccine is administered intramuscularly shortly after delivery of the influenza challenge virus. To our knowledge ours is the first vaccine which effectively protects animals from lethal influenza challenge when delivered by a systemic route after influenza exposure has occurred. The mechanism(s) by which rVSV HA protects remain to be determined but induction of HA-specific immune responses is essential, because animals immunized with an empty rVSV vector were not protected equally. Our data are consistent with a model in which post-exposure rVSV HA vaccination induces an immediate antiviral cytokine response, followed by expansion of HA-specific cytotoxic CD8 T cells, which circulate to the respiratory tract and clear infected cells. Vaccinated animals do not have detectable serum neutralizing Ab to influenza during the acute phase of the infection, but antibody may be required at later timepoints for complete clearance of influenza.