Intranasal immunization with a chimeric influenza antigen delivered by detoxified anthrax toxin induces broad spectrum immunity against influenza viruses (TECH2P.756)

Abstract

Influenza remains to be a significant public health problem worldwide, despite the heavy campaign for flu vaccination in many countries. The conventional influenza vaccines are based on stimulating immune responses against hemagglutinin by virus attenuation or inactivation. However, they must be reformulated annually because of antigenic shift and drift of circulating influenza viral strains. These seasonal vaccines do not always match the circulating strains, and there is the ever-present threat that avian influenza viruses may adapt to be transmitted in humans. Development of a broadly protective or universal influenza vaccine would have a significant impact on public health. We constructed a new chimeric influenza antigen, which is composed of the relatively conserved matrix protein 2 (M2) and stem region of hemagglutinin (HA2) of influenza A viruses in combination with a detoxified anthrax edema toxin delivery system. This vaccine candidate has been shown to elicit T cell and humoral responses against influenza antigens and cross-strain protective immunity against influenza viruses, when it is intranasally delivered to mice. In addition, the vaccination of CD4+ and CD8+ T cell knock out mice do not protect against influenza virus infection. Thus, this novel vaccine strategy induces the CD4+ and CD8+ memory T cell responses which play an important role in cross-strain protection against influenza viruses.