M2e Ligated to Elastin like Polypeptide Induces Protective Immunity Against Influenza A Virus

摘要

With seasonal influenza epidemics leading to remarkable mortality and morbidity throughout the globe, and posing a continuous threat of another pandemic, the influenza virus is considered one of the most deadly human pathogen. In contrast to current vaccines, which are based on the two dominant influenza virus surface glycoproteins - hemagglutinin (HA) and neuraminidase (NA), recent effort has been devoted towards development of a universal influenza vaccine based on the highly conserved sequence of the extracellular region of an influenza membrane protein called M2e. An M2e-based vaccine could offer broader protection against different influenza strains, in contrast to the narrow protection provided by HA and NA-based vaccines. Research done in the past has shown that immunogenicity of M2e can be greatly enhanced by linking M2e, a comparatively smaller antigen, to an appropriate carrier. With this in mind, we wanted to investigate the use of elastin-like polypeptides (ELPs) as an approach to enhance the immunogenicity of M2e. ELPs contain a repeat sequence of ?GXGVP', where 'X' can be any amino acid except proline, and have been shown to be biocompatible and biodegradable in nature. ELPs also exhibit an inverse transition behaviour wherein they precipitate above a certain critical temperature. Thus we hypothesized that M2e-ELPs when designed to precipitate below the body temperature could provide a particulate stimulus to the immune system, and might offer a better alternative to certain carriers such as human papillomavirus, hepatitis B virus core subunit, and keyhole limpet hemocyanin.