(512b) M2e Ligated to Elastin like Polypeptide Induces Protective Immunity Against Influenza A Virus

M2e ligated to elastin like
polypeptide induces protective immunity against influenza A
virus

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.

In this study we synthesized two different M2e-ELP constructs, the
first a monoblock ELP with a hydrophobic guest
residue, and the second a diblock ELP with a
hydrophilic and hydrophobic guest residue. The resulting molecules were
characterized via western blot and MALDI. The inverse transition temperatures
were also determined. It was found that attachment of M2e increased the transition
temperatures of the ELP molecules, but it was still below 37 C. Upon
vaccinating mice with M2e ligated to ELPs, along with CpG
as an adjuvant, it was found that a significantly high level of anti-M2e antibodies
could be stimulated in the serum. Subsequent challenge of vaccinated mice with
lethal influenza A virus (PR8) led to full protection
and lower body weight loss. Overall this study provides a proof-of-concept that
ELPs could serve as a carrier for M2e and have potential for development of a
universal influenza vaccine.