Enhanced cross-protection against influenza viruses by vaccinatio | 7998
Virology & Mycology

Virology & Mycology
Open Access

ISSN: 2161-0517

Enhanced cross-protection against influenza viruses by vaccination with VLP coupling both matrix-2 ectodomain and hemagglutinin stalk domain

2nd International Conference on Flu

October 31-November 02, 2016 San Francisco, USA

I-Na Lu, Sophie Farinelle, Alex Ramirez, Mike Whelan, William Rosenberg and Claude P Muller

Luxembourg Institute of Health, Luxembourg
iQur Ltd, UK
University College London, UK

Posters & Accepted Abstracts: Virol Mycol

Abstract :

Vaccination with virus-like particles (VLPs) containing triple conserved matrix-2 ectodomain (VLP-3�?�?M2e) of influenza virus induces broader protection than the strain-specific protection afforded by conventional influenza vaccines. The broadly cross-protective immunity induced by those VLPs is known to be mediated by immune sera that can bind to Fc receptors on dendritic and macrophage cells. Here we present an approach to enhance the cross-protection by VLPs that express a conserved hemagglutinin (HA) stalk protein in addition to 3�?�?M2e, â�?�?VLP-3�?�?M2e-HAst.â�? Compared to VLP-3�?�?M2e, VLP-3�?�?M2e-HAst vaccination induces polyclonal antibodies against the conserved domains of two different surface antigens. This results in a stronger activation of the complement system that causes significantly more lysis of virus-infected A549 cells. Fluorescence microscopy reveals that the complement protein fragment C3b and C5b-9 colocalizes with the virus-bound antibodies on the surface of virus-infected A549 cells. In addition, we demonstrate that VLP-3�?�?M2e-HAst-induced polyclonal antibodies can bind both group 1 HA types: H1, H2, H5 and H9 as well as group 2 HA types: H3 and H7. VLP-3�?�?M2e-HAst vaccination prevents disease symptoms in mice without showing weight loss and confers complete cross protection against lethal challenge with the homologous influenza A virus, 2009 H1N1 pandemic virus and heterosubtypic H3N2 influenza virus. The results provide evidence that supplementation of M2e-based vaccines with HA stalk antigen is a promising approach for broadening cross-protection against influenza infection.

Biography :