Characterization of a Bivalent Vaccine Capable of Inducing Protection Against Both Ebola and Cross-clade H5N1 Influenza in Mice.

Abstract

BACKGROUND:

Ebola virus (EBOV) is a lethal pathogen that causes up to 90% mortality in humans, whereas H5N1 avian influenza has a 60% fatality rate. Both viruses are considered pandemic threats. The objective was to evaluate the protective efficacy of a bivalent, recombinant vesicular stomatitis virus vaccine expressing both the A/Hanoi/30408/2005 H5N1 hemagglutinin and the EBOV glycoprotein (VSVΔG-HA-ZGP) in a lethal mouse model of infection.

METHODS:

Mice were vaccinated 28 days before or 30 minutes after a lethal challenge with mouse-adapted EBOV or selected H5N1 influenza viruses from clades 0, 1, and 2. Animals were monitored for weight loss and survival, in addition to humoral and cell-mediated responses after immunization.

RESULTS:

A single VSVΔG-HA-ZGP injection was efficacious when administered 28 days before a homologous H5N1 and/or mouse-adapted EBOV challenge, as well as a heterologous H5N1 challenge. Postexposure protection was only observed in vaccinated animals challenged with homologous H5N1 and/or mouse-adapted EBOV. Analysis of the adaptive immune response postvaccination revealed robust specific T- and B-cell responses, including a potent hemagglutinin inhibition antibody response against all H5N1 strains tested.

CONCLUSIONS:

The results highlight the ability of vesicular stomatitis virus-vectored vaccines to rapidly confer protection against 2 unrelated pathogens and stimulate cross-protection against H5N1 influenza viruses.

• Authors: Gary Wong, Xiangguo Qiu, Hideki Ebihara, Heinz Feldmann, Gary P Kobinger
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 212 Suppl 2 Pg. S435-42 (Oct 01 2015) ISSN: 1537-6613 [Electronic] United States
• PMID: 26022441 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
• Copyright: © Crown copyright 2015.

Chemical References

• Antibodies, Viral
• Hemagglutinins
• Viral Vaccines

Topics

• Adaptive Immunity (immunology)
• Animals
• Antibodies, Viral (immunology)
• Chlorocebus aethiops
• Cross Protection (immunology)
• Dogs
• Ebolavirus (immunology)
• Female
• HEK293 Cells
• Hemagglutinins (immunology)
• Hemorrhagic Fever, Ebola (immunology)
• Humans
• Influenza A Virus, H5N1 Subtype (immunology)
• Influenza, Human (immunology)
• Madin Darby Canine Kidney Cells
• Mice
• Mice, Inbred BALB C
• Orthomyxoviridae Infections (immunology)
• Vaccination (methods)
• Vero Cells
• Vesiculovirus (immunology)
• Viral Vaccines (immunology)