A replicating modified vaccinia tiantan strain expressing an avian-derived influenza H5N1 hemagglutinin induce broadly neutralizing antibodies and cross-clade protective immunity in mice.

Abstract

To combat the possibility of a zoonotic H5N1 pandemic in a timely fashion, it is necessary to develop a vaccine that would confer protection against homologous and heterologous human H5N1 influenza viruses. Using a replicating modified vaccinia virus Tian Tan strain (MVTT) as a vaccine vector, we constructed MVTTHA-QH and MVTTHA-AH, which expresses the H5 gene of a goose-derived Qinghai strain A/Bar-headed Goose/Qinghai/1/2005 or human-derived Anhui Strain A/Anhui/1/2005. The immunogenicity profiles of both vaccine candidates were evaluated. Vaccination with MVTTHA-QH induced a significant level of neutralizing antibodies (Nabs) against a homologous strain and a wide range of H5N1 pseudoviruses (clades 1, 2.1, 2.2, 2.3.2, and 2.3.4). Neutralization tests (NT) and Haemagglutination inhibition (HI) antibodies inhibit the live autologous virus as well as a homologous A/Xingjiang/1/2006 and a heterologous A/Vietnam/1194/2004, representing two human isolates from clade 2.2 and clade 1, respectively. Importantly, mice vaccinated with intranasal MVTTHA-QH were completely protected from challenge with lethal dosages of A/Bar-headed Goose/Qinghai/1/2005 and the A/Viet Nam/1194/2004, respectively, but not control mice that received a mock MVTTS vaccine. However, MVTTHA-AH induced much lower levels of NT against its autologous strain. Our results suggest that it is feasible to use the H5 gene from A/Bar-headed Goose/Qinghai/1/2005 to construct an effective vaccine, when using MVTT as a vector, to prevent infections against homologous and genetically divergent human H5N1 influenza viruses.

• Authors: Haixia Xiao, Li Liu, Qingyu Zhu, Zhiwu Tan, Wenbo Yu, Xian Tang, Dawei Zhan, Yanhua Du, Haibo Wang, Di Liu, Zhixin Li, Kwok-Yung Yuen, David D Ho, George F Gao, Zhiwei Chen
• Journal: PloS one (PLoS One) Vol. 8 Issue 12 Pg. e83274 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 24358269 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Neutralizing
• Hemagglutinins

Topics

• Adaptive Immunity
• Animals
• Antibodies, Neutralizing (immunology, metabolism)
• Antibody Formation (genetics)
• Cells, Cultured
• Chick Embryo
• Cross Protection
• Dogs
• Female
• Hemagglutinins (genetics)
• Humans
• Influenza A Virus, H5N1 Subtype (genetics, immunology)
• Influenza, Human (immunology)
• Mice
• Mice, Inbred BALB C
• Organisms, Genetically Modified
• Orthomyxoviridae Infections (immunology)
• Vaccinia (immunology, virology)
• Vaccinia virus (genetics, immunology)
• Virus Replication