Broad protection against avian influenza virus by using a modified vaccinia Ankara virus expressing a mosaic hemagglutinin gene.

Abstract

UNLABELLED:

A critical failure in our preparedness for an influenza pandemic is the lack of a universal vaccine. Influenza virus strains diverge by 1 to 2% per year, and commercially available vaccines often do not elicit protection from one year to the next, necessitating frequent formulation changes. This represents a major challenge to the development of a cross-protective vaccine that can protect against circulating viral antigenic diversity. We have constructed a recombinant modified vaccinia virus Ankara (MVA) that expresses an H5N1 mosaic hemagglutinin (H5M) (MVA-H5M). This mosaic was generated in silico using 2,145 field-sourced H5N1 isolates. A single dose of MVA-H5M provided 100% protection in mice against clade 0, 1, and 2 avian influenza viruses and also protected against seasonal H1N1 virus (A/Puerto Rico/8/34). It also provided short-term (10 days) and long-term (6 months) protection postvaccination. Both neutralizing antibodies and antigen-specific CD4(+) and CD8(+) T cells were still detected at 5 months postvaccination, suggesting that MVA-H5M provides long-lasting immunity.

IMPORTANCE:

Influenza viruses infect a billion people and cause up to 500,000 deaths every year. A major problem in combating influenza is the lack of broadly effective vaccines. One solution from the field of human immunodeficiency virus vaccinology involves a novel in silico mosaic approach that has been shown to provide broad and robust protection against highly variable viruses. Unlike a consensus algorithm which picks the most frequent residue at each position, the mosaic method chooses the most frequent T-cell epitopes and combines them to form a synthetic antigen. These studies demonstrated that a mosaic influenza virus H5 hemagglutinin expressed by a viral vector can elicit full protection against diverse H5N1 challenges as well as induce broader immunity than a wild-type hemagglutinin.

• Authors: Attapon Kamlangdee, Brock Kingstad-Bakke, Tavis K Anderson, Tony L Goldberg, Jorge E Osorio
• Journal: Journal of virology (J Virol) Vol. 88 Issue 22 Pg. 13300-9 (Nov 2014) ISSN: 1098-5514 [Electronic] United States
• PMID: 25210173 (Publication Type: Journal Article)
• Copyright: Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Chemical References

• Antibodies, Neutralizing
• Antibodies, Viral
• Drug Carriers
• Hemagglutinin Glycoproteins, Influenza Virus
• Influenza Vaccines
• Recombinant Fusion Proteins
• Vaccines, Synthetic
• hemagglutinin, avian influenza A virus

Topics

• Animals
• Antibodies, Neutralizing (blood)
• Antibodies, Viral (blood)
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Cross Protection
• Disease Models, Animal
• Drug Carriers (administration & dosage)
• Genetic Vectors
• Hemagglutinin Glycoproteins, Influenza Virus (genetics, immunology)
• Humans
• Influenza A Virus, H1N1 Subtype (immunology)
• Influenza A Virus, H5N1 Subtype (genetics, immunology)
• Influenza Vaccines (administration & dosage, genetics, immunology)
• Mice, Inbred BALB C
• Orthomyxoviridae Infections (prevention & control)
• Recombinant Fusion Proteins (genetics, immunology)
• Survival Analysis
• Vaccination (methods)
• Vaccines, Synthetic (administration & dosage, genetics, immunology)
• Vaccinia virus (genetics)