Broad Protection against Avian Influenza Virus by Using a Modified Vaccinia Ankara Virus Expressing a Mosaic Hemagglutinin Gene
Autor: | Attapon Kamlangdee, Tavis K. Anderson, Jorge E. Osorio, Tony L. Goldberg, Brock Kingstad-Bakke |
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Rok vydání: | 2014 |
Předmět: |
CD4-Positive T-Lymphocytes
Modified vaccinia Ankara Cross Protection Recombinant Fusion Proteins viruses Synthetic antigen Genetic Vectors Immunology Hemagglutinin (influenza) Hemagglutinin Glycoproteins Influenza Virus Vaccinia virus CD8-Positive T-Lymphocytes Biology Antibodies Viral medicine.disease_cause Microbiology H5N1 genetic structure Virus Antigenic drift chemistry.chemical_compound Influenza A Virus H1N1 Subtype Orthomyxoviridae Infections Virology Vaccines and Antiviral Agents medicine Animals Humans Drug Carriers Mice Inbred BALB C Vaccines Synthetic Influenza A Virus H5N1 Subtype Vaccination Antibodies Neutralizing Survival Analysis Influenza A virus subtype H5N1 Disease Models Animal chemistry Influenza Vaccines Insect Science biology.protein Vaccinia |
Zdroj: | Journal of Virology. 88:13300-13309 |
ISSN: | 1098-5514 0022-538X |
Popis: | 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. |
Databáze: | OpenAIRE |
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