Induction of Cross-Clade Antibody and T-Cell Responses by a Modified Vaccinia Virus Ankara–Based Influenza A(H5N1) Vaccine in a Randomized Phase 1/2a Clinical Trial
| Autor: | Mart M. Lamers, Stella E. van Trierum, Arwen F. Altenburg, Nella J. Nieuwkoop, Joost H. C. M. Kreijtz, Albert D. M. E. Osterhaus, Marion Koopmans, Mathilde Richard, Gerd Sutter, Ron A. M. Fouchier, David F. Nieuwenhuijse, Rory D. de Vries, Erwin de Bruin, Mark Pronk, Guus F. Rimmelzwaan |
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| Přispěvatelé: | Virology |
| Rok vydání: | 2018 |
| Předmět: |
Adult
Male 0301 basic medicine T-Lymphocytes Orthomyxoviridae Protein Array Analysis Hemagglutinin (influenza) Hemagglutinin Glycoproteins Influenza Virus Vaccinia virus Cross Reactions Antibodies Viral medicine.disease_cause Virus Young Adult Major Articles and Brief Reports 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine SDG 3 - Good Health and Well-being Double-Blind Method Neutralization Tests Influenza Human Influenza A virus medicine Antigenic variation Humans Immunology and Allergy 030212 general & internal medicine Immunization Schedule Drug Carriers Vaccines Synthetic Hemagglutination assay Influenza A Virus H5N1 Subtype biology Antibody-Dependent Cell Cytotoxicity Hemagglutination Inhibition Tests biology.organism_classification Virology Influenza A virus subtype H5N1 3. Good health 030104 developmental biology Infectious Diseases chemistry Influenza Vaccines biology.protein Female Vaccinia |
| Zdroj: | Journal of Infectious Diseases, 218(4), 614-623. Oxford University Press |
| ISSN: | 1537-6613 0022-1899 |
| Popis: | BACKGROUND: High-pathogenicity avian influenza viruses continue to circulate in poultry and wild birds and occasionally infect humans, sometimes with fatal outcomes. Development of vaccines is a priority to prepare for potential pandemics but is complicated by antigenic variation of the surface glycoprotein hemagglutinin. We report the immunological profile induced by human immunization with modified vaccinia virus Ankara (MVA) expressing the hemagglutinin gene of influenza A(H5N1) virus A/Vietnam/1194/04 (rMVA-H5). METHODS: In a double-blinded phase 1/2a clinical trial, 79 individuals received 1 or 2 injections of rMVA-H5 or vector control. Twenty-seven study subjects received a booster immunization after 1 year. The breadth, magnitude, and properties of vaccine-induced antibody and T-cell responses were characterized. RESULTS: rMVA-H5 induced broadly reactive antibody responses, demonstrated by protein microarray, hemagglutination inhibition, virus neutralization, and antibody-dependent cellular cytotoxicity assays. Antibodies cross-reacted with antigenically distinct H5 viruses, including the recently emerged subtypes H5N6 and H5N8 and the currently circulating subtype H5N1. In addition, the induction of T cells specific for H5 viruses of 2 different clades was demonstrated. CONCLUSIONS: rMVA-H5 induced immune responses that cross-reacted with H5 viruses of various clades. These findings validate rMVA-H5 as vaccine candidate against antigenically distinct H5 viruses. CLINICAL TRIALS REGISTRATION: NTR3401. |
| Databáze: | OpenAIRE |
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