Antibody-Mediated Protective Mechanisms Induced by a Trivalent Parainfluenza Virus-Vectored Ebolavirus Vaccine

Author:

Kimble J. Brian12,Malherbe Delphine C.12,Meyer Michelle12,Gunn Bronwyn M.3,Karim Marcus M.3,Ilinykh Philipp A.12,Iampietro Mathieu12,Mohamed Khaled S.12,Negi Surendra4,Gilchuk Pavlo5,Huang Kai12,Wolf Yuri I.6,Braun Werner4,Crowe James E.578ORCID,Alter Galit3,Bukreyev Alexander129

Affiliation:

1. Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA

2. Galveston National Laboratory, Galveston, Texas, USA

3. Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, USA

4. Department of Biochemistry and Molecular Biology, Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, Texas, USA

5. Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA

6. National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, USA

7. Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA

8. Department of Pediatrics (Infectious Diseases), Vanderbilt University Medical Center, Nashville, Tennessee, USA

9. Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, Texas, USA

Abstract

The symptoms of the disease caused by the ebolaviruses Ebola, Bundibugyo, and Sudan are similar, and their areas of endemicity overlap. However, because of the limited antigenic relatedness of the ebolavirus glycoprotein (GP) used in all candidate vaccines against these viruses, they protect only against homologous and not against heterologous ebolaviruses. Therefore, a broadly specific pan-ebolavirus vaccine is required, and this might be achieved by administration of a cocktail of vaccines. The effects of cocktail administration of ebolavirus vaccines on the antibody repertoire remain unknown. Here, an in-depth analysis of the antibody responses to administration of a cocktail of human parainfluenza virus type 3-vectored vaccines against individual ebolaviruses was performed, which included analysis of binding to GP, neutralization of individual ebolaviruses, epitope specificity, Fc-mediated functions, and protection against the three ebolaviruses. The results demonstrated potent and balanced responses against individual ebolaviruses and no significant reduction of the responses compared to that induced by individual vaccines.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

DOD | Defense Threat Reduction Agency

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

Reference60 articles.

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2. Kuhn JH. 2008. Filoviruses, 1st ed. Springer, Vienna, Austria.

3. Feldmann H, Sanchez A, Geisbert TW. 2013. Filoviridae: Marburg and Ebola viruses, p. 923–956. In Knipe DM, Howley PM, Cohen JI, Griffin DE, Lamb RA, Martin MA, Racaniello VR, Roizman B (ed.), Fields virology, 6th ed. Lippincott Williams & Wilkins, Philadelphia, PA.

4. Transmission of Ebola virus (Zaire strain) to uninfected control monkeys in a biocontainment laboratory

5. Lethal experimental infections of rhesus monkeys by aerosolized Ebola virus;Johnson E;Int J Exp Pathol,1995

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