title: Human antibody repertoire after VSV-Ebola vaccination identifies novel targets and virus-neutralizing IgM antibodies.
abstract: Development of an effective vaccine against Ebola virus is of high priority. However, knowledge about potential correlates of protection and the durability of immune response after vaccination is limited. Here, we elucidate the human antibody repertoire after administration of vesicular stomatitis virus (VSV)-Ebola vaccine at 3 million, 20 million and 100 million plaque-forming units (PFU) and homologous VSV-Ebola vaccine boost in healthy adult volunteers. Whole genome-fragment phage display libraries, expressing linear and conformational epitopes of Ebola glycoprotein (GP), showed higher diversity of antibody epitopes in individuals vaccinated with 20 million PFU than in those vaccinated with 3 million or 100 million PFU. Surface plasmon resonance kinetics showed higher levels of GP-binding antibodies after a single vaccination with 20 million or 100 million PFU than with 3 million PFU, and these correlated strongly with neutralization titers. A second vaccination did not boost antibody or virus neutralization titers, which declined rapidly, and induced only minimal antibody affinity maturation. Isotype analysis revealed a predominant IgM response even after the second vaccination, which contributed substantially to virus neutralization in vitro. These findings may help identify new vaccine targets and aid development and evaluation of effective countermeasures against Ebola.
authors: Division of Viral Products, Center for Biologics Evaluation and Research (CBER), US Food and Drug Administration, Silver Spring, Maryland, USA.
authors: Surender
authors: S
authors: Khurana
authors: Division of Viral Products, Center for Biologics Evaluation and Research (CBER), US Food and Drug Administration, Silver Spring, Maryland, USA.
authors: Sandra
authors: S
authors: Fuentes
authors: Division of Viral Products, Center for Biologics Evaluation and Research (CBER), US Food and Drug Administration, Silver Spring, Maryland, USA.
authors: Elizabeth M
authors: EM
authors: Coyle
authors: Division of Viral Products, Center for Biologics Evaluation and Research (CBER), US Food and Drug Administration, Silver Spring, Maryland, USA.
authors: Supriya
authors: S
authors: Ravichandran
authors: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors: Richard T
authors: RT
authors: Davey
authors: Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
authors: John H
authors: JH
authors: Beigel
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D046129:Ebola Vaccines / Q000008:administration & dosage*; D029043:Ebolavirus / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005260:Female; D006023:Glycoproteins / Q000276:immunology; D064368:Healthy Volunteers; D006801:Humans; D000071497:Immunogenicity, Vaccine; D007075:Immunoglobulin M / Q000276:immunology*; D008297:Male; D014613:Vaccines, Attenuated / Q000008:administration & dosage; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D046129:Ebola Vaccines; D000939:Epitopes; D006023:Glycoproteins; D007075:Immunoglobulin M; D014613:Vaccines, Attenuated