title: The Live Attenuated Cholera Vaccine CVD 103-HgR Primes Responses to the Toxin-Coregulated Pilus Antigen TcpA in Subjects Challenged with Wild-Type Vibrio cholerae.
abstract: One potential advantage of live attenuated bacterial vaccines is the ability to stimulate responses to antigens which are only expressed during the course of infection. To determine whether the live attenuated cholera vaccine CVD 103-HgR (Vaxchora) results in antibody responses to the in vivo-induced toxin-coregulated pilus antigen TcpA, we measured IgA and IgG responses to Vibrio cholerae O1 El Tor TcpA in a subset of participants in a recently reported experimental challenge study. Participants were challenged with V. cholerae O1 El Tor Inaba N16961 either 10 days or 90 days after receiving the vaccine or a placebo. Neither vaccination nor experimental infection with V. cholerae alone resulted in a robust TcpA IgG or IgA response, but each did elicit a strong response to cholera toxin. However, compared to placebo recipients, vaccinees had a marked increase in IgG TcpA antibodies following the 90-day challenge, suggesting that vaccination with CVD 103-HgR resulted in priming for a subsequent response to TcpA. No such difference between vaccine and placebo recipients was observed for volunteers challenged 10 days after vaccination, indicating that this was insufficient time for vaccine-induced priming of the TcpA response. The priming of the response to TcpA and potentially other antigens expressed in vivo by attenuated V. cholerae may have relevance to the maintenance of immunity in areas where cholera is endemic.
authors.affiliation: Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Mayo-Smith
authors.affiliation: Merck & Co., Inc., Kenilworth, New Jersey, USA.
authors.forename: Jakub K
authors.initials: JK
authors.lastname: Simon
authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Wilbur H
authors.identifier: http://orcid.org/0000-0001-7741-5536
authors.initials: WH
authors.lastname: Chen
authors.affiliation: PaxVax, Inc., Redwood City, California, USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: Haney
authors.affiliation: PaxVax, Inc., Redwood City, California, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Lock
authors.affiliation: Department of Medicine, Unit of Infectious Disease and Vaccine Testing Center, University of Vermont College of Medicine, Burlington, Vermont, USA.
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Lyon
authors.affiliation: Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA.|Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Calderwood
authors.affiliation: Department of Medicine, Unit of Infectious Disease and Vaccine Testing Center, University of Vermont College of Medicine, Burlington, Vermont, USA.
authors.forename: Beth D
authors.initials: BD
authors.lastname: Kirkpatrick
authors.affiliation: Cincinnati Children's Hospital Medical Center and the Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.|Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Cohen
authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Myron M
authors.initials: MM
authors.lastname: Levine
authors.affiliation: PaxVax, Inc., Redwood City, California, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Gurwith
authors.affiliation: Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA jbharris@mgh.harvard.edu.|Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Jason B
authors.initials: JB
authors.lastname: Harris
mesh_terms: D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood*; D000942:Antigens, Bacterial / Q000276:immunology; D002771:Cholera / Q000276:immunology / Q000517:prevention & control*; D022121:Cholera Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D004311:Double-Blind Method; D005260:Female; D036781:Fimbriae Proteins / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D010919:Placebos / Q000008:administration & dosage; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D041241:Vibrio cholerae O1 / Q000276:immunology*; D014838:Volunteers
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D022121:Cholera Vaccines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D010919:Placebos; C085807:TcpA protein, Vibrio cholerae; D014613:Vaccines, Attenuated; C414990:cholera vaccine CVD 103-HgR; D036781:Fimbriae Proteins
keywords: TcpA; challenge; cholera; priming; vaccines