title: Unique safety issues associated with virus-vectored vaccines: Potential for and theoretical consequences of recombination with wild type virus strains.
abstract: In 2003 and 2013, the World Health Organization convened informal consultations on characterization and quality aspects of vaccines based on live virus vectors. In the resulting reports, one of several issues raised for future study was the potential for recombination of virus-vectored vaccines with wild type pathogenic virus strains. This paper presents an assessment of this issue formulated by the Brighton Collaboration. To provide an appropriate context for understanding the potential for recombination of virus-vectored vaccines, we review briefly the current status of virus-vectored vaccines, mechanisms of recombination between viruses, experience with recombination involving live attenuated vaccines in the field, and concerns raised previously in the literature regarding recombination of virus-vectored vaccines with wild type virus strains. We then present a discussion of the major variables that could influence recombination between a virus-vectored vaccine and circulating wild type virus and the consequences of such recombination, including intrinsic recombination properties of the parent virus used as a vector; sequence relatedness of vector and wild virus; virus host range, pathogenesis and transmission; replication competency of vector in target host; mechanism of vector attenuation; additional factors potentially affecting virulence; and circulation of multiple recombinant vectors in the same target population. Finally, we present some guiding principles for vector design and testing intended to anticipate and mitigate the potential for and consequences of recombination of virus-vectored vaccines with wild type pathogenic virus strains.
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Condit
authors.affiliation: Institute of Infectious Disease and Molecular Medicine, University of Cape Town and National Health Laboratory Service, Cape Town, South Africa.
authors.forename: Anna-Lise
authors.initials: AL
authors.lastname: Williamson
authors.affiliation: Independent Adviser (formerly of NIAID, NIH, Bethesda, MD 20893, USA).
authors.forename: Rebecca
authors.initials: R
authors.lastname: Sheets
authors.affiliation: Department of Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA; St. Giles Laboratory of Human Genetics of Infectious Diseases, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Seligman
authors.affiliation: Kleiner Perkins Caufield & Byers, Menlo Park, CA 94025, USA.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Monath
authors.affiliation: US Military HIV Research Program (MHRP), Bethesda, MD 20817, USA (formerly of International AIDS Vaccine Initiative, New York, NY 10004, USA).
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Excler
authors.affiliation: PaxVax Inc., 900 Veterans Boulevard, Ste 500, San Diego, CA 92121, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Gurwith
authors.affiliation: National Vaccine Program Office, Office of the Assistant Secretary for Health (OASH), U.S. Department of Health and Human Services, Washington, DC 20201, USA.
authors.forename: Karin
authors.initials: K
authors.lastname: Bok
authors.affiliation: Independent Adviser (formerly of National Institute for Biological Standards and Control, Potters Bar, EN6 3QG, UK).
authors.forename: James S
authors.initials: JS
authors.lastname: Robertson
authors.affiliation: Takeda Vaccines, Inc., One Takeda Parkway, Deerfield, IL 60015, USA.
authors.forename: Denny
authors.initials: D
authors.lastname: Kim
authors.affiliation: Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP), Centers for Disease Control and Prevention (CDC), Atlanta, GA 30333, USA.
authors.forename: R
authors.initials: R
authors.lastname: Michael Hendry
authors.affiliation: Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP), Centers for Disease Control and Prevention (CDC), Atlanta, GA 30333, USA. Electronic address: brightoncollaborationv3swg@gmail.com.
authors.forename: Vidisha
authors.initials: V
authors.lastname: Singh
authors.affiliation: Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP), Centers for Disease Control and Prevention (CDC), Atlanta, GA 30333, USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Mac
authors.affiliation: Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP), Centers for Disease Control and Prevention (CDC), Atlanta, GA 30333, USA.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Chen
mesh_terms: D000818:Animals; D004337:Drug Carriers; D005822:Genetic Vectors; D006801:Humans; D011995:Recombination, Genetic; D014613:Vaccines, Attenuated / Q000009:adverse effects / Q000235:genetics; D014765:Viral Vaccines / Q000009:adverse effects* / Q000235:genetics*; D014774:Virulence; D014780:Viruses
chemical_list: D004337:Drug Carriers; D014613:Vaccines, Attenuated; D014765:Viral Vaccines
keywords: Brighton Collaboration; Live viral vaccines; Potential for recombination; Vaccine manufacturing; Vaccine safety; Vaccines; Virus recombination