title: Ontogeny-based immunogens for the induction of V2-directed HIV broadly neutralizing antibodies.
abstract: The development of a preventative HIV vaccine able to elicit broadly neutralizing antibodies (bNAbs) remains a major challenge. Antibodies that recognize the V2 region at the apex of the HIV envelope trimer are among the most common bNAb specificities during chronic infection and many exhibit remarkable breadth and potency. Understanding the developmental pathway of these antibodies has provided insights into their precursors, and the viral strains that engage them, as well as defined how such antibodies mature to acquire breadth. V2-apex bNAbs are derived from rare precursors with long anionic CDR H3s that are often deleted in the B cell repertoire. However, longitudinal studies suggest that once engaged, these precursors contain many of the structural elements required for neutralization, and can rapidly acquire breadth through moderate levels of somatic hypermutation in response to emerging viral variants. These commonalities in the precursors and mechanism of neutralization have enabled the identification of viral strains that show enhanced reactivity for V2 precursors from multiple donors, and may form the basis of germline targeting approaches. In parallel, new structural insights into the HIV trimer, the target of these quaternary antibodies, has created invaluable new opportunities for ontogeny-based immunogens designed to select for rare V2-bNAb precursors, and drive them toward breadth.
authors.affiliation: Centre for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.|Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.|Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Penny L
authors.initials: PL
authors.lastname: Moore
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Gorman
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Doria-Rose
authors.affiliation: Centre for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.|Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.|Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Lynn
authors.initials: L
authors.lastname: Morris
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology*; D017637:Clonal Deletion; D022801:Complementarity Determining Regions / Q000235:genetics; D018095:Germ-Line Mutation / Q000235:genetics; D015483:HIV Antibodies / Q000378:metabolism*; D015488:HIV Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D055503:Protein Multimerization; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D022801:Complementarity Determining Regions; D015483:HIV Antibodies; D015488:HIV Antigens; D007143:Immunoglobulin Heavy Chains; D014759:Viral Envelope Proteins
keywords: 
  HIV
  ; V2-apex; broadly neutralizing antibodies; long CDR H3; ontogeny; trimeric immunogens