Multiclade Human Immunodeficiency Virus Type 1 Envelope Immunogens Elicit Broad Cellular and Humoral Immunity in Rhesus Monkeys
Michael S. Seaman,Ling Xu,Kristin Beaudry,Kristi L. Martin,Margaret H. Beddall,Ayako Miura,Anna Sambor,Bimal K. Chakrabarti,Yue Huang,Robert T. Bailer,Richard A. Koup,John R. Mascola,Gary J. Nabel,Norman L. Letvin,Norman L. Letvin +14 more
TLDR
It is demonstrated that it is possible to generate protective immune responses by vaccination with genetically diverse isolates of HIV-1 and suggested that a multicomponent vaccine encoding Env proteins from multiple clades of HIV -1 can generate broad Env-specific T-lymphocyte and antibody responses without antigenic interference.Abstract:
The development of a human immunodeficiency virus type 1 (HIV-1) vaccine that elicits potent cellular and humoral immune responses recognizing divergent strains of HIV-1 will be critical for combating the global AIDS epidemic. The present studies were initiated to examine the magnitude and breadth of envelope (Env)-specific T-lymphocyte and antibody responses generated by vaccines containing either a single or multiple genetically distant HIV-1 Env immunogens. Rhesus monkeys were immunized with DNA prime-recombinant adenovirus boost vaccines encoding a Gag-Pol-Nef polyprotein in combination with either a single Env or a mixture of clade-A, clade-B, and clade-C Envs. Monkeys receiving the multiclade Env immunization developed robust immune responses to all vaccine antigens and, importantly, a greater breadth of Env recognition than monkeys immunized with vaccines including a single Env immunogen. All groups of vaccinated monkeys demonstrated equivalent immune protection following challenge with the pathogenic simian-human immunodeficiency virus 89.6P. These data suggest that a multicomponent vaccine encoding Env proteins from multiple clades of HIV-1 can generate broad Env-specific T-lymphocyte and antibody responses without antigenic interference. This study demonstrates that it is possible to generate protective immune responses by vaccination with genetically diverse isolates of HIV-1.read more
Citations
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Polyvalent vaccines for optimal coverage of potential T-cell epitopes in global HIV-1 variants.
Will Fischer,Simon Perkins,James Theiler,Tanmoy Bhattacharya,Tanmoy Bhattacharya,Karina Yusim,Robert Funkhouser,Carla Kuiken,Barton F. Haynes,Norman L. Letvin,Bruce D. Walker,Beatrice H. Hahn,Bette T. Korber,Bette T. Korber +13 more
TL;DR: It was found that coverage of viral diversity using mosaics was greatly increased compared to coverage by natural-sequence vaccine candidates, for both variable and conserved proteins; for conserved HIV-1 proteins, global coverage may be feasible.
Journal ArticleDOI
Preserved CD4+ central memory T cells and survival in vaccinated SIV-challenged monkeys.
Norman L. Letvin,John R. Mascola,Yue Sun,Darci A. Gorgone,Adam P. Buzby,Ling Xu,Zhi Yong Yang,Bimal K. Chakrabarti,Srinivas S. Rao,Jörn E. Schmitz,David C. Montefiori,Brianne R. Barker,Fred L. Bookstein,Gary J. Nabel +13 more
TL;DR: Although these monkeys demonstrated a reduction in viremia restricted to the early phase of SIV infection, they showed a prolonged survival that could be predicted by the magnitude of the vaccine-induced cellular immune response, which should guide the evaluation of AIDS vaccines in humans.
Journal ArticleDOI
Human Immunodeficiency Virus Type 1 Subtype Distribution in the Worldwide Epidemic: Pathogenetic and Therapeutic Implications
TL;DR: A review of the genetic diversity of HIV-1 can be found in this article, with particular emphasis on its pathogenetic and therapeutic implications, as well as the potential for vaccine development.
Journal ArticleDOI
Toll-like receptor agonists influence the magnitude and quality of memory T cell responses after prime-boost immunization in nonhuman primates
Ulrike Wille-Reece,Barbara J. Flynn,Karin Loré,Richard A. Koup,Aaron P. Miles,Allan Saul,Ross M. Kedl,Joseph J. Mattapallil,Walter R. Weiss,Mario Roederer,Robert A. Seder +10 more
TL;DR: In animals vaccinated with HIV Gag protein/Montanide and CpG ODN or the TLR7/8 agonist, the presence and type of TLR adjuvant used during primary immunization conferred stability and dramatically influenced the magnitude and quality of the Th1 and CD8+ T cell responses after the rAD-Gag boost.
Journal ArticleDOI
Structural basis for diverse N-glycan recognition by HIV-1–neutralizing V1–V2–directed antibody PG16
Marie Pancera,Syed Shahzad-ul-Hussan,Nicole A. Doria-Rose,Jason S. McLellan,Robert T. Bailer,Kaifan Dai,Sandra Loesgen,Mark K. Louder,Ryan P. Staupe,Yongping Yang,Baoshan Zhang,Robert Parks,Joshua Eudailey,Krissey E. Lloyd,Julie Blinn,S. Munir Alam,Barton F. Haynes,Mohammed N. Amin,Lai-Xi Wang,Dennis R. Burton,Wayne C. Koff,Gary J. Nabel,John R. Mascola,Carole A. Bewley,Peter D. Kwong +24 more
TL;DR: The structure of antibody PG16 bound to a scaffolded V1–V2 is reported, showing an epitope comprising both high mannose–type and complex-type N-linked glycans, and can provide clues to guide the design of modified antibodies with enhanced neutralization.
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