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Title: HIV-1 Envelope Glycoproteins from Diverse Clades Differentiate Antibody Responses and Durability among Vaccinees

Journal Article · · Journal of Virology
DOI:https://doi.org/10.1128/jvi.01843-17· OSTI ID:1626074
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  1. Duke Univ., Durham, NC (United States). School of Medicine. Duke Human Vaccine Inst.; Duke Univ., Durham, NC (United States). School of Medicine. Dept. of Medicine
  2. Fred Hutchinson Cancer Research Center, Seattle, WA (United States). Statistical Center for HIV/AIDS Research and Prevention. Vaccine and Infectious Disease Division
  3. Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Biology and Biophysics
  4. Rutgers Univ., Newark, NJ (United States). New Jersey Medical School. Public Health Research Inst.
  5. Thailand Ministry of Public Health, Bangkok (Thailand). Department of Disease Control
  6. Mahidol Univ., Bangkok (Thailand). Vaccine Trial Center
  7. Armed Forces Research Inst. of Medical Sciences, Bangkok (Thailand)
  8. Univ. of California, Santa Cruz, CA (United States). Dept. of Biomedical Engineering
  9. Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD (United States); Walter Reed Army Inst. of Research, Silver Spring, MD (United States). US Military HIV Research Program
  10. Univ. of Lusanne (Switzerland). Lausanne Univ. Hospital. Swiss Vaccine Research Inst. Dept. of Medicine. Service of Infecitous Diseases. Service of Immunology and Allergy
  11. Icahn School of Medicine at Mount Sinai, New York, NY (United States)
  12. Duke Univ., Durham, NC (United States). School of Medicine. Duke Human Vaccine Inst.; Duke Univ., Durham, NC (United States). School of Medicine. Dept. of Medicine; Duke Univ., Durham, NC (United States). School of Medicine. Dept. of Immunology
  13. Duke Univ., Durham, NC (United States). School of Medicine. Duke Human Vaccine Inst.; Duke Univ., Durham, NC (United States). School of Medicine. Dept. of Surgery
  14. Duke Univ., Durham, NC (United States). School of Medicine. Duke Human Vaccine Inst.; Duke Univ., Durham, NC (United States). School of Medicine. Dept. of Immunology; Duke Univ., Durham, NC (United States). School of Medicine. Dept. of Surgery; Duke Univ., Durham, NC (United States). School of Medicine. Dept. of Molecular Genetics and Microbiology
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Induction of broadly cross-reactive antiviral humoral responses with the capacity to target globally diverse circulating strains is a key goal for HIV-1 immunogen design. A major gap in the field is the identification of diverse HIV-1 envelope antigens to evaluate vaccine regimens for binding antibody breadth. In this study, we define unique antigen panels to map HIV-1 vaccine-elicited antibody breadth and durability. Diverse HIV-1 envelope glycoproteins were selected based on genetic and geographic diversity to cover the global epidemic, with a focus on sexually acquired transmitted/founder viruses with a tier 2 neutralization phenotype. Unique antigenicity was determined by nonredundancy (Spearman correlation), and antigens were clustered using partitioning around medoids (PAM) to identify antigen diversity. Cross-validation demonstrated that the PAM method was better than selection by reactivity and random selection. Analysis of vaccine-elicited V1V2 binding antibody in longitudinal samples from the RV144 clinical trial revealed the striking heterogeneity among individual vaccinees in maintaining durable responses. These data support the idea that a major goal for vaccine development is to improve antibody levels, breadth, and durability at the population level. Elucidating the level and durability of vaccine-elicited binding antibody breadth needed for protection is critical for the development of a globally efficacious HIV vaccine.

Research Organization:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
Grant/Contract Number:
AC52-06NA25396
OSTI ID:
1626074
Journal Information:
Journal of Virology, Vol. 92, Issue 8; ISSN 0022-538X
Publisher:
American Society for MicrobiologyCopyright Statement
Country of Publication:
United States
Language:
English

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  • The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/f6s9-vz03
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Cited By (9)

Immunogenicity of NYVAC Prime-Protein Boost Human Immunodeficiency Virus Type 1 Envelope Vaccination and Simian-Human Immunodeficiency Virus Challenge of Nonhuman Primates journal February 2018
Methods for comparing durability of immune responses between vaccine regimens in early-phase trials journal January 2019
Landscapes of binding antibody and T-cell responses to pox-protein HIV vaccines in Thais and South Africans journal January 2020
Glycosylation in health and disease journal March 2019
HIV vaccine delayed boosting increases Env variable region 2–specific antibody effector functions journal January 2020
Immune correlates of the Thai RV144 HIV vaccine regimen in South Africa journal September 2019
Towards conformational fidelity of a quaternary HIV-1 epitope: computational design and directed evolution of a minimal V1V2 antigen journal April 2018
Antibody Fc effector functions and IgG3 associate with decreased HIV-1 risk journal October 2019
HIV-1 vaccination by needle-free oral injection induces strong mucosal immunity and protects against SHIV challenge journal February 2019

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Related Subjects

60 APPLIED LIFE SCIENCES
virology
humoral immunity
antibody
antigenicity
vaccine
HIV-1
diversity
durability