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Definition of the viral targets of protective HIV-1-specific T cell responses

Journal Article · · Journal of Translational Medicine
 [1];  [2];  [2];  [3];  [4];  [2];  [2];  [5];  [6];  [7];  [2];  [8];  [9];  [5];  [3];  [10];  [11];  [12];  [13];  [14] more »;  [15];  [7];  [16];  [16];  [17];  [18];  [19];  [20];  [21];  [5];  [8] « less
  1. Irsicaixa AIDS Research Institute-HIVACAT, Badalona (Spain); ’Lluita contra la SIDA’ Foundation, Hospital Germans Trias i Pujol, Badalona (Spain); Universitat Autònoma de Barcelona (Spain); DOE/OSTI
  2. Irsicaixa AIDS Research Institute-HIVACAT, Badalona (Spain)
  3. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
  4. ’Lluita contra la SIDA’ Foundation, Hospital Germans Trias i Pujol, Badalona (Spain)
  5. Asociación Civil IMPACTA Salud y Educacion, Lima (Peru)
  6. Irsicaixa AIDS Research Institute-HIVACAT, Badalona (Spain); Universitat Politècnica de Catalunya, Barcelona (Spain). Dept. Estadística i Investigació Operativa
  7. Harvard and MIT, Boston, MA (United States). Ragon Institute of MGH
  8. Irsicaixa AIDS Research Institute-HIVACAT, Badalona (Spain); Institucio Catalana de Recerca i Estudis Avançats (ICREA), Barcelona (Spain)
  9. MHRP, Frederick, MD (United States)
  10. Univ. of Oklahoma, Oklahoma City, OK (United States). Medical Center
  11. Univ. of California, Los Angeles, CA (United States)
  12. Services of Immunology and Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS)-AIDS Research Group-HIVACAT, Hospital Clinic, Barcelona (Spain)
  13. British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC (Canada)
  14. British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC (Canada); Simon Fraser Univ., Burnaby, BC (Canada)
  15. Miscrosoft Research, Redmond, WA (United States)
  16. Univ. of Washington, Seattle, WA (United States). Dept. of Microbiology
  17. Nuffield Department of Medicine, Oxford (United Kingdom). Dept. of Paediatrics; Univ. of KwaZulu-Natal, Durban (South Africa). HIV Pathogenesis Program. DDMRI
  18. Harvard and MIT, Boston, MA (United States). Ragon Institute of MGH; Univ. of KwaZulu-Natal, Durban (South Africa). HIV Pathogenesis Program. DDMRI; Howard Hughes Medical Inst., Chevy Chase, MD (United States)
  19. Services of Immunology and Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS)-AIDS Research Group-HIVACAT, Hospital Clinic, Barcelona (Spain)
  20. Irsicaixa AIDS Research Institute-HIVACAT, Badalona (Spain); ’Lluita contra la SIDA’ Foundation, Hospital Germans Trias i Pujol, Badalona (Spain)
  21. Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Santa Fe Inst. (SFI), Santa Fe, NM (United States)
+ Show Author Affiliations
Background: The efficacy of the CTL component of a future HIV-1 vaccine will depend on the induction of responses with the most potent antiviral activity and broad HLA class I restriction. However, current HIV vaccine designs are largely based on viral sequence alignments only, not incorporating experimental data on T cell function and specificity. Methods: Here, 950 untreated HIV-1 clade B or -C infected individuals were tested for responses to sets of 410 overlapping peptides (OLP) spanning the entire HIV-1 proteome. For each OLP, a “protective ratio” (PR) was calculated as the ratio of median viral loads (VL) between OLP non-responders and responders. Results: For both clades, there was a negative relationship between the PR and the entropy of the OLP sequence. There was also a significant additive effect of multiple responses to beneficial OLP. Responses to beneficial OLP were of significantly higher functional avidity than responses to non-beneficial OLP. They also had superior in-vitro antiviral activities and, importantly, were at least as predictive of individuals’ viral loads than their HLA class I genotypes. Conclusions: The data thus identify immunogen sequence candidates for HIV and provide an approach for T cell immunogen design applicable to other viral infections.
Research Organization:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Organization:
National Institutes of Health (NIH); USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
Grant/Contract Number:
AC52-06NA25396
OSTI ID:
1626582
Journal Information:
Journal of Translational Medicine, Journal Name: Journal of Translational Medicine Journal Issue: 1 Vol. 9; ISSN 1479-5876
Publisher:
BioMed CentralCopyright Statement
Country of Publication:
United States
Language:
English

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Gag and env conserved element CE DNA vaccines elicit broad cytotoxic T cell responses targeting subdominant epitopes of HIV and SIV Able to recognize virus-infected cells in macaques journal July 2018
Defining kinetic properties of HIV-specific CD8+ T-cell responses in acute infection journal November 2017
Polyvalent vaccine approaches to combat HIV-1 diversity journal January 2017
Effects of Mutations on Replicative Fitness and Major Histocompatibility Complex Class I Binding Affinity Are Among the Determinants Underlying Cytotoxic-T-Lymphocyte Escape of HIV-1 Gag Epitopes journal December 2017
FARMS: A New Algorithm for Variable Selection journal January 2015
Development of prophylactic vaccines against HIV-1 journal January 2013
Can immunotherapy be useful as a “functional cure” for infection with Human Immunodeficiency Virus-1? journal September 2012
Increased T cell breadth and antibody response elicited in prime-boost regimen by viral vector encoded homologous SIV Gag/Env in outbred CD1 mice journal December 2016
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HIV-1 p24gag Derived Conserved Element DNA Vaccine Increases the Breadth of Immune Response in Mice journal March 2013
Superior Control of HIV-1 Replication by CD8+ T Cells Targeting Conserved Epitopes: Implications for HIV Vaccine Design journal May 2013
Fitness Costs of Mutations at the HIV-1 Capsid Hexamerization Interface journal June 2013
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HIV-1 Vaccine-Induced T-Cell Reponses Cluster in Epitope Hotspots that Differ from Those Induced in Natural Infection with HIV-1 journal June 2013
Coupling of HIV-1 Antigen to the Selective Autophagy Receptor SQSTM1/p62 Promotes T-Cell-Mediated Immunity journal May 2016
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Latency reversal and viral clearance to cure HIV-1 text January 2016
Delivery of HIV-1 Polyepitope Constructs Using Cationic and Amphipathic Cell Penetrating Peptides into Mammalian Cells journal January 2020
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Harnessing CD8+ T Cells Under HIV Antiretroviral Therapy journal February 2019
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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
HIV specific CTL
HLA
Research & Experimental Medicine
clade B
clade C
entropy
epitope
functional avidity
immune correlate
vaccine immunogen design