HIV vaccines induce CD8 <sup>+</sup> T cells with low antigen receptor sensitivity-Reference-Cited by-同舟云学术

HIV vaccines induce CD8 ⁺ T cells with low antigen receptor sensitivity

Published:2023-12-15 Issue:6676 Volume:382 Page:1270-1276
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Migueles Stephen A.¹^ORCID,Nettere Danielle M.¹,Gavil Noah V.¹^ORCID,Wang Lawrence T.¹^ORCID,Toulmin Sushila A.¹,Kelly Elizabeth P.¹,Ward Addison J.¹^ORCID,Lin Siying¹^ORCID,Thompson Sarah A.¹,Peterson Bennett A.¹,Abdeen Cassidy S.¹,Sclafani Carina R.¹^ORCID,Pryal Patrick F.¹,Leach Benjamin G.¹,Ludwig Amanda K.¹^ORCID,Rogan Daniel C.¹,Przygonska Paulina A.¹,Cattani Angela¹^ORCID,Imamichi Hiromi¹^ORCID,Sachs Abraham²^ORCID,Cafri Gal²^ORCID,Huang Ning-Na¹^ORCID,Patamawenu Andy¹,Liang C. Jason³,Hallahan Claire W.³,Kambach Diane M.⁴,Han Edward X.⁵^ORCID,Coupet Tiffany⁵,Chen Jonathan⁵,Moir Susan L.¹^ORCID,Chun Tae-Wook¹^ORCID,Coates Emily E.⁶^ORCID,Ledgerwood Julie⁶,Schmidt Julien⁷⁸,Taillandier-Coindard Marie⁷⁸,Michaux Justine⁷⁸,Pak HuiSong⁷⁸,Bassani-Sternberg Michal⁷⁸^ORCID,Frahm Nicole⁹^ORCID,McElrath M. Juliana⁹^ORCID,Connors Mark¹^ORCID

Affiliation:

1. Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

2. Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

3. Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

4. Agilent Technologies, Inc., Santa Clara, CA, USA.

5. IsoPlexis, Inc., Branford, CT, USA.

6. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

7. Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland.

8. Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

9. Vaccine and Infectious Disease Division and the HIV Vaccine Trials Network, Fred Hutchinson Cancer Center, Seattle, WA, USA.

Abstract

Current HIV vaccines designed to stimulate CD8 + T cells have failed to induce immunologic control upon infection. The functions of vaccine-induced HIV-specific CD8 + T cells were investigated here in detail. Cytotoxic capacity was significantly lower than in HIV controllers and was not a consequence of low frequency or unaccumulated functional cytotoxic proteins. Low cytotoxic capacity was attributable to impaired degranulation in response to the low antigen levels present on HIV-infected targets. The vaccine-induced T cell receptor (TCR) repertoire was polyclonal and transduction of these TCRs conferred the same reduced functions. These results define a mechanism accounting for poor antiviral activity induced by these vaccines and suggest that an effective CD8 + T cell response may require a vaccination strategy that drives further TCR clonal selection.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Link

https://www.science.org/doi/pdf/10.1126/science.adg0514

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