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

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Title: HIV vaccines induce CD8+ T cells with low antigen receptor sensitivity.
Authors: Migueles, Stephen A., Nettere, Danielle M., Gavil, Noah V., Wang, Lawrence T., Toulmin, Sushila A., Kelly, Elizabeth P., Ward, Addison J., Siying Lin, Thompson, Sarah A., Peterson, Bennett A., Abdeen, Cassidy S., Sclafani, Carina R., Pryal, Patrick F., Leach, Benjamin G., Ludwig, Amanda K., Rogan, Daniel C., Przygonska, Paulina A., Cattani, Angela, Imamichi, Hiromi, Sachs, Abraham
Source: Science (pre-March 2025). 12/15/2023, Vol. 382 Issue 6676, p1270-1276. 7p. 5 Graphs.
Subjects: Antigen receptors, T cells, AIDS vaccines, CD8 antigen, T cell receptors
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. [ABSTRACT FROM AUTHOR]
Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: HIV vaccines induce CD8<superscript>+</superscript> T cells with low antigen receptor sensitivity.
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  Data: <searchLink fieldCode="AR" term="%22Migueles%2C+Stephen+A%2E%22">Migueles, Stephen A.</searchLink><br /><searchLink fieldCode="AR" term="%22Nettere%2C+Danielle+M%2E%22">Nettere, Danielle M.</searchLink><br /><searchLink fieldCode="AR" term="%22Gavil%2C+Noah+V%2E%22">Gavil, Noah V.</searchLink><br /><searchLink fieldCode="AR" term="%22Wang%2C+Lawrence+T%2E%22">Wang, Lawrence T.</searchLink><br /><searchLink fieldCode="AR" term="%22Toulmin%2C+Sushila+A%2E%22">Toulmin, Sushila A.</searchLink><br /><searchLink fieldCode="AR" term="%22Kelly%2C+Elizabeth+P%2E%22">Kelly, Elizabeth P.</searchLink><br /><searchLink fieldCode="AR" term="%22Ward%2C+Addison+J%2E%22">Ward, Addison J.</searchLink><br /><searchLink fieldCode="AR" term="%22Siying+Lin%22">Siying Lin</searchLink><br /><searchLink fieldCode="AR" term="%22Thompson%2C+Sarah+A%2E%22">Thompson, Sarah A.</searchLink><br /><searchLink fieldCode="AR" term="%22Peterson%2C+Bennett+A%2E%22">Peterson, Bennett A.</searchLink><br /><searchLink fieldCode="AR" term="%22Abdeen%2C+Cassidy+S%2E%22">Abdeen, Cassidy S.</searchLink><br /><searchLink fieldCode="AR" term="%22Sclafani%2C+Carina+R%2E%22">Sclafani, Carina R.</searchLink><br /><searchLink fieldCode="AR" term="%22Pryal%2C+Patrick+F%2E%22">Pryal, Patrick F.</searchLink><br /><searchLink fieldCode="AR" term="%22Leach%2C+Benjamin+G%2E%22">Leach, Benjamin G.</searchLink><br /><searchLink fieldCode="AR" term="%22Ludwig%2C+Amanda+K%2E%22">Ludwig, Amanda K.</searchLink><br /><searchLink fieldCode="AR" term="%22Rogan%2C+Daniel+C%2E%22">Rogan, Daniel C.</searchLink><br /><searchLink fieldCode="AR" term="%22Przygonska%2C+Paulina+A%2E%22">Przygonska, Paulina A.</searchLink><br /><searchLink fieldCode="AR" term="%22Cattani%2C+Angela%22">Cattani, Angela</searchLink><br /><searchLink fieldCode="AR" term="%22Imamichi%2C+Hiromi%22">Imamichi, Hiromi</searchLink><br /><searchLink fieldCode="AR" term="%22Sachs%2C+Abraham%22">Sachs, Abraham</searchLink>
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  Data: <searchLink fieldCode="JN" term="%22Science+%28pre-March+2025%29%22">Science (pre-March 2025)</searchLink>. 12/15/2023, Vol. 382 Issue 6676, p1270-1276. 7p. 5 Graphs.
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  Data: <searchLink fieldCode="DE" term="%22Antigen+receptors%22">Antigen receptors</searchLink><br /><searchLink fieldCode="DE" term="%22T+cells%22">T cells</searchLink><br /><searchLink fieldCode="DE" term="%22AIDS+vaccines%22">AIDS vaccines</searchLink><br /><searchLink fieldCode="DE" term="%22CD8+antigen%22">CD8 antigen</searchLink><br /><searchLink fieldCode="DE" term="%22T+cell+receptors%22">T cell receptors</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: 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. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=174225086
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        Value: 10.1126/science.adg0514
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        Text: English
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      – SubjectFull: AIDS vaccines
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      – TitleFull: HIV vaccines induce CD8+ T cells with low antigen receptor sensitivity.
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              Text: 12/15/2023
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