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In simian-human immunodeficiency virus (SHIV)-infected non-human primates, broadly neutralizing antibodies (bNAbs) against the virus appear to stimulate T cell immunity. To determine whether this phenomenon also occurs in humans we measured HIV-1-specific cellular immunity longitudinally in individuals with HIV-1 starting antiviral therapy (ART) with or without adjunctive bNAb 3BNC117 treatment. Using the activation-induced marker (AIM) assay and interferon-γ release, we observe that frequencies of Pol- and Gag-specific CD8+ T cells, as well as Gag-induced interferon-γ responses, are significantly higher among individuals that received adjunctive 3BNC117 compared to ART-alone at 3 and 12 months after starting ART. The observed changes in cellular immunity were directly correlated to pre-treatment 3BNC117-sensitivity. Notably, increased HIV-1-specific immunity is associated with partial or complete ART-free virologic control during treatment interruption for up to 4 years. Our findings suggest that bNAb treatment at the time of ART initiation maintains HIV-1-specific CD8+ T cell responses that are associated with ART-free virologic control.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 6473 |
| Tidsskrift | Nature Communications |
| Vol/bind | 13 |
| ISSN | 2041-1723 |
| DOI | |
| Status | Udgivet - okt. 2022 |
Funding Information:
We thank all study participants who devoted time to our research as well as every clinical research unit involved in the study. We acknowledge Rockefeller University for providing 3BNC117 as well as Bristol-Myers Squibb Company (Celgene Corporation) for providing the romidepsin. We acknowledge Data-Set-Go ( www.data-set-go.dk ) for analyzing env sequences using “bNAb-ReP” algorithm developed by VRC/NIH for 3BNC117 sensitivity prediction. We thank LabCorp Monogram Biosciences for performing the PhenoSense analyses. Finally, we would like to acknowledge the amazing support and help by the late Amin Alamshah, a kind and brilliant clinical project manager for the Imperial College Centre for Translational and Experimental Medicine, who tragically lost his life prior to the completion of this study. The study was funded by the Danish Council for Independent Research (grants #7016-00022 and #9060-00023B), Central Region Denmark Research Fund, The Danish Regions’ Medicine and Treatment Fund, and Next Experimental Therapy Partnership. Research reported in this publication was also supported by the National Institute Of Allergy And Infectious Diseases of the National Institutes of Health under Award Number UM1AI164565. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Study drugs were donated free of charge by The Rockefeller University (3BNC117) and Celgene (romidepsin) for use in this trial. N.N.K. is supported by a Vanier Scholarship from the Canadian Institutes for Health Research (CIHR). Z.L.B. is supported by a scholar award from the Michael Smith Foundation for Health Research.
Publisher Copyright:
© 2022, The Author(s).
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