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Title: | Monocyte-derived transcriptome signature indicates antibody-dependent cellular phagocytosis as a potential mechanism of vaccine-induced protection against hiv-1 |
Authors: | Shida Shangguan Philip K. Ehrenberg Aviva Geretz Lauren Yum Gautam Kundu Kelly May Slim Fourati Krystelle Nganou-Makamdop Latonya D. Williams Sheetal Sawant Eric Lewitus Punnee Pitisuttithum Sorachai Nitayaphan Suwat Chariyalertsak Supachai Rerks-Ngarm Morgane Rolland Daniel Douek Peter Gilbert Georgia D. Tomaras Nelson Michael Sandhya Vasan Rasmi Thomas |
Authors: | Shida Shangguan Philip K. Ehrenberg Aviva Geretz Lauren Yum Gautam Kundu Kelly May Slim Fourati Krystelle Nganou-Makamdop Latonya D. Williams Sheetal Sawant Eric Lewitus Punnee Pitisuttithum Sorachai Nitayaphan Suwat Chariyalertsak Supachai Rerks-Ngarm Morgane Rolland Daniel Douek Peter Gilbert Georgia D. Tomaras Nelson Michael Sandhya Vasan Rasmi Thomas |
Keywords: | Biochemistry, Genetics and Molecular Biology;Immunology and Microbiology;Neuroscience |
Issue Date: | 1-Sep-2021 |
Abstract: | A gene signature previously correlated with mosaic adenovirus 26 vaccine protection in simian immunodeficiency virus (SIV) and SHIV challenge models in non-human primates (NHP). In this report we investigated presence of this signature as a correlate of reduced risk in human clinical trials and potential mechanisms of protection. The absence of this gene signature in the DNA/rAd5 human vaccine trial, which did not show efficacy, strengthens our hypothesis that this signature is only enriched in studies that demonstrated protection. This gene signature was enriched in the partially effective RV144 human trial that administered the ALVAC/protein vaccine, and we find that the signature associates with both decreased risk of HIV-1 acquisition and increased vaccine efficacy. Total RNA-seq in a clinical trial that used the same vaccine regimen as the RV144 HIV vaccine implicated antibody-dependent cellular phagocytosis (ADCP) as a potential mechanism of vaccine protection. CITE-seq profiling of 53 surface markers and transcriptomes of 53,777 single cells from the same trial showed that genes in this signature were primarily expressed in cells belonging to the myeloid lineage, including monocytes, which are major effector cells for ADCP. The consistent association of this transcriptome signature with vaccine efficacy represents a tool both to identify potential mechanisms, as with ADCP here, and to screen novel approaches to accelerate development of new vaccine candidates. |
URI: | https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85116328012&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/75565 |
ISSN: | 2050084X |
Appears in Collections: | CMUL: Journal Articles |
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