Monocyte-derived transcriptome signature indicates antibody-dependent cellular phagocytosis as a potential mechanism of vaccine-induced protection against HIV-1
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 C Douek,
Peter Gilbert,
Georgia D Tomaras,
Nelson L Michael,
Sandhya Vasan,
Rasmi Thomas
Affiliations
Shida Shangguan
US Military HIV Research Program (MHRP), Walter Reed Army Institute of Research, Silver Spring, United States; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, United States
US Military HIV Research Program (MHRP), Walter Reed Army Institute of Research, Silver Spring, United States
Aviva Geretz
US Military HIV Research Program (MHRP), Walter Reed Army Institute of Research, Silver Spring, United States; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, United States
Lauren Yum
US Military HIV Research Program (MHRP), Walter Reed Army Institute of Research, Silver Spring, United States; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, United States
Gautam Kundu
US Military HIV Research Program (MHRP), Walter Reed Army Institute of Research, Silver Spring, United States; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, United States
Kelly May
US Military HIV Research Program (MHRP), Walter Reed Army Institute of Research, Silver Spring, United States; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, United States
Department of Pathology and Laboratory Medicine, Emory University, Atlanta, United States
Krystelle Nganou-Makamdop
Vaccine Research Center, NIH, Bethesda, United States
LaTonya D Williams
Departments of Surgery, Immunology and Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, United States
Sheetal Sawant
Departments of Surgery, Immunology and Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, United States
Eric Lewitus
US Military HIV Research Program (MHRP), Walter Reed Army Institute of Research, Silver Spring, United States; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, United States
Punnee Pitisuttithum
Vaccine Trial Centre, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
Sorachai Nitayaphan
Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand
Suwat Chariyalertsak
Research Institute for Health Sciences and Faculty of Public Health, Chiang Mai University, Chiang Mai, Thailand
Supachai Rerks-Ngarm
Department of Disease Control, Ministry of Public Health, Nonthaburi, Thailand
Morgane Rolland
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, United States
Daniel C Douek
Vaccine Research Center, NIH, Bethesda, United States
Peter Gilbert
Fred Hutchinson Cancer Research Center, Seattle, United States
Georgia D Tomaras
Departments of Surgery, Immunology and Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, United States
Nelson L Michael
US Military HIV Research Program (MHRP), Walter Reed Army Institute of Research, Silver Spring, United States
Sandhya Vasan
US Military HIV Research Program (MHRP), Walter Reed Army Institute of Research, Silver Spring, United States; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, United States
A gene signature was previously found to be correlated with mosaic adenovirus 26 vaccine protection in simian immunodeficiency virus and simian-human immunodeficiency virus challenge models in non-human primates. In this report, we investigated the 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 (VE). 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 VE represents a tool both to identify potential mechanisms, as with ADCP here, and to screen novel approaches to accelerate the development of new vaccine candidates.