Monocyte-derived transcriptome signature indicates antibody-dependent cellular phagocytosis as a potential mechanism of vaccine-induced protection against HIV-1

• Authors: Shida Shangguan, Walter Reed Army Institute of Research; Philip K Ehrenberg, Walter Reed Army Institute of Research; Aviva Geretz, Walter Reed Army Institute of Research; Lauren Yum, Walter Reed Army Institute of Research; Gautam Kundu, Walter Reed Army Institute of Research; Kelly May, Walter Reed Army Institute of Research; Slim Fourati, Emory University; Krystelle Nganou-Makamdop, Vaccine Research Center, NIH, Bethesda; LaTonya D Williams, Duke University; Sheetal Sawant, Duke University; Eric Lewitus, Walter Reed Army Institute of Research; Punnee Pitisuttithum, Mahidol University; Sorachai Nitayaphan, Armed Forces Research Institute of Medical Sciences; Suwat Chariyalertsak, Chiang Mai University; Supachai Rerks-Ngarm, Ministry of Public Health, Nonthaburi; Morgane Rolland, Henry M. Jackson Foundation for the Advancement of Military Medicine; Daniel C Douek, Vaccine Research Center, NIH, Bethesda; Peter Gilbert, Fred Hutchinson Cancer Research Center; Georgia D Tomaras, Duke University; Nelson L Michael, Walter Reed Army Institute of Research; Sandhya Vasan, Walter Reed Army Institute of Research; Rasmi Thomas, Walter Reed Army Institute of Research
• Journal Title: ELIFE
• Volume: Volume 10
• Publisher: eLIFE SCIENCES PUBL LTD | 2021-09-17
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.7554/eLife.69577.sa2
• Subjects: Health Sciences, Medicine and Surgery
• Keywords: Science & Technology; Life Sciences & Biomedicine; Biology; Life Sciences & Biomedicine - Other Topics; HIV vaccine; transcriptomics; single cell; CITE-seq; vaccine efficacy; ADCP; Human; Rhesus macaque; RNA-SEQ; EFFICACY; CHALLENGES; RECEPTOR; IMPACT; TRIAL; ALVAC; RISK

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.