Monocyte-derived transcriptome signature indicates antibody-dependent cellular phagocytosis as a potential mechanism of vaccine-induced protection against HIV-1
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Abstract
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.
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Phagocytosis-related genes FCER1G, FCGR2A, TYROBP, and GAS6 are down-regulated in AD monocytes compared with AC monocytes, indicating a reduced ability of AD monocytes to phagocytose Aβ.
“We found that the expression of phagocytosis-related genes, including FCER1G, FCGR2A, TYROBP, and GAS6 (46–48), was down-regulated in AD monocytes as compared to AC monocytes (Fig. 3C), indicating a reduced ability of AD monocytes to phagocytose Aβ.”
From Understanding monocyte-driven neuroinflammation in Alzheimer’s disease using human cortical organoid microphysiological systems (2025) · cites this paper as [47]
The Results section (page unavailable) identifies TYROBP as a phagocytosis-pathway gene, and the Discussion describes its role in promoting phagocytosis. Our copy does not establish FCER1G, FCGR2A, or GAS6 as phagocytosis-related genes. The AD-versus-AC expression finding is presented as the citing authors’ own result, not as a finding attributed to this source. (LLM, conf=0.86)
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Laderoute, M. P. (2024) · Preprints.org · doi:10.20944/preprints202312.0185.v2 · Cited by 1 · see citing works
Ehrenberg, P. K., Geretz, A., Volčič, M., Izumi, T., Yum, L. K., Waickman, A. T., Shangguan, S., Paquin‐Proulx, D., Creegan, M., Bose, M., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.11.12.623270 · Cited by 1 · see citing works
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Self-citationThe importance of phagocytosis and its effect on the immune system
Gençoğlu, H. S., Aydemir, E., & Ayaz, F. (2026) · Molecular Biology Reports · doi:10.1007/s11033-026-11917-5
- Authors
- Shangguan, S., Ehrenberg, P. K., Geretz, A., Yum, L., Kundu, G., May, K., Fourati, S., Nganou-Makamdop, K., Williams, L. D., Sawant, S., Lewitus, E., Pitisuttithum, P., Nitayaphan, S., Chariyalertsak, S., Rerks-Ngarm, S., Rolland, M., Douek, D. C., Gilbert, P., Tomaras, G. D., Michael, N. L., Vasan, S., & Thomas, R.
- Affiliations
- Henry M. Jackson Foundation (US)
- Walter Reed Army Institute of Research (US)
- Emory University (US)
- Vaccine Research Center, NIH
- Duke University (US)
- US Military HIV Research Program (MHRP), Walter Reed Army Institute of Research
- Mahidol University (TH)
- Armed Forces Research Institute of Medical Science (TH)
- Chiang Mai University (TH)
- Department of Disease Control, Ministry of Public Health
- National Institutes of Health (US)
- Fred Hutch Cancer Center (US)
- Corresponding author
- Thomas, Rasmi
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2021-09-17
- Volume
- 10
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC8514236
- OpenAlex
- W3199927989
- Cited by
- 26
- References
- 59
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 6 · 2023: 3 · 2022: 6 · 2021: 1
- FWCI
- 2.25
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Henry M. Jackson Foundation (W81XWH-07-2-0067)
- National Institute of Allergy and Infectious Diseases
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS Research and Interventions
- Keywords
- HIV-1 vaccine, antibody-dependent cellular phagocytosis, vaccine-induced protection, RV144 trial, vaccine efficacy, correlates of protection, CITE-seq, myeloid cells, single-cell transcriptomics
- MeSH terms
- Immunogenicity, Vaccine, RNA-Seq, Clinical Trials as Topic, Humans, Monocytes, Phagocytosis, Time Factors, Vaccination, HIV Antibodies, HIV-1, HIV Infections, Treatment Outcome, AIDS Vaccines, Vaccines, DNA, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Databases, Genetic, Host-Pathogen Interactions, Single-Cell Analysis, Transcriptome
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