In Vivo Treatment with Insulin-like Growth Factor 1 Reduces CCR5 Expression on Vaccine-Induced Activated CD4+ T-Cells
Year: 2023
Type: article
Abstract: At the heart of the DNA/ALVAC/gp120/alum vaccine’s efficacy in the absence of neutralizing antibodies is a delicate balance of pro- and anti-inflammatory immune responses that effectively decreases the risk of SIVmac251 acquisition in macaques. Vaccine efficacy is linked to antibodies recognizing the V2 helical conformation, DC-10 tolerogenic dendritic cells eliciting the clearance of apoptotic cells via efferocytosis, and CCR5 downregulation on vaccine-induced gut homing CD4+ cells. RAS activation is also linked to vaccine efficacy, which prompted the testing of IGF-1, a potent inducer of RAS activation with vaccination. We found that IGF-1 changed the hierarchy of V1/V2 epitope recognition and decreased both ADCC specific for helical V2 and efferocytosis. Remarkably, IGF-1 also reduced the expression of CCR5 on vaccine-induced CD4+ gut-homing T-cells, compensating for its negative effect on ADCC and efferocytosis and resulting in equivalent vaccine efficacy (71% with IGF-1 and 69% without).
Source: Vaccines
Authors: Massimiliano Bissa, Veronica Galli, Luca Schifanella, Monica Vaccari, Mohammad Arif Rahman, Giacomo Gorini, Nicolò Binello, Sarkis Sarkis, Anna Gutowska, Isabela Silva de Castro, Melvin N. Doster, Ramona Moles, Guido Ferrari, Xiaoying Shen, Georgia D. Tomaras, David C. Montefiori, Kombo F. N’guessan, Dominic Paquin-Proulx, Pamela A. Kozlowski, David J. Venzon, Hyoyoung Choo-Wosoba, Matthew W. Breed, Joshua Kramer, Genoveffa Franchini
Institutions: National Institutes of Health, National Cancer Institute, Tulane University, Duke University, Duke Medical Center, Henry M. Jackson Foundation, Walter Reed Army Institute of Research, Louisiana State University Health Sciences Center New Orleans, Center for Cancer Research, Leidos Biomedical Research Inc. (United States)
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,447
Funders: U.S. Department of Defense, U.S. Department of Health and Human Services, Sanofi, Ipsen Biopharmaceuticals, Ipsen, National Institutes of Health, Sanofi Pasteur, National Cancer Institute, National Institute of Allergy and Infectious Diseases, U.S. Army Medical Research Institute of Infectious Diseases, U.S. Army Medical Research and Development Command
OpenAlex ID: W4388094441