In Vivo Treatment with Insulin-like Growth Factor 1 Reduces CCR5 Expression on Vaccine-Induced Activated CD4+ T-Cells
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).
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 30, 2023
- Source ID
- 10.3390/vaccines11111662
Entities
People
- Anna Gutowska
- David C. Montefiori
- David J Venzon
- Dominic Paquin Proulx
- Genoveffa Franchini
- Georgia D. Tomaras
- Giacomo Gorini
- Guido Ferrari
- Hyoyoung Choo-wosoba
- Isabela Silva De Castro
- Joshua Kramer
- Kombo F. N’guessan
- Luca Schifanella
- Massimiliano Bissa
- Matthew W. Breed
- Melvin N. Doster
- Mohammad Arif Rahman
- Monica Vaccari
- Nicolò Binello
- Pamela A Kozlowski
- Ramona Moles
- Sarkis Sarkis
- Veronica Galli
- Xiaoying Shen
Organizations
- Duke University
- Henry M. Jackson Foundation for the Advancement of Military Medicine
- LSU Health Sciences Center New Orleans
- National Cancer Institute
- National Institute of Allergy and Infectious Diseases
- Office of AIDS Research
- Tulane University of Louisiana
- United States Army Medical Research Institute of Infectious Diseases
- United States Army Medical Research and Development Command
- United States Military HIV Research Program