In Vivo Treatment with Insulin-like Growth Factor 1 Reduces CCR5 Expression on Vaccine-Induced Activated CD4+ T-Cells

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

doi:10.3390/vaccines11111662

In Vivo Treatment with Insulin-like Growth Factor 1 Reduces CCR5 Expression on Vaccine-Induced Activated CD4⁺ T-Cells

Vaccines (Basel). 2023 Oct 30;11(11):1662. doi: 10.3390/vaccines11111662.

Authors

Massimiliano Bissa¹, Veronica Galli¹, Luca Schifanella¹, Monica Vaccari^{1

2}, Mohammad Arif Rahman¹, Giacomo Gorini¹, Nicolò Binello¹, Sarkis Sarkis¹, Anna Gutowska¹, Isabela Silva de Castro¹, Melvin N Doster¹, Ramona Moles¹, Guido Ferrari³, Xiaoying Shen³, Georgia D Tomaras³, David C Montefiori³, Kombo F N'guessan^{4

5}, Dominic Paquin-Proulx^{4

5}, Pamela A Kozlowski⁶, David J Venzon⁷, Hyoyoung Choo-Wosoba⁷, Matthew W Breed⁸, Joshua Kramer⁸, Genoveffa Franchini¹

Affiliations

¹ Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD 20892, USA.
² Tulane National Primate Center & School of Medicine, Tulane University, Covington, LA 70118, USA.
³ Division of Surgical Sciences, Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA.
⁴ US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
⁵ Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA.
⁶ Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
⁷ Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
⁸ Laboratory Animal Sciences Program, Leidos Biomedical Research Inc., Frederick National Laboratory, Frederick, MD 21701, USA.

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 SIV_mac251 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).

Keywords: CCR5; CD4; HIV; IGF-1; SIV; T-cells; insulin-like growth factor.

Abstract

Grants and funding