Vaccines (Oct 2023)
In Vivo Treatment with Insulin-like Growth Factor 1 Reduces CCR5 Expression on Vaccine-Induced Activated CD4<sup>+</sup> 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
Affiliations
- Massimiliano Bissa
- Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD 20892, USA
- Veronica Galli
- Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD 20892, USA
- Luca Schifanella
- Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD 20892, USA
- Monica Vaccari
- Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD 20892, USA
- Mohammad Arif Rahman
- Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD 20892, USA
- Giacomo Gorini
- Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD 20892, USA
- Nicolò Binello
- Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD 20892, USA
- Sarkis Sarkis
- Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD 20892, USA
- Anna Gutowska
- Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD 20892, USA
- Isabela Silva de Castro
- Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD 20892, USA
- Melvin N. Doster
- Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD 20892, USA
- Ramona Moles
- Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD 20892, USA
- Guido Ferrari
- Division of Surgical Sciences, Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA
- Xiaoying Shen
- Division of Surgical Sciences, Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA
- Georgia D. Tomaras
- Division of Surgical Sciences, Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA
- David C. Montefiori
- Division of Surgical Sciences, Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA
- Kombo F. N’guessan
- US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
- Dominic Paquin-Proulx
- US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
- Pamela A. Kozlowski
- Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
- David J. Venzon
- Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
- Hyoyoung Choo-Wosoba
- Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
- Matthew W. Breed
- Laboratory Animal Sciences Program, Leidos Biomedical Research Inc., Frederick National Laboratory, Frederick, MD 21701, USA
- Joshua Kramer
- Laboratory Animal Sciences Program, Leidos Biomedical Research Inc., Frederick National Laboratory, Frederick, MD 21701, USA
- Genoveffa Franchini
- Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD 20892, USA
- DOI
- https://doi.org/10.3390/vaccines11111662
- Journal volume & issue
-
Vol. 11,
no. 11
p. 1662
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).
Keywords
