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

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. VenzonHyoyoung Choo-Wosoba, Matthew W. Breed, Joshua Kramer, Genoveffa Franchini

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

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).

Original language	English
Article number	1662
Journal	Vaccines
Volume	11
Issue number	11
DOIs	https://doi.org/10.3390/vaccines11111662
State	Published - Nov 2023
Externally published	Yes

Scopus Subject Areas

Immunology
Pharmacology
Drug Discovery
Infectious Diseases
Pharmacology (medical)

Keywords

CCR5
CD4
HIV
IGF-1
insulin-like growth factor
SIV
T-cells

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.3390/vaccines11111662

Cite this

Bissa, M., Galli, V., Schifanella, L., Vaccari, M., Rahman, M. A., Gorini, G., Binello, N., Sarkis, S., Gutowska, A., Silva de Castro, I., Doster, M. N., Moles, R., Ferrari, G., Shen, X., Tomaras, G. D., Montefiori, D. C., N’guessan, K. F., Paquin-Proulx, D., Kozlowski, P. A., ... Franchini, G. (2023). In Vivo Treatment with Insulin-like Growth Factor 1 Reduces CCR5 Expression on Vaccine-Induced Activated CD4⁺ T-Cells. Vaccines, 11(11), Article 1662. https://doi.org/10.3390/vaccines11111662

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title = "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{\textquoteright}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 = "CCR5, CD4, HIV, IGF-1, insulin-like growth factor, SIV, T-cells",

author = "Massimiliano Bissa and Veronica Galli and Luca Schifanella and Monica Vaccari and Rahman, {Mohammad Arif} and Giacomo Gorini and Nicol{\`o} Binello and Sarkis Sarkis and Anna Gutowska and {Silva de Castro}, Isabela and Doster, {Melvin N.} and Ramona Moles and Guido Ferrari and Xiaoying Shen and Tomaras, {Georgia D.} and Montefiori, {David C.} and N{\textquoteright}guessan, {Kombo F.} and Dominic Paquin-Proulx and Kozlowski, {Pamela A.} and Venzon, {David J.} and Hyoyoung Choo-Wosoba and Breed, {Matthew W.} and Joshua Kramer and Genoveffa Franchini",

note = "Publisher Copyright: {\textcopyright} 2023 by the authors.",

year = "2023",

month = nov,

doi = "10.3390/vaccines11111662",

language = "English",

volume = "11",

journal = "Vaccines",

issn = "2076-393X",

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Bissa, M, Galli, V, Schifanella, L, Vaccari, M, Rahman, MA, Gorini, G, Binello, N, Sarkis, S, Gutowska, A, Silva de Castro, I, Doster, MN, Moles, R, Ferrari, G, Shen, X, Tomaras, GD, Montefiori, DC, N’guessan, KF, Paquin-Proulx, D, Kozlowski, PA, Venzon, DJ, Choo-Wosoba, H, Breed, MW, Kramer, J & Franchini, G 2023, 'In Vivo Treatment with Insulin-like Growth Factor 1 Reduces CCR5 Expression on Vaccine-Induced Activated CD4⁺ T-Cells', Vaccines, vol. 11, no. 11, 1662. https://doi.org/10.3390/vaccines11111662

TY - JOUR

T1 - In Vivo Treatment with Insulin-like Growth Factor 1 Reduces CCR5 Expression on Vaccine-Induced Activated CD4+ T-Cells

AU - Bissa, Massimiliano

AU - Galli, Veronica

AU - Schifanella, Luca

AU - Vaccari, Monica

AU - Rahman, Mohammad Arif

AU - Gorini, Giacomo

AU - Binello, Nicolò

AU - Sarkis, Sarkis

AU - Gutowska, Anna

AU - Silva de Castro, Isabela

AU - Doster, Melvin N.

AU - Moles, Ramona

AU - Ferrari, Guido

AU - Shen, Xiaoying

AU - Tomaras, Georgia D.

AU - Montefiori, David C.

AU - N’guessan, Kombo F.

AU - Paquin-Proulx, Dominic

AU - Kozlowski, Pamela A.

AU - Venzon, David J.

AU - Choo-Wosoba, Hyoyoung

AU - Breed, Matthew W.

AU - Kramer, Joshua

AU - Franchini, Genoveffa

PY - 2023/11

Y1 - 2023/11

N2 - 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).

AB - 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).

KW - CCR5

KW - CD4

KW - HIV

KW - IGF-1

KW - insulin-like growth factor

KW - SIV

KW - T-cells

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U2 - 10.3390/vaccines11111662

DO - 10.3390/vaccines11111662

M3 - Article

AN - SCOPUS:85178267922

SN - 2076-393X

VL - 11

JO - Vaccines

JF - Vaccines

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