Myeloid Cell Crosstalk Regulates the Efficacy of the DNA/ALVAC/gp120 HIV Vaccine Candidate

Monica Vaccari; Slim Fourati; Dallas R. Brown; Isabela Silva De Castro; Massimiliano Bissa; Luca Schifanella; Melvin N. Doster; Kathryn E. Foulds; Mario Roederer; Richard A. Koup; Yongjun Sui; Jay A. Berzofsky; Rafick Pierre Sekaly; Genoveffa Franchini

doi:10.3389/fimmu.2019.01072

Myeloid Cell Crosstalk Regulates the Efficacy of the DNA/ALVAC/gp120 HIV Vaccine Candidate

Monica Vaccari, Slim Fourati, Dallas R. Brown, Isabela Silva De Castro, Massimiliano Bissa, Luca Schifanella, Melvin N. Doster, Kathryn E. Foulds, Mario Roederer, Richard A. Koup, Yongjun Sui, Jay A. Berzofsky, Rafick Pierre Sekaly, Genoveffa Franchini^*

^*Corresponding author for this work

Medicine, Allergy Division

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

15 Scopus citations

Abstract

Vaccination with DNA-SIV + ALVAC-SIV + gp120 alum results in inflammasome activation, high levels of IL-1β production, emergency myelopoiesis, and the egress of CXCR4+ CD14⁺ pre-monocytes from bone marrow. Previously we have shown that this vaccine-induced innate monocyte memory is associated with decreased risk of SIVmac251 acquisition. Because IL-1β also promotes the propagation of monocyte-derived suppressor (M-MDSC)-like cells, here we extended our analysis to this negative regulator subset, characterizing its levels and functions in macaques. Interestingly, we found that DNA prime engages M-MDSC-like cells and their levels are positively associated with the frequency of CD14+ classical monocytes, and negatively with the levels of CD16⁺ monocytes, correlates of decreased and increased risk of SIV acquisition, respectively. Accordingly, M-MDSC frequency, arginase activity, and NO were all associated with decrease of CD8 T cells responses and worse vaccination outcome. DNA vaccination thus induces innate immunity by engaging three subsets of myeloid cells, M-MDSCs, CD14+ innate monocyte memory, and CD16⁺ monocytes all playing different role in protection. The full characterization of the immunological space created by myeloid cell crosstalk will likely provide clues to improve the efficacy of HIV vaccine candidates.

Original language	English (US)
Article number	1072
Journal	Frontiers in immunology
Volume	10
Issue number	MAY
DOIs	https://doi.org/10.3389/fimmu.2019.01072
State	Published - 2019

Funding

This work was mostly supported with federal funds from the intramural program of the National Cancer Institute, National Institutes of Health, including Contract No. HHSN261200800001E. Contributions were made by the extramural NIAID program (HHSN27201100016C), the Henry M. Jackson Foundation, the US Department of Defense, and the Collaboration for Aids Vaccine Discovery (CAVD) grants OPP1032325, OPP1032817, and OPP1147555 from the Bill and Melinda Gates Foundation. HHSN261200800001E. Contributions were made by the extramural NIAID program (HHSN27201100016C), the Henry M. Jackson Foundation, the US Department of Defense, and the Collaboration for Aids Vaccine Discovery (CAVD) grants OPP1032325, OPP1032817, and OPP1147555 from the Bill and Melinda Gates Foundation. This work was mostly supported with federal funds from the intramural program of the National Cancer Institute, National Institutes of Health, including Contract No.

Keywords

HIV/SIV
MDSC
Myeloid cells
Trained immunity
Vaccine

ASJC Scopus subject areas

Immunology and Allergy
Immunology

UN SDGs

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

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10.3389/fimmu.2019.01072

Cite this

Vaccari, M., Fourati, S., Brown, D. R., De Castro, I. S., Bissa, M., Schifanella, L., Doster, M. N., Foulds, K. E., Roederer, M., Koup, R. A., Sui, Y., Berzofsky, J. A., Sekaly, R. P., & Franchini, G. (2019). Myeloid Cell Crosstalk Regulates the Efficacy of the DNA/ALVAC/gp120 HIV Vaccine Candidate. Frontiers in immunology, 10(MAY), Article 1072. https://doi.org/10.3389/fimmu.2019.01072

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title = "Myeloid Cell Crosstalk Regulates the Efficacy of the DNA/ALVAC/gp120 HIV Vaccine Candidate",

abstract = "Vaccination with DNA-SIV + ALVAC-SIV + gp120 alum results in inflammasome activation, high levels of IL-1β production, emergency myelopoiesis, and the egress of CXCR4+ CD14+ pre-monocytes from bone marrow. Previously we have shown that this vaccine-induced innate monocyte memory is associated with decreased risk of SIVmac251 acquisition. Because IL-1β also promotes the propagation of monocyte-derived suppressor (M-MDSC)-like cells, here we extended our analysis to this negative regulator subset, characterizing its levels and functions in macaques. Interestingly, we found that DNA prime engages M-MDSC-like cells and their levels are positively associated with the frequency of CD14+ classical monocytes, and negatively with the levels of CD16+ monocytes, correlates of decreased and increased risk of SIV acquisition, respectively. Accordingly, M-MDSC frequency, arginase activity, and NO were all associated with decrease of CD8 T cells responses and worse vaccination outcome. DNA vaccination thus induces innate immunity by engaging three subsets of myeloid cells, M-MDSCs, CD14+ innate monocyte memory, and CD16+ monocytes all playing different role in protection. The full characterization of the immunological space created by myeloid cell crosstalk will likely provide clues to improve the efficacy of HIV vaccine candidates.",

keywords = "HIV/SIV, MDSC, Myeloid cells, Trained immunity, Vaccine",

author = "Monica Vaccari and Slim Fourati and Brown, {Dallas R.} and {De Castro}, {Isabela Silva} and Massimiliano Bissa and Luca Schifanella and Doster, {Melvin N.} and Foulds, {Kathryn E.} and Mario Roederer and Koup, {Richard A.} and Yongjun Sui and Berzofsky, {Jay A.} and Sekaly, {Rafick Pierre} and Genoveffa Franchini",

note = "Publisher Copyright: Copyright {\textcopyright} 2019 Vaccari, Fourati, Brown, Silva de Castro, Bissa, Schifanella, Doster, Foulds, Roederer, Koup, Sui, Berzofsky, Sekaly and Franchini. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.",

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T1 - Myeloid Cell Crosstalk Regulates the Efficacy of the DNA/ALVAC/gp120 HIV Vaccine Candidate

AU - Vaccari, Monica

AU - Fourati, Slim

AU - Brown, Dallas R.

AU - De Castro, Isabela Silva

AU - Bissa, Massimiliano

AU - Schifanella, Luca

AU - Doster, Melvin N.

AU - Foulds, Kathryn E.

AU - Roederer, Mario

AU - Koup, Richard A.

AU - Sui, Yongjun

AU - Berzofsky, Jay A.

AU - Sekaly, Rafick Pierre

AU - Franchini, Genoveffa

N1 - Publisher Copyright: Copyright © 2019 Vaccari, Fourati, Brown, Silva de Castro, Bissa, Schifanella, Doster, Foulds, Roederer, Koup, Sui, Berzofsky, Sekaly and Franchini. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

PY - 2019

Y1 - 2019

N2 - Vaccination with DNA-SIV + ALVAC-SIV + gp120 alum results in inflammasome activation, high levels of IL-1β production, emergency myelopoiesis, and the egress of CXCR4+ CD14+ pre-monocytes from bone marrow. Previously we have shown that this vaccine-induced innate monocyte memory is associated with decreased risk of SIVmac251 acquisition. Because IL-1β also promotes the propagation of monocyte-derived suppressor (M-MDSC)-like cells, here we extended our analysis to this negative regulator subset, characterizing its levels and functions in macaques. Interestingly, we found that DNA prime engages M-MDSC-like cells and their levels are positively associated with the frequency of CD14+ classical monocytes, and negatively with the levels of CD16+ monocytes, correlates of decreased and increased risk of SIV acquisition, respectively. Accordingly, M-MDSC frequency, arginase activity, and NO were all associated with decrease of CD8 T cells responses and worse vaccination outcome. DNA vaccination thus induces innate immunity by engaging three subsets of myeloid cells, M-MDSCs, CD14+ innate monocyte memory, and CD16+ monocytes all playing different role in protection. The full characterization of the immunological space created by myeloid cell crosstalk will likely provide clues to improve the efficacy of HIV vaccine candidates.

AB - Vaccination with DNA-SIV + ALVAC-SIV + gp120 alum results in inflammasome activation, high levels of IL-1β production, emergency myelopoiesis, and the egress of CXCR4+ CD14+ pre-monocytes from bone marrow. Previously we have shown that this vaccine-induced innate monocyte memory is associated with decreased risk of SIVmac251 acquisition. Because IL-1β also promotes the propagation of monocyte-derived suppressor (M-MDSC)-like cells, here we extended our analysis to this negative regulator subset, characterizing its levels and functions in macaques. Interestingly, we found that DNA prime engages M-MDSC-like cells and their levels are positively associated with the frequency of CD14+ classical monocytes, and negatively with the levels of CD16+ monocytes, correlates of decreased and increased risk of SIV acquisition, respectively. Accordingly, M-MDSC frequency, arginase activity, and NO were all associated with decrease of CD8 T cells responses and worse vaccination outcome. DNA vaccination thus induces innate immunity by engaging three subsets of myeloid cells, M-MDSCs, CD14+ innate monocyte memory, and CD16+ monocytes all playing different role in protection. The full characterization of the immunological space created by myeloid cell crosstalk will likely provide clues to improve the efficacy of HIV vaccine candidates.

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KW - Trained immunity

KW - Vaccine

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Myeloid Cell Crosstalk Regulates the Efficacy of the DNA/ALVAC/gp120 HIV Vaccine Candidate

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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