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

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

JOURNAL=Frontiers in Immunology

VOLUME=Volume 10 - 2019

YEAR=2019

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.01072

DOI=10.3389/fimmu.2019.01072

ISSN=1664-3224

ABSTRACT=The DNA-SIV + ALVAC-SIV + gp120 alum boost vaccine regimen induces innate monocyte memory immunity via inflammasome activation, high levels of IL-1 production, emergency myelopoiesis, and the egress of CXCR4+CD14+ pre-monocytes from bone marrow. Vaccine-associated innate monocyte memory is itself associated with decreased risk of SIVmac251 acquisition and decreased T-cell activation. Interestingly, this regimen also induced CD16+ monocytes that are instead associated with an increased risk of SIV acquisition. Because IL-1 also promotes the propagation of monocyte-derived suppressor (M-MDSC)-like cells, we extended our analysis here to include them. We found that engagement of M-MDSC-like cells by the DNA prime was associated with the frequency of CD14+ classical monocytes, and with the induction of arginase activity that inversely correlated with functional SIV-specific CD8+ T cells. Furthermore, arginase activity positively correlated with the frequency of CD16+ monocytes and nitric oxide (NO) signaling. Accordingly, M-MDSC frequency, arginase activity, and NO were associated with an increased risk of SIVmac251 acquisition. DNA vaccination thus induces protective immunity by engaging three subsets of myeloid cells, M-MDSCs, CD14+ innate monocyte memory, and CD16+ monocytes. The full characterization of the immunological space created by myeloid cell crosstalk will likely provide clues to improve the efficacy of HIV vaccine candidates.