Vaccine-induced temporal cross-talk between myeloid cells reduces the risk of SIVmac251 acquisition

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Abstract Vaccination with recombinant ALVAC + gp120 alum boosts has decreased the risk of acquisition of HIV/SIV in humans and in macaques. We tested whether the substitution of the first ALVAC-SIV immunization with either a DNA- or an Ad26-based SIV vaccine would affect vaccine efficacy. We found that the DNA prime was associated with 52% vaccine efficacy whereas the Ad26 prime regimen was ineffective. The two primes differently altered the monocytes levels of CD14+DR+ classical monocytes and myeloid-derived suppressor cells (MDSC) in blood. The DNA resulted in a more pronounced expansion of CD14+DR+ than the Ad26 prime. In this group the frequency of classical monocytes was associated with higher levels of SIV specific CD4+ T cell responses and delayed SIVmac251 acquisition, whereas MDSC correlated with lower levels of T cell responses and early acquisition. Accordingly, plasma levels of arginase, an enzyme produced by MDSC and linked to the suppression of immune responses, also correlated with early SIVmac251 acquisition. Systems biology studies revealed a correlation between the expression of distinct gene expression signatures associated to monocytes which correlated either with acquisition or protection. Altogether these data indicate that the priming may shape the cross-talk between monocytes and MDSCs and highlights the importance of vaccine induced innate responses in protection from virus acquisition.