Dataset Information


Transcriptomic profiling of rhesus macaques vaccinated with Ad26/ALVAC+gp120 or DNA/ALVAC+gp120

ABSTRACT: We contrasted innate and adaptive immune responses of HIV vaccine candidates of varying efficacy in macaques that shared the ALVAC+gp120 protein boost with an ALVAC, DNA or Ad26 prime modality. The vaccine efficacies of the DNA/ALVAC+gp120 and ALVAC/ALVAC+gp120 vaccine regimens, both protective, were associated with qualitative temporal-spatial differences in the innate CD14+ and CD16+ cells in blood and tissues. The activation of hypoxia and the inflammasome in CD14+ DR+ CD16- classical monocytes and CD4+ Th2 responses correlated with a decreased risk of SIVmac251 acquisition. CD4+ Th2 cells, in turn, correlated with mucosal NKp44+ cells and mucosal protective antibodies to V2. In contrast, the Ad26/ALVAC+gp120 vaccine resulted in increased de novo differentiated CX3CR1+ CD163+ macrophages in lymph nodes, increased CD4+ Th17 cells in blood and rectal mucosa, and a lack vaccine efficacy. These data posit that the engagement of classical monocytes and inflammasome activation is central for the elicitation of protective innate and adaptive responses by the ALVAC-based HIV vaccine platform. Overall design: Twenty four (24) rhesus macaques were randomized to two vaccination groups. One group (n=12) was primed once with Ad26 (at week 0) and boosted twice with ALVAC-SIV/gp120 in Alum adjuvant (at week 12 and week 24). The second group (n=12) was primed twice with DNA (at week 0 and week 4) and boosted twice with ALVAC-SIV/gp120 in Alum adjuvant (at week 12 and week 24). Blood samples were taken pre-vaccination, 24 hours after the first boost (week 12), 2 weeks after the first boost (week 14), 24 hours after the second boost (week 24) and 1 week after the second boost (week 15). All the samples were taken before SIV challenge. One animal (R270) who received the Ad26/ALVAC+gp120 vaccine was not included in the transcriptomic study because of a lack of blood samples. Blood samples were conserved in PAXgene tubes. RNA was extracted and hybridized to Illumina beadchips.

INSTRUMENT(S): Illumina HumanHT-12 V4.0 expression beadchip

SUBMITTER: Slim Fourati  

PROVIDER: GSE108011 | GEO | 2018-02-23


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HIV vaccine candidate activation of hypoxia and the inflammasome in CD14<sup>+</sup> monocytes is associated with a decreased risk of SIV<sub>mac251</sub> acquisition.

Vaccari Monica M   Fourati Slim S   Gordon Shari N SN   Brown Dallas R DR   Bissa Massimilano M   Schifanella Luca L   Silva de Castro Isabela I   Doster Melvin N MN   Galli Veronica V   Omsland Maria M   Fujikawa Dai D   Gorini Giacomo G   Liyanage Namal P M NPM   Trinh Hung V HV   McKinnon Katherine M KM   Foulds Kathryn E KE   Keele Brandon F BF   Roederer Mario M   Koup Richard A RA   Shen Xiaoying X   Tomaras Georgia D GD   Wong Marcus P MP   Munoz Karissa J KJ   Gach Johannes S JS   Forthal Donald N DN   Montefiori David C DC   Venzon David J DJ   Felber Barbara K BK   Rosati Margherita M   Pavlakis George N GN   Rao Mangala M   Sekaly Rafick-Pierre RP   Franchini Genoveffa G  

Nature medicine 20180521 6

Qualitative differences in the innate and adaptive responses elicited by different HIV vaccine candidates have not been thoroughly investigated. We tested the ability of the Aventis Pasteur live recombinant canarypox vector (ALVAC)-SIV, DNA-SIV and Ad26-SIV vaccine prime modalities together with two ALVAC-SIV + gp120 protein boosts to reduce the risk of SIV<sub>mac251</sub> acquisition in rhesus macaques. We found that the DNA and ALVAC prime regimens were effective, but the Ad26 prime was not.  ...[more]

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