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Functional genomic analysis of the 68-1 RhCMV-Mycobacteria tuberculosis vaccine reveals an IL-15 response signature that is conserved with vector attenuation

ABSTRACT: Functional genomic analysis of the 68-1 RhCMV-Mycobacteria tuberculosis vaccine reveals an IL-15 response signature that is conserved with vector attenuation

PROVIDER: PRJNA1143901 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR30123300_1.fastq.gz	Fastqsanger.gz
	SRR30123300_2.fastq.gz	Fastqsanger.gz
	SRR30123400_1.fastq.gz	Fastqsanger.gz
	SRR30123400_2.fastq.gz	Fastqsanger.gz
	SRR30123500_1.fastq.gz	Fastqsanger.gz

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Functional genomic analysis of the 68-1 RhCMV-Mycobacteria tuberculosis vaccine reveals an IL-15 response signature that is conserved with vector attenuation

Project description:Here we conducted a bulk RNA-seq analysis of whole blood samples collected from RMs administered with RhCMV vector vaccines using a prime-boost strategy. Two vaccines were used in this study, including 68-1 RhCMV/TB-6Ag (encoding 6 Mtb protein immunogens) and its attenuated variant, 68-1 RhCMV/Δpp71-TB-6Ag (a cell to cell spread-deficient vaccine vector lacking the Rh110 gene encoding the pp71 tegument protein).

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Nontuberculous mycobacteria

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Pseudomonas veronii strain:68 | isolate:68

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Project description:We investigated the effects of rhesus CMV (RhCMV) on composition and function of the immune system in young macaques. Within months of infection, RhCMV was associated with impressive changes in antigen presenting cells, T cells, and NK cells—and marked expansion of innate-memory CD8+ T cells. These cells express high levels of NKG2A/C and the IL-2- and IL-15-receptor beta chain, CD122. IL-15 was sufficient to drive differentiation of the cells in vitro and in vivo. Expanded NKG2A/C+CD122+CD8+ T cells in RhCMV-infected macaques, but not their NKG2-negative counterparts, were endowed with cytotoxicity against class I-deficient K562 targets and prompt IFN-ɣ production in response to stimulation with IL-12 and IL-18. Because RhCMV clone 68-1 forms the viral backbone of RhCMV-vectored SIV vaccines, we also investigated immune changes following administration of RhCMV 68-1-vectored SIV vaccines. These vaccines led to impressive expansion of NKG2A/C+CD8+ T cells with capacity to inhibit SIV replication ex vivo. Thus, CMV infection and CMV-vectored vaccination drive expansion of functional innate-like CD8 cells via host IL-15 production, suggesting that innate-memory expansion could be achieved by other vaccine platforms expressing IL-15.

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nontuberculosis mycobacteria

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