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Myeloid cells are transcriptionally distinct between RhCMV/SIV vaccinated rhesus macaques protected from SIV and unvaccinated SIV-infected animals.

ABSTRACT: Myeloid cells are transcriptionally distinct between RhCMV/SIV vaccinated rhesus macaques protected from SIV and unvaccinated SIV-infected animals.

PROVIDER: PRJNA1235144 | ENA |

REPOSITORIES: ENA

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Myeloid cells are transcriptionally distinct between RhCMV/SIV vaccinated rhesus macaques protected from SIV and unvaccinated SIV-infected animals.

Project description:The 68-1 rhesus cytomegalovirus (RhCMV) vector which expresses Simian Immunodeficiency Virus (SIV) genes (Gag/Tat/Nef/5-Pol) is effective in controlling and clearing SIV in rhesus macaques and the human ortholog vector is a vaccine candidate for the prevention of HIV. Currently the RhCMV/SIV vaccine is only effective in ~55% (referred to as protected animals) of Rhesus Macaques. A previous study by Barrenäs et al., 2021, showed that significant gene expression changes in a key set of IL-15 linked genes was correlated with a protection outcome. To further our understanding of the transcriptomic state if cells in protected animals and mechanisms of protection induced by the RhCMV vaccine we performed single cell RNA-sequencing on PBMCs from protected, non-protected and unvaccinated animals at longitudinal time points post SIV challenge. We identified monocytes, CD8 T cells and NK cells were primarily responsible for expression of genes in the IL-15 enriched protective signature. Myeloid cells were transcriptionally distinct 1) from all other cell types, 2) between nonprotected and protected vaccinated RMs and 3) between protected and unvaccinated SIV-infected animals. Specifically, transcriptomics indicated that myeloid cells were more activated and mature in protected animals by the vaccine at pre-challenge and post-challenge time points. This suggests that the transcriptional state of myeloid cells is essential in eliciting a protection outcome and could be used to determine whether an animal will be protected after vaccination.

2025-08-01 | GSE291725 | GEO

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Comparative genome sequencing of wild type rhesus cytomegalovirus (RhCMV) with a recombinant RhCMV lacking ORF 178

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Challenge of vaccinated and unvaccinated salmon with Aeromonas salmonicida

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Host response to RhCMV/SIV immunization through subcutaneous and oral route

Project description:Host response to RhCMV/SIV immunization through subcutaneous and oral route

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Cytomegalovirus-mediated expansion of IL-15-responsive innate-memory cells with SIV killing function

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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PBMC expression profiles of BCG vaccine protected infants and of BCG vaccinated infants who develop tuberculosis disease

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