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Simian immunodeficiency virus strain:SIVmac251

ABSTRACT: SIVmac251 in vaccinated and naive cynomolgus macaques.

PROVIDER: PRJNA528275 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8761830_1.fastq.gz	Fastqsanger.gz
	SRR8761830_2.fastq.gz	Fastqsanger.gz
	SRR8761840_1.fastq.gz	Fastqsanger.gz
	SRR8761840_2.fastq.gz	Fastqsanger.gz
	SRR8761850_1.fastq.gz	Fastqsanger.gz

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Innate protection against intrarectal SIV acquisition by a live Simian-Human immunodeficiency virus vaccine

Project description:Identifying immune correlates of protection is a major challenge in AIDS vaccine development. Anti-Envelope antibodies have been considered critical against SIV/HIV acquisition. Here, we evaluated the efficacy of a SHIV vaccine against SIVmac251 challenge, where the role of antibody was excluded as there was no cross-reactivity between SIV and SHIV Envelope antibodies. After eight low-dose rectal challenges with SIVmac251, 12 SHIV-vaccinated animals demonstrated 83% efficacy, compared to six naïve controls, suggesting protection could be achieved in the absence of anti-Envelope antibodies. Interestingly, CD8+ T cells (and some NK cells) were not essential for the preventing viral acquisition, as none of the CD8-depleted macaques were infected by SIVmac251 challenges. Initial investigation of protective innate immunity revealed that protected animals had elevated pathways related to platelet aggregation/activation, and reduced pathways related to interferon and responses to virus. Moreover, higher expression of platelet factor 4 (PF4) on circulating platelet-leukocyte aggregates was associated with reduced viral acquisition. Our data highlighted the importance of innate immunity and may provide new opportunities for novel HIV vaccines or therapeutic strategy development.

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Transcription profiling by high throughput sequencing of rhesus macaques vaccinated with two regimens to define correlates of protection against repeated low dose simian immunodeficiency virus challenges

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Simian immunodeficiency virus strain:SIVmac251

Project description:Simian immunodeficiency virus strain:SIVmac251 Raw sequence reads

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Expression data from rhesus macaque blood CD8+ T cells

Project description:Immunization of macaques with simian immunodeficiency virus with deletions in nef (SIV?nef) has been shown to elicit protective immunity to infection by pathogenic SIV, yet our understanding of the mechanisms that orchestrate protection and prevent pathogenesis remains limited. In the study, we utilize whole-genome transcriptional profiling to reveal molecular signatures of protective immunity in circulating CD8+ T cells of rhesus macaques vaccinated with SIVmac239?nef and challenged with pathogenic SIVmac251. Microarrays were used to characterize changes in gene expression in blood CD8+ T cells that occur following vaccination of rhesus macaques with attenuated SIV?nef and subsequent challenge with pathogenic SIVmac251, in comparison to corresponding changes in healthy controls and unvaccinated animals infected with pathogenic SIVmac251 CD8+ T cells were isolated by magnetic beads from the blood of healthy uninfected macaques, macaques vaccinated with SIV?nef, and unvaccinated controls infected with SIVmac251, and used for RNA extraction and hybridization on Affymetrix microarrays. Blood samples from vaccinated animals were collected prior to vaccination, at 3, 20, and 40 weeks following vaccination. After the 40 week vaccination period, macaques were challenged with SIVmac251, and blood was again collected at 3 weeks following challenge. Blood was collected from the unvaccinated controls at 3 weeks following infection with SIVmac251

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Passive Transfer of Vaccine-Elicited Antibodies Protects Against SIV in Rhesus Macaques

Project description:In this study, we show that passive transfer of purified antibodies from vaccinated macaques can protect naïve animals against SIVmac251 challenges. The protective signature included multiple antibody functions and correlated with upregulation of interferon pathways in the vaccinated animals. Adoptive transfer of purified IgG from the vaccinated animals with the most robust protective signatures provided partial protection against SIVmac251 challenges in naïve recipient rhesus macaques. These data demonstrate the protective efficacy of purified vaccine-elicited antiviral antibodies, even in the absence of virus neutralization.

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