Project description:Mucosal priming of rhesus macaques with replicating Adenovirus SIV-recombinants and systemic boosting with ALVAC-SIV plus envelope protein or DNA encoding SIV genes plus envelope protein elicited strong immunologic responses in both compartments. Following repeated low-dose intrarectal SIV challenges, significant acquisition delay compared to adjuvant controls was not observed. However, delayed acquisition in both vaccine arms and adjuvant controls compared to naïve controls led to identification of transcriptomic signatures associated with protective innate immunity. Vaccinated females but not males exhibited significantly lower acute viremia compared to same-sex controls, confirming our previously reported sex-difference in SIV vaccine outcomes. The rectal microbiome of females and males responded differently to the prime-boost regimen and differentially associated with viremia control and systemic and mucosal humoral immunity. We conclude that the impact on protective efficacy of vaccine-induced microbiome alteration in males and females and trained immunity are factors of significant importance in vaccine outcome.
Project description:Results from the Step trial in humans and studies in non-human primates highlighted a role for heightened activated CD4 T cell response in promoting HIV/SIV acquisition. However, the contribution of vaccine-specific CD4 T cell response in influencing protection is not known. Here, using the macaque model, we show that vaccine-induced Th1-biased CCR5+ CD4 T cell response in blood and mucosal tissue above a certain thresh¬old is detrimental for vaccine-mediated protection against pathogenic mucosal SIV infections.
Project description:This study describes differential miRNA expression in intact colon tissue during acute SIV infection of rhesus macaques. Nine miRNAs were found to be significantly affected by infection, with 5 down-regulated and 4 up-regulated miRNAs. The expression of one upregulated miRNA was further characterized and found to be significantly elevated specifically in response to SIV replication and not immune activation/inflammation accompanying SIV infection.
Project description:This study describes differential miRNA expression in intact colon tissue during acute SIV infection of rhesus macaques. Nine miRNAs were found to be significantly affected by infection, with 5 down-regulated and 4 up-regulated miRNAs. The expression of one upregulated miRNA was further characterized and found to be significantly elevated specifically in response to SIV replication and not immune activation/inflammation accompanying SIV infection. We performed TaqMan Low Density Array based high throughput miRNA analysis on intact colon tissue from 10 acutely SIV-infected and 5 uninfected control macaques. All SIV-infected animals were inoculated intravenously with 100TCID50 of SIV. Out of the ten, one animal each was at 7, 8 and 10DPI (days post infection), 3 each at 13 and 21DPI, and 1 at 29DPI. microRNA reverse transcription and preamplification was performed according to the manufacturerM-bM-^@M-^Ys recommendation. Data analysis was performed using RQ Manager 1.2.2 and DataAssist v3.01 software. Data was normalized using Global normalization method and multiple comparisons correction was performed using Benjamini-Hochberg method.
Project description:An attenuated Lassa vaccine in SIV-infected rhesus macaques does not persist or cause renavirus disease but does elicit protective immunity
Project description:Splenic tissue was isolated from four adult male Indian-origin Rhesus monkeys serologically positive for non-pathogenic SHIV 89.6 and from matched uninfected four adult male Indian-origin Rhesus monkeys respectively. The corresponding RNA was processed by cDNA microarray analysis. Keywords: SIV infection