Project name: Macaca mulatta

Description: Systemic vaccination with the attenuated virus SIVmac239-∆Nef provides sterilizing or partial protection to rhesus monkeys challenged with WT SIV strains, providing important opportunities to study key immunological components of a protective host response. Here we show that intravenous vaccination with SIVmac239-∆Nef provides two potentially crucial immunological barriers localized at mucosal surfaces that correlate with the vaccine’s protective effects against WT SIVmac251 vaginal challenge: 1) a conditioned and coordinated response from the mucosal epithelium that blunts the early inflammatory and chemotactic signalling cascade that aids virus propagation and expansion; 2) early on-site generation/diversification of SIV-specific Abs from ectopic germinal center-like lymphoid aggregates. This unique host response to WT SIVmac251 in the female reproductive tract of SIVmac239-∆Nef-vaccinated animals points to a multi-layered strategy for a protective host response during immunodeficiency virus exposure—rapid induction of humroal immunity at mucosal surfaces without the deleterious inflammatory side effects tied to innate recognition of virus. This vaccine-induced host response highlights potential key protective mechanisms needed for an effective HIV vaccineOverall design: Total RNA was isolated from the cervix of 17 Indian Rhesus macaques (3 uninfected animals; 5 unvaccinated animals 4-5 days post vaginal exposure with SIVmac251; 4 SIVmac239-∆Nef-vaccinated animals before challenge; 5 SIVmac239-∆Nef-vaccinated animals 4-5 days post vaginal exposure with SIVmac251) and prepared for hybridization on Affymetrix GeneChip Rhesus Macaque Genome Arrays. Replicate arrays were performed for a number of the samples to minimize assay noise and significant host genes altered during virus exposure in female reproductive tract tissue were identified by their associated q-values ( 1.2).

Data type: Transcriptome or Gene expression

Sample scope: Multiisolate

Relevance: ModelOrganism

Release date: 2012-05-31

Last updated: 2011-10-26