Exploring gut host—microbiome interactions associated with RhCMV/SIV vaccine efficacy against SIV in rhesus macaques 2257552

Abstract

Abstract Introduction A live-attenuated rhesus cytomegalovirus (RhCMV)-based vaccine protects ∼59% of rhesus macaques (RM) against simian immunodeficiency virus (SIV) via CD8+ T cell—mediated control, but the exact mechanism of non-protection in ∼41% remain unclear. We previously identified gut microbial features linked to RhCMV/SIV vaccine protection and now aim to validate these signatures and investigate host—microbiome interactions influencing vaccine efficacy. Methods A new cohort of 14 RMs was vaccinated with prime and boost doses of 68-1 RhCMV/SIV vector. At week 79, they were challenged with SIVmac239, and 8 of 14 (57%) were protected. Full-length 16S rRNA and total RNA sequencing were performed on rectal swabs collected at three time points before and after vaccination. Gut microbiome was profiled using full-length 16S sequencing, while gut microbial meta-transcriptome was identified by total RNA-sequencing. Total RNA-seq reads mapped to the RM genome also characterized host immune responses in the gut. Multi-omics data have been processed, and downstream analyses are ongoing. Results From the total RNA-seq data we obtained ∼60 million reads per sample. In our preliminary findings, both 16S and total RNA-seq data contained a high proportion of reads assigned to unknown species, as well as a substantial fraction of unmapped reads. These phenomena present challenges for analyzing host and microbial composition and function in the RM model. Conclusion We will continue to develop the multi-omics analysis pipeline to achieve our aims and present the results at the presentation. The findings will contribute to the optimization of future RhCMV-based vaccine strategies by improving protection prediction and guiding vaccine adjuvants. Funding Source NIAID, NIH, HHS R21AI120713 and Contract No. HHSN272201800008C Topic Categories Mucosal and Regional Immunology (MUC)