PhD candidate North Carolina State University Raleigh, North Carolina, United States
Disclosure(s):
Sangmi Jeong, MA: No financial relationships to disclose
Introduction/Rationale: 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.
