Journal
COMMUNICATIONS BIOLOGY
Volume 5, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s42003-022-04344-2
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Funding
- National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services [HHSN272201800008C, HHSN272201600027C]
- National Institutes of Health, Office of the Director [P51OD010425]
- University of Washington / Fred Hutch Center for AIDS Research, an NIH [AI027757]
- NIAID
- NCI
- NIMH
- NIDA
- NICHD
- NHLBI
- NIA
- NIGMS
- NIDDK
- National Institute of Allergy and Infectious Diseases (NIAID) [P01 AI094417, U19AI128741, UM1 AI124377]
- Oregon National Primate Research Center Core from the National Institutes of Health, Office of the Director [P51OD011092]
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RhCMV-based vaccination against SIV in rhesus macaques can effectively control SIV infection in approximately 55% of vaccinated monkeys by eliciting MHC-E-restricted CD8+ T cells. Analysis of the Mamu-E genomic sequences in rhesus macaques reveals gene duplication and different allele groups that are associated with the lack of vaccine protection.
Rhesus cytomegalovirus (RhCMV)-based vaccination against Simian Immunodeficiency virus (SIV) elicits MHC-E-restricted CD8+ T cells that stringently control SIV infection in similar to 55% of vaccinated rhesus macaques (RM). However, it is unclear how accurately the RM model reflects HLA-E immunobiology in humans. Using long-read sequencing, we identified 16 Mamu-E isoforms and all Mamu-E splicing junctions were detected among HLA-E isoforms in humans. We also obtained the complete Mamu-E genomic sequences covering the full coding regions of 59 RM from a RhCMV/SIV vaccine study. The Mamu-E gene was duplicated in 32 (54%) of 59 RM. Among four groups of Mamu-E alleles: three similar to 5% divergent full-length allele groups (G1, G2, G2_LTR) and a fourth monomorphic group (G3) with a deletion encompassing the canonical Mamu-E exon 6, the presence of G2_LTR alleles was significantly (p = 0.02) associated with the lack of RhCMV/SIV vaccine protection. These genomic resources will facilitate additional MHC-E targeted translational research.
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