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Displaying record number 62859

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HXB2 Location	gp160(30-40) gp120(30-40) DNA(6312..6344)	gp160 Epitope Map
Author Location	Env( JR-CSF)
Epitope	AVEKLWVTVYY	Epitope Alignment
		Show epitope variants
Epitope Name	AY10
Subtype	B
Species (MHC/HLA)	humanized mouse(B*18:01)
Immunogen	HIV-1 infection, vaccine, virus
Experimental methods	Cytokine production, IVAG challenge, Other, T-cell Elispot
Keywords	vaccine-induced immune responses, escape, assay or method development

Vaccine Details

Notes

• This comprehensive longitudinal study is the first to document that clinically-relevant HIV-1-specific T cell responses can be induced by rapid prime (recombinant Gag polyprotein adsorbed to PLGA microspheres) with boost (Gag-expressing HSV-1) immunization in 31 BLT humanized mice, each generated from 1/4 individual donors with distinct human HLA alleles, during the first 12 weeks of HIV-1_JR-CSF infection. Gag-immunized BLT humanized mice were capable of mounting strong and broadly directed HIV-1 specific IFNγ+ T cell responses that drive CTL epitope viral evolution and enhance Gag-specific post-challenge responses while also associating with significant, yet modest, reductions in early HIV-1 viremia.
• No pre-challenge Gag-specific responses were detected and impact on early HIV-1 viremia was only transient. Authors suggest that improvements in immunization strategy and/or additional maturation of recapitulated human immune system may be beneficial for further vaccine studies.
• Origination and increasing frequency of epitope variants were generally observed in individual BLT humanized mice infected with HIV-1_JR-CSF. At 12 weeks post infection, complete or nearly complete escape (<10% of inoculum sequence) was observed in 1 CTL epitope in 11/25 mice, 2 CTL epitopes in 6/25 mice and 3 CTL epitopes in 5/25 mice.
• At 12 weeks post HIV-1_JR-CSF-infection, 7/8 BLT humanized mice with donor tissue expressing HLA-I alleles B1801/B4402 displayed evolution of B*18:01/B*44:02-restricted epitope Env AY10. Within a single mouse, the frequency of an individual variant was up to 67% while the frequency of HIV-1_JR-CSF AY10 sequence AVEKLWVTVYY was <5% in 1/7 mice and 17-93% in the other 6 mice.

References

Claiborne2019 Daniel T. Claiborne, Timothy E. Dudek, Colby R. Maldini, Karen A. Power, Musie Ghebremichael, Edward Seung, Elizabeth F. Mellors, Vladimir D. Vrbanac, Katharine Krupp, Abigail Bisesi, Andrew M. Tager, David M. Knipe, Christian L. Boutwell, and Todd M. Allen. Immunization of BLT Humanized Mice Redirects T Cell Responses to Gag and Reduces Acute HIV-1 Viremia. J. Virol., 93(20), 15 Oct 2019. PubMed ID: 31375576. Show all entries for this paper.