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Displaying record number 62860

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HXB2 Location	gp160(383-391) gp120(383-391) DNA(7371..7397)	gp160 Epitope Map
Author Location	Env( JR-CSF)
Epitope	FYCNSTQLF	Epitope Alignment
		Show epitope variants
Epitope Name	FF9
Subtype	B
Species (MHC/HLA)	humanized mouse(A*24)
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, 6/8 BLT humanized mice with donor tissue expressing HLA-I alleles A2402/A3002 displayed evolution of A*24-restricted epitope Env FF9. Within a single mouse, the frequency of an individual variant was up to 29% while the frequency of HIV-1_JR-CSF FF9 sequence FYCNSTQLF was 68-89% in these 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.

Displaying record number 56964

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HXB2 Location	gp160(383-391) gp120(383-391) DNA(7371..7397)	gp160 Epitope Map
Author Location	Env
Epitope	FYCNSTQLF	Epitope Alignment
Subtype	CRF01_AE
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Country	Sweden
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	subtype comparisons, computational epitope prediction, vaccine antigen design

Notes

• From HIV-1 sequences of multiple subtypes, bioinformatic prediction generated 174 CTL epitopes from Gag, Pol, Nef, Env and Tat restricted by HLA supertypes A1, A2, A3, A24, B7, B44 and B58; 10 previously-published A2- and B58-restricted epitopes were also included. Of these 184 epitopes, 113 were recognized experimentally in serum from 31 HIV+ patients.
• While Gag, Pol, Env and Nef were highly immunogenic, only 38% of Tat epitopes elicited a response.
• FYCNSTQLF was a predicted epitope restricted by A24 supertype. 1/31 patient(s) responded to it; the patient was not known to carry an allele of A24 supertype. Responding patients were infected with HIV clade(s) CRF01_AE.

References

Perez2008 Carina L. Pérez, Mette V. Larsen, Rasmus Gustafsson, Melissa M. Norström, Ann Atlas, Douglas F. Nixon, Morten Nielsen, Ole Lund, and Annika C. Karlsson. Broadly Immunogenic HLA Class I Supertype-Restricted Elite CTL Epitopes Recognized in a Diverse Population Infected with Different HIV-1 Subtypes. J. Immunol., 180(7):5092-5100, 1 Apr 2008. PubMed ID: 18354235. Show all entries for this paper.