Search CTL/CD8+ T-Cell Epitope Database

Found 12 matching records:

Displaying record number 62861

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HXB2 Location	Gag(103-112) p17(103-112) DNA(1096..1125)	Gag Epitope Map
Author Location	Gag( JR-CSF)
Epitope	`KIEEEQTKSM`	Epitope Alignment
		Show epitope variants
Epitope Name	KK10
Subtype	B
Species (MHC/HLA)	humanized mouse
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

Vaccine type	virus, PLG microparticle, recombinant protein
Vaccine strain	B clade
Vaccine component	Gag, virus

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, 9/17 BLT humanized mice with donor tissue expressing HLA-I alleles A0301/A2301 displayed evolution of epitope Gag KK10, known to bind to A*11. Within a single mouse, the frequency of an individual variant was up to 36% while the frequency of HIV-1_JR-CSF KK10 sequence KIEEEQTKSM was 45-93% in these 9 mice. Both HLA-I alleles A*11 and A0301 are categorized into HLA supertype A3 [Sydney, et al. BMC Immunol, 9(1). PMID: 18211710].

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 62858

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HXB2 Location	Gag(119-128) p17(119-128) DNA(1144..1173)	Gag Epitope Map
Author Location	Gag( JR-CSF)
Epitope	`AADTGNSSQV`	Epitope Alignment
		Show epitope variants
Epitope Name	AV10
Subtype	B
Species (MHC/HLA)	humanized mouse
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

Vaccine type	virus, PLG microparticle, recombinant protein
Vaccine strain	B clade
Vaccine component	Gag, virus

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, 8/8 BLT humanized mice with donor tissue expressing HLA-I alleles C0501/C0501 displayed evolution of epitope Gag AV10 which likely binds to C*05. Within a single mouse, the frequency of an individual variant was up to 77% while the frequency of HIV-1_JR-CSF AV10 sequence AADTGNSSQV was <5% in 5/8 mice and 80-98% in the other 3 mice.

References

Displaying record number 62762

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HXB2 Location	Vif(31-39) DNA(5131..5157)	Vif Epitope Map
Author Location	Vif( JR-CSF)
Epitope	`ISGKAKGWI`	Epitope Alignment
		Show epitope variants
Epitope Name	IF9
Subtype	B
Species (MHC/HLA)	humanized mouse(B*18)
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

Vaccine type	virus, PLG microparticle, recombinant protein
Vaccine strain	B clade
Vaccine component	Gag, virus

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, 8/8 BLT humanized mice with donor tissue expressing HLA-I alleles B1801/B4402 displayed evolution of B*18-restricted epitope Vif IF9. Within a single mouse, the frequency of an individual variant was up to 68% while the frequency of HIV-1_JR-CSF IF9 sequence ISGKAKGWI was <5% in 5/8 mice and 17-21% in the other 3 mice.

References

Displaying record number 62862

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HXB2 Location	Vif(31-39) DNA(5131..5157)	Vif Epitope Map
Author Location	Vif( JR-CSF)
Epitope	`ISGKAKGWI`	Epitope Alignment
		Show epitope variants
Epitope Name	IF9
Subtype	B
Species (MHC/HLA)	humanized mouse
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

Vaccine type	virus, PLG microparticle, recombinant protein
Vaccine strain	B clade
Vaccine component	Gag, virus

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, 12/17 BLT humanized mice with donor tissue expressing HLA-I alleles B0702/B5801 displayed evolution of epitope VIF IF9, known to bind to B*57. Within a single mouse, the frequency of an individual variant was up to 97% while the frequency of HIV-1_JR-CSF IF9 sequence ISGKAKGWI was <5% in 2/12 mice and 12-89% in the other 10 mice. B*57 HLA-I alleles and B5801 are categorized into HLA supertype B58 [Sydney, et al. BMC Immunol, 9(1). PMID: 18211710].

References

Displaying record number 62763

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HXB2 Location	Rev(55-63) DNA(8465..8491)	Rev Epitope Map
Author Location	Rev( JR-CSF)
Epitope	`ISERILSTY`	Epitope Alignment
		Show epitope variants
Epitope Name	IY9
Subtype	B
Species (MHC/HLA)	humanized mouse
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

Vaccine type	virus, PLG microparticle, recombinant protein
Vaccine strain	B clade
Vaccine component	Gag, virus

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 A2402/A3002 displayed evolution of epitope Rev IY9, known to bind A*01. Within a single mouse, the frequency of an individual variant was up to 76% while the frequency of HIV-1_JR-CSF IY9 sequence ISERILSTY was <5% in 3/7 mice and 7-53% in the other 4 mice. Both HLA-I alleles A*01 and A3002 are categorized into HLA supertype A1 [Sydney, et al. BMC Immunol, 9(1). PMID: 18211710].

References

Displaying record number 62863

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HXB2 Location	Vpu(14-23) DNA(6101..6130)	Vpu Epitope Map
Author Location	Vpu( JR-CSF)
Epitope	`VAGIIAIIVW`	Epitope Alignment
		Show epitope variants
Epitope Name	VW10
Subtype	B
Species (MHC/HLA)	humanized mouse
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

Vaccine type	virus, PLG microparticle, recombinant protein
Vaccine strain	B clade
Vaccine component	Gag, virus

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, 11/17 BLT humanized mice with donor tissue expressing HLA-I alleles B0702/B5801 displayed evolution of epitope Vpu VW10, predicted to bind to B*57. Within a single mouse, the frequency of an individual variant was up to 76% while the frequency of HIV-1_JR-CSF VW10 sequence VAGIIAIIVW was 17-78% in these 11 mice. B*57 HLA-I alleles and B5801 are categorized into HLA supertype B58 [Sydney, et al. BMC Immunol, 9(1). PMID: 18211710].

References

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

Vaccine type	virus, PLG microparticle, recombinant protein
Vaccine strain	B clade
Vaccine component	Gag, virus

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

Displaying record number 62864

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HXB2 Location	gp160(117-126) gp120(117-126) DNA(6573..6602)	gp160 Epitope Map
Author Location	Env( JR-CSF)
Epitope	`KPCVKLTPLC`	Epitope Alignment
		Show epitope variants
Epitope Name	KC10
Subtype	B
Species (MHC/HLA)	humanized mouse(B*07)
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

Vaccine type	virus, PLG microparticle, recombinant protein
Vaccine strain	B clade
Vaccine component	Gag, virus

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, 5/17 BLT humanized mice with donor tissue expressing HLA-I alleles B0702/B5801 displayed evolution of B*07-restricted epitope Env KC10. Within a single mouse, the frequency of the only observed variant, KPCVqLTPLC, was 17-81% while the frequency of HIV-1_JR-CSF Env KC10 sequence KPCVKLTPLC was 17-83% in these 5 mice.

References

Displaying record number 62865

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HXB2 Location	gp160(205-213) gp120(205-213) DNA(6837..6863)	gp160 Epitope Map
Author Location	Env( JR-CSF)
Epitope	`CPKVSFEPI`	Epitope Alignment
		Show epitope variants
Epitope Name	CI9
Subtype	B
Species (MHC/HLA)	humanized mouse(B*07:02)
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

Vaccine type	virus, PLG microparticle, recombinant protein
Vaccine strain	B clade
Vaccine component	Gag, virus

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, 9/17 BLT humanized mice with donor tissue expressing HLA-I alleles B0702/B5801 displayed evolution of B*07:02-restricted epitope Env CI9. Within a single mouse, the frequency of an individual variant was up to 83% while the frequency of HIV-1_JR-CSF CI9 sequence CPKVSFEPI was 16-94% in these 9 mice.

References

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

Vaccine type	virus, PLG microparticle, recombinant protein
Vaccine strain	B clade
Vaccine component	Gag, virus

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

Displaying record number 62866

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HXB2 Location	gp160(786-794) gp41(275-283) DNA(8580..8606)	gp160 Epitope Map
Author Location	Env( JR-CSF)
Epitope	`GRRGWEILK`	Epitope Alignment
		Show epitope variants
Epitope Name	GK9
Subtype	B
Species (MHC/HLA)	humanized mouse
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

Vaccine type	virus, PLG microparticle, recombinant protein
Vaccine strain	B clade
Vaccine component	Gag, virus

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, 14/17 BLT humanized mice with donor tissue expressing HLA-I alleles B0702/B5801 displayed evolution of epitope Env GK9, known to bind to B*57. Within a single mouse, the frequency of an individual variant was up to 78% while the frequency of HIV-1_JR-CSF GK9 sequence GRRGWEILK was <5% in 12/14 mice and 13-21% in the other 2 mice. B*57 HLA-I alleles and B5801 are categorized into HLA supertype B58 [Sydney, et al. BMC Immunol, 9(1). PMID: 18211710].

References

Displaying record number 62867

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HXB2 Location	Nef(82-90) DNA(9040..9066)	Nef Epitope Map
Author Location	Nef( JR-CSF)
Epitope	`KAAIDLSHF`	Epitope Alignment
		Show epitope variants
Epitope Name	KF9
Subtype	B
Species (MHC/HLA)	humanized mouse(B*58:01)
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

Vaccine type	virus, PLG microparticle, recombinant protein
Vaccine strain	B clade
Vaccine component	Gag, virus

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, 13/17 BLT humanized mice with donor tissue expressing HLA-I alleles B0702/B5801 displayed evolution of B*5801-restricted epitope Nef KF9. Within a single mouse, the frequency of an individual variant was up to 100% while the frequency of HIV-1_JR-CSF CI9 sequence KAAIDLSHF was <5% in 8/13 and 8-88% in the other 5 mice.