Identification of conserved subdominant HIV Type 1 CD8(+) T Cell epitopes restricted within common HLA Supertypes for therapeutic HIV Type 1 vaccines

Ingrid Karlsson; Henrik Kløverpris; Kristoffer Jarlov Jensen; Anette Stryhn Buus; Søren Buus; Annika Karlsson; Lasse Vinner; Philip Goulder; Anders Fomsgaard

doi:10.1089/aid.2012.0081

Identification of conserved subdominant HIV Type 1 CD8(+) T Cell epitopes restricted within common HLA Supertypes for therapeutic HIV Type 1 vaccines

Ingrid Karlsson, Henrik Kløverpris, Kristoffer Jarlov Jensen, Anette Stryhn Buus, Søren Buus, Annika Karlsson, Lasse Vinner, Philip Goulder, Anders Fomsgaard

Department of Immunology and Microbiology

8 Citations (Scopus)

Abstract

The high HIV-1 prevalence, up to 4.6% in Guinea-Bissau, West Africa, makes it a relevant location for testing of therapeutic vaccines. With the aim of performing a clinical study in Guinea-Bissau, after first testing the vaccine for safety in Denmark, Europe, we here describe the design of a universal epitope peptide-based T cell vaccine with relevance for any geographic locations. The two major obstacles when designing such a vaccine are the high diversities of the HIV-1 genome and of the human major histocompatibility complex (MHC) class I. We selected 15 CD8-restricted epitopes predicted from conserved regions of HIV-1 that were subdominant (i.e., infrequently targeted) within natural infections. Moreover, the epitopes were predicted to be restricted to at least one of the five common HLA supertypes (HLA-A01, A02, A03, B07, and B44). Here, we validated the resulting peptide-specific, HLA-restricted T cell specificities using peptide-MHC class I tetramer labeling of CD8(+) T cells from HIV-1-infected individuals. The selected vaccine epitopes are infrequently targeted in HIV-1-infected individuals from both locations. Moreover, we HLA-typed HIV-1-infected individuals and demonstrated that the selected vaccine epitopes, when targeted, are restricted to the five most common HLA supertypes at both locations. Thus, the HLA supertype-directed approach achieved HLA coverage of 95% and 100% of the examined cohorts in Guinea-Bissau and Denmark, respectively. In conclusion, the selected vaccine epitopes match the host populations and HIV-1 strains of these two distant geographic regions, justifying clinical testing in both locations.

Original language	English
Journal	AIDS Research and Human Retroviruses
Volume	28
Issue number	11
Pages (from-to)	1434-1443
Number of pages	10
ISSN	0889-2229
DOIs	https://doi.org/10.1089/aid.2012.0081
Publication status	Published - 1 Nov 2012

Keywords

AIDS Vaccines
Adolescent
Adult
CD8-Positive T-Lymphocytes
Denmark
Drug Evaluation, Preclinical
Epitopes, T-Lymphocyte
Female
Guinea-Bissau
HIV Infections
HIV-1
HLA Antigens
Histocompatibility Testing
Humans
Male
Middle Aged
Molecular Sequence Data
Predictive Value of Tests
Sequence Alignment
Vaccines, DNA

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1089/aid.2012.0081

Cite this

Karlsson, I., Kløverpris, H., Jensen, K. J., Buus, A. S., Buus, S., Karlsson, A., Vinner, L., Goulder, P., & Fomsgaard, A. (2012). Identification of conserved subdominant HIV Type 1 CD8(+) T Cell epitopes restricted within common HLA Supertypes for therapeutic HIV Type 1 vaccines. AIDS Research and Human Retroviruses, 28(11), 1434-1443. https://doi.org/10.1089/aid.2012.0081

Identification of conserved subdominant HIV Type 1 CD8(+) T Cell epitopes restricted within common HLA Supertypes for therapeutic HIV Type 1 vaccines. / Karlsson, Ingrid; Kløverpris, Henrik; Jensen, Kristoffer Jarlov et al.
In: AIDS Research and Human Retroviruses, Vol. 28, No. 11, 01.11.2012, p. 1434-1443.

Research output: Contribution to journal › Journal article › Research › peer-review

Karlsson, I, Kløverpris, H, Jensen, KJ, Buus, AS , Buus, S, Karlsson, A, Vinner, L, Goulder, P & Fomsgaard, A 2012, 'Identification of conserved subdominant HIV Type 1 CD8(+) T Cell epitopes restricted within common HLA Supertypes for therapeutic HIV Type 1 vaccines', AIDS Research and Human Retroviruses, vol. 28, no. 11, pp. 1434-1443. https://doi.org/10.1089/aid.2012.0081

@article{532d6d07ccec4c619c44f00695fb95cb,

title = "Identification of conserved subdominant HIV Type 1 CD8(+) T Cell epitopes restricted within common HLA Supertypes for therapeutic HIV Type 1 vaccines",

abstract = "The high HIV-1 prevalence, up to 4.6% in Guinea-Bissau, West Africa, makes it a relevant location for testing of therapeutic vaccines. With the aim of performing a clinical study in Guinea-Bissau, after first testing the vaccine for safety in Denmark, Europe, we here describe the design of a universal epitope peptide-based T cell vaccine with relevance for any geographic locations. The two major obstacles when designing such a vaccine are the high diversities of the HIV-1 genome and of the human major histocompatibility complex (MHC) class I. We selected 15 CD8-restricted epitopes predicted from conserved regions of HIV-1 that were subdominant (i.e., infrequently targeted) within natural infections. Moreover, the epitopes were predicted to be restricted to at least one of the five common HLA supertypes (HLA-A01, A02, A03, B07, and B44). Here, we validated the resulting peptide-specific, HLA-restricted T cell specificities using peptide-MHC class I tetramer labeling of CD8(+) T cells from HIV-1-infected individuals. The selected vaccine epitopes are infrequently targeted in HIV-1-infected individuals from both locations. Moreover, we HLA-typed HIV-1-infected individuals and demonstrated that the selected vaccine epitopes, when targeted, are restricted to the five most common HLA supertypes at both locations. Thus, the HLA supertype-directed approach achieved HLA coverage of 95% and 100% of the examined cohorts in Guinea-Bissau and Denmark, respectively. In conclusion, the selected vaccine epitopes match the host populations and HIV-1 strains of these two distant geographic regions, justifying clinical testing in both locations.",

keywords = "AIDS Vaccines, Adolescent, Adult, CD8-Positive T-Lymphocytes, Denmark, Drug Evaluation, Preclinical, Epitopes, T-Lymphocyte, Female, Guinea-Bissau, HIV Infections, HIV-1, HLA Antigens, Histocompatibility Testing, Humans, Male, Middle Aged, Molecular Sequence Data, Predictive Value of Tests, Sequence Alignment, Vaccines, DNA",

author = "Ingrid Karlsson and Henrik Kl{\o}verpris and Jensen, {Kristoffer Jarlov} and Buus, {Anette Stryhn} and S{\o}ren Buus and Annika Karlsson and Lasse Vinner and Philip Goulder and Anders Fomsgaard",

year = "2012",

month = nov,

day = "1",

doi = "10.1089/aid.2012.0081",

language = "English",

volume = "28",

pages = "1434--1443",

journal = "AIDS Research and Human Retroviruses",

issn = "0889-2229",

publisher = "Mary AnnLiebert, Inc. Publishers",

number = "11",

}

TY - JOUR

T1 - Identification of conserved subdominant HIV Type 1 CD8(+) T Cell epitopes restricted within common HLA Supertypes for therapeutic HIV Type 1 vaccines

AU - Karlsson, Ingrid

AU - Kløverpris, Henrik

AU - Jensen, Kristoffer Jarlov

AU - Buus, Anette Stryhn

AU - Buus, Søren

AU - Karlsson, Annika

AU - Vinner, Lasse

AU - Goulder, Philip

AU - Fomsgaard, Anders

PY - 2012/11/1

Y1 - 2012/11/1

N2 - The high HIV-1 prevalence, up to 4.6% in Guinea-Bissau, West Africa, makes it a relevant location for testing of therapeutic vaccines. With the aim of performing a clinical study in Guinea-Bissau, after first testing the vaccine for safety in Denmark, Europe, we here describe the design of a universal epitope peptide-based T cell vaccine with relevance for any geographic locations. The two major obstacles when designing such a vaccine are the high diversities of the HIV-1 genome and of the human major histocompatibility complex (MHC) class I. We selected 15 CD8-restricted epitopes predicted from conserved regions of HIV-1 that were subdominant (i.e., infrequently targeted) within natural infections. Moreover, the epitopes were predicted to be restricted to at least one of the five common HLA supertypes (HLA-A01, A02, A03, B07, and B44). Here, we validated the resulting peptide-specific, HLA-restricted T cell specificities using peptide-MHC class I tetramer labeling of CD8(+) T cells from HIV-1-infected individuals. The selected vaccine epitopes are infrequently targeted in HIV-1-infected individuals from both locations. Moreover, we HLA-typed HIV-1-infected individuals and demonstrated that the selected vaccine epitopes, when targeted, are restricted to the five most common HLA supertypes at both locations. Thus, the HLA supertype-directed approach achieved HLA coverage of 95% and 100% of the examined cohorts in Guinea-Bissau and Denmark, respectively. In conclusion, the selected vaccine epitopes match the host populations and HIV-1 strains of these two distant geographic regions, justifying clinical testing in both locations.

AB - The high HIV-1 prevalence, up to 4.6% in Guinea-Bissau, West Africa, makes it a relevant location for testing of therapeutic vaccines. With the aim of performing a clinical study in Guinea-Bissau, after first testing the vaccine for safety in Denmark, Europe, we here describe the design of a universal epitope peptide-based T cell vaccine with relevance for any geographic locations. The two major obstacles when designing such a vaccine are the high diversities of the HIV-1 genome and of the human major histocompatibility complex (MHC) class I. We selected 15 CD8-restricted epitopes predicted from conserved regions of HIV-1 that were subdominant (i.e., infrequently targeted) within natural infections. Moreover, the epitopes were predicted to be restricted to at least one of the five common HLA supertypes (HLA-A01, A02, A03, B07, and B44). Here, we validated the resulting peptide-specific, HLA-restricted T cell specificities using peptide-MHC class I tetramer labeling of CD8(+) T cells from HIV-1-infected individuals. The selected vaccine epitopes are infrequently targeted in HIV-1-infected individuals from both locations. Moreover, we HLA-typed HIV-1-infected individuals and demonstrated that the selected vaccine epitopes, when targeted, are restricted to the five most common HLA supertypes at both locations. Thus, the HLA supertype-directed approach achieved HLA coverage of 95% and 100% of the examined cohorts in Guinea-Bissau and Denmark, respectively. In conclusion, the selected vaccine epitopes match the host populations and HIV-1 strains of these two distant geographic regions, justifying clinical testing in both locations.

KW - AIDS Vaccines

KW - Adolescent

KW - Adult

KW - CD8-Positive T-Lymphocytes

KW - Denmark

KW - Drug Evaluation, Preclinical

KW - Epitopes, T-Lymphocyte

KW - Female

KW - Guinea-Bissau

KW - HIV Infections

KW - HIV-1

KW - HLA Antigens

KW - Histocompatibility Testing

KW - Humans

KW - Male

KW - Middle Aged

KW - Molecular Sequence Data

KW - Predictive Value of Tests

KW - Sequence Alignment

KW - Vaccines, DNA

U2 - 10.1089/aid.2012.0081

DO - 10.1089/aid.2012.0081

M3 - Journal article

C2 - 22747336

SN - 0889-2229

VL - 28

SP - 1434

EP - 1443

JO - AIDS Research and Human Retroviruses

JF - AIDS Research and Human Retroviruses

IS - 11

ER -

Identification of conserved subdominant HIV Type 1 CD8(+) T Cell epitopes restricted within common HLA Supertypes for therapeutic HIV Type 1 vaccines

Abstract

Keywords

UN SDGs

Access to Document

Fingerprint

Cite this