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 -
