Broadening of the T-cell repertoire to HIV-1 Gag p24 by vaccination of HLA-A2/DR transgenic mice with overlapping peptides in the CAF05 adjuvant

Karen S Korsholm, Ingrid Karlsson, Sheila T Tang, Lea Brandt, Else Marie Agger, Claus Aagaard, Peter Andersen, Anders Fomsgaard

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Induction of broad T-cell immune responses is regarded as critical for vaccines against the human immunodeficiency virus type 1 (HIV-1) which exhibit high diversity and, therefore, focus has been on inducing cytotoxic CD8 T-cell responses against the more conserved parts of the virus, such as the Gag protein. Herein, we have used the p24 protein which contains a range of conserved T-cell epitopes. We demonstrate that a vaccine of HIV-1 subtype B consensus group-specific antigen (Gag) p24 protein with the CD8-inducing liposomal cationic adjuvant formulation (CAF) 05, induces both CD4 and CD8 T-cell responses in CB6F1 mice. The adjuvanted vaccine also induced functional antigen-specific cytotoxicity in vivo. Furthermore, we found that when fragmenting the Gag p24 protein into overlapping Gag p24 peptides, a broader T-cell epitope specificity was induced in the humanized human leukocyte antigen (HLA)-A2/DR-transgenic mouse model. Thus, combining overlapping Gag p24 peptides with CAF05 appears to be a promising and simple strategy for inducing broader T-cell responses to multiple conserved epitopes which will be relevant for both prophylactic and therapeutic HIV-1 vaccines.
OriginalsprogEngelsk
TidsskriftPLOS ONE
Vol/bind8
Udgave nummer5
Sider (fra-til)e63575
ISSN1932-6203
DOI
StatusUdgivet - 2013

Fingeraftryk

T-cells
HLA Antigens
Human immunodeficiency virus 1
Viruses
varespladib methyl
adjuvants
HIV-1
T-lymphocytes
vaccination
genetically modified organisms
peptides
antigens
Antigens
Peptides
mice
Vaccines
vaccines
epitopes
T-Lymphocyte Epitopes
Proteins

Citer dette

Korsholm, Karen S ; Karlsson, Ingrid ; Tang, Sheila T ; Brandt, Lea ; Agger, Else Marie ; Aagaard, Claus ; Andersen, Peter ; Fomsgaard, Anders. / Broadening of the T-cell repertoire to HIV-1 Gag p24 by vaccination of HLA-A2/DR transgenic mice with overlapping peptides in the CAF05 adjuvant. I: PLOS ONE. 2013 ; Bind 8, Nr. 5. s. e63575.
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abstract = "Induction of broad T-cell immune responses is regarded as critical for vaccines against the human immunodeficiency virus type 1 (HIV-1) which exhibit high diversity and, therefore, focus has been on inducing cytotoxic CD8 T-cell responses against the more conserved parts of the virus, such as the Gag protein. Herein, we have used the p24 protein which contains a range of conserved T-cell epitopes. We demonstrate that a vaccine of HIV-1 subtype B consensus group-specific antigen (Gag) p24 protein with the CD8-inducing liposomal cationic adjuvant formulation (CAF) 05, induces both CD4 and CD8 T-cell responses in CB6F1 mice. The adjuvanted vaccine also induced functional antigen-specific cytotoxicity in vivo. Furthermore, we found that when fragmenting the Gag p24 protein into overlapping Gag p24 peptides, a broader T-cell epitope specificity was induced in the humanized human leukocyte antigen (HLA)-A2/DR-transgenic mouse model. Thus, combining overlapping Gag p24 peptides with CAF05 appears to be a promising and simple strategy for inducing broader T-cell responses to multiple conserved epitopes which will be relevant for both prophylactic and therapeutic HIV-1 vaccines.",
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Broadening of the T-cell repertoire to HIV-1 Gag p24 by vaccination of HLA-A2/DR transgenic mice with overlapping peptides in the CAF05 adjuvant. / Korsholm, Karen S; Karlsson, Ingrid; Tang, Sheila T; Brandt, Lea; Agger, Else Marie; Aagaard, Claus; Andersen, Peter; Fomsgaard, Anders.

I: PLOS ONE, Bind 8, Nr. 5, 2013, s. e63575.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Broadening of the T-cell repertoire to HIV-1 Gag p24 by vaccination of HLA-A2/DR transgenic mice with overlapping peptides in the CAF05 adjuvant

AU - Korsholm, Karen S

AU - Karlsson, Ingrid

AU - Tang, Sheila T

AU - Brandt, Lea

AU - Agger, Else Marie

AU - Aagaard, Claus

AU - Andersen, Peter

AU - Fomsgaard, Anders

PY - 2013

Y1 - 2013

N2 - Induction of broad T-cell immune responses is regarded as critical for vaccines against the human immunodeficiency virus type 1 (HIV-1) which exhibit high diversity and, therefore, focus has been on inducing cytotoxic CD8 T-cell responses against the more conserved parts of the virus, such as the Gag protein. Herein, we have used the p24 protein which contains a range of conserved T-cell epitopes. We demonstrate that a vaccine of HIV-1 subtype B consensus group-specific antigen (Gag) p24 protein with the CD8-inducing liposomal cationic adjuvant formulation (CAF) 05, induces both CD4 and CD8 T-cell responses in CB6F1 mice. The adjuvanted vaccine also induced functional antigen-specific cytotoxicity in vivo. Furthermore, we found that when fragmenting the Gag p24 protein into overlapping Gag p24 peptides, a broader T-cell epitope specificity was induced in the humanized human leukocyte antigen (HLA)-A2/DR-transgenic mouse model. Thus, combining overlapping Gag p24 peptides with CAF05 appears to be a promising and simple strategy for inducing broader T-cell responses to multiple conserved epitopes which will be relevant for both prophylactic and therapeutic HIV-1 vaccines.

AB - Induction of broad T-cell immune responses is regarded as critical for vaccines against the human immunodeficiency virus type 1 (HIV-1) which exhibit high diversity and, therefore, focus has been on inducing cytotoxic CD8 T-cell responses against the more conserved parts of the virus, such as the Gag protein. Herein, we have used the p24 protein which contains a range of conserved T-cell epitopes. We demonstrate that a vaccine of HIV-1 subtype B consensus group-specific antigen (Gag) p24 protein with the CD8-inducing liposomal cationic adjuvant formulation (CAF) 05, induces both CD4 and CD8 T-cell responses in CB6F1 mice. The adjuvanted vaccine also induced functional antigen-specific cytotoxicity in vivo. Furthermore, we found that when fragmenting the Gag p24 protein into overlapping Gag p24 peptides, a broader T-cell epitope specificity was induced in the humanized human leukocyte antigen (HLA)-A2/DR-transgenic mouse model. Thus, combining overlapping Gag p24 peptides with CAF05 appears to be a promising and simple strategy for inducing broader T-cell responses to multiple conserved epitopes which will be relevant for both prophylactic and therapeutic HIV-1 vaccines.

KW - AIDS Vaccines

KW - Amino Acid Sequence

KW - Analysis of Variance

KW - Animals

KW - CD8-Positive T-Lymphocytes

KW - Enzyme-Linked Immunosorbent Assay

KW - Enzyme-Linked Immunospot Assay

KW - Epitopes, T-Lymphocyte

KW - HIV Core Protein p24

KW - HIV-1

KW - HLA-A2 Antigen

KW - Immunity, Cellular

KW - Mice

KW - Mice, Transgenic

KW - Molecular Sequence Data

U2 - 10.1371/journal.pone.0063575

DO - 10.1371/journal.pone.0063575

M3 - Journal article

C2 - 23691069

VL - 8

SP - e63575

JO - P L o S One

JF - P L o S One

SN - 1932-6203

IS - 5

ER -