PMID- 15483462
OWN - NLM
STAT- MEDLINE
DCOM- 20051026
LR  - 20200930
IS  - 1525-4135 (Print)
IS  - 1525-4135 (Linking)
VI  - 37
IP  - 3
DP  - 2004 Nov 1
TI  - Protective efficacy of multiepitope human leukocyte antigen-A*0201 restricted 
      cytotoxic T-lymphocyte peptide construct against challenge with human T-cell 
      lymphotropic virus type 1 Tax recombinant vaccinia virus.
PG  - 1329-39
AB  - Human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of adult 
      T-cell leukemia. Multiepitope T-cell vaccines are more likely to generate a broad 
      long-lasting immune response than those composed of single epitopes. We recently 
      reported a novel multivalent cytotoxic T-lymphocyte peptide construct derived 
      from the Tax protein of HTLV-1 separated by arginine spacers that elicited high 
      cellular responses against individual epitopes simultaneously in human leukocyte 
      antigen (HLA)-A*0201 transgenic mice. We now report the effect of epitope 
      orientation on the processing of the multiepitope construct by 20s proteasomes 
      and the effect of the processing rates on the immunogenicity of the intended 
      epitopes. A positive correlation was found between processing rates and the 
      immunogenicity of the intended epitopes. The construct with the highest 
      immunogenicity for each epitope was tested for protective efficacy in a 
      preclinical model of infection using HTLV-1 Tax recombinant vaccinia virus and 
      HLA-A*0201 transgenic mice. Mice vaccinated with the multiepitope construct 
      displayed a statistically significant reduction in viral replication that was 
      dependent on CD8 T cells. Reduction in viral replication was also confirmed to be 
      specific to Tax-vaccinia virus. These results demonstrate the activation of 
      Tax-specific CD8+ T cells by vaccination and are supportive of a multivalent 
      peptide vaccine approach against HTLV-1 infections.
FAU - Sundaram, Roshni
AU  - Sundaram R
AD  - Department of Obstetrics and Gynecology, The Ohio State University, Columbus, OH, 
      USA.
FAU - Lynch, Marcus P
AU  - Lynch MP
FAU - Rawale, Sharad
AU  - Rawale S
FAU - Dakappagari, Naveen
AU  - Dakappagari N
FAU - Young, Donn
AU  - Young D
FAU - Walker, Christopher M
AU  - Walker CM
FAU - Lemonnier, Francois
AU  - Lemonnier F
FAU - Jacobson, Steven
AU  - Jacobson S
FAU - Kaumaya, Pravin T P
AU  - Kaumaya PT
LA  - eng
GR  - A140302/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Acquir Immune Defic Syndr
JT  - Journal of acquired immune deficiency syndromes (1999)
JID - 100892005
RN  - 0 (Epitopes)
RN  - 0 (Gene Products, tax)
RN  - 0 (H-2 Antigens)
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-A*02:01 antigen)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Histocompatibility Antigen H-2D)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - CD8-Positive T-Lymphocytes/immunology/virology
MH  - Epitopes
MH  - Gene Products, tax/*immunology
MH  - H-2 Antigens/genetics/immunology
MH  - HLA-A Antigens/*genetics/immunology/therapeutic use
MH  - HLA-A2 Antigen
MH  - Histocompatibility Antigen H-2D
MH  - Human T-lymphotropic virus 1/*immunology
MH  - Humans
MH  - Mice
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Molecular Sequence Data
MH  - T-Lymphocytes, Cytotoxic/drug effects/*immunology
MH  - Vaccinia virus/genetics/*immunology
EDAT- 2004/10/16 09:00
MHDA- 2005/10/27 09:00
CRDT- 2004/10/16 09:00
PHST- 2004/10/16 09:00 [pubmed]
PHST- 2005/10/27 09:00 [medline]
PHST- 2004/10/16 09:00 [entrez]
AID - 00126334-200411010-00001 [pii]
AID - 10.1097/00126334-200411010-00001 [doi]
PST - ppublish
SO  - J Acquir Immune Defic Syndr. 2004 Nov 1;37(3):1329-39. doi: 
      10.1097/00126334-200411010-00001.