Construction and characterisation of a candidate HIV-1 subtype C DNA vaccine for South Africa

A candidate DNA vaccine pTHgagC expressing the immunodeficiency virus-1 (HIV-1) gag gene from South African isolate Du422 was constructed and characterised. The isolate was selected on the basis of being the closest to the South African subtype C consensus sequence. Sequence analysis of cytotoxic T...

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Veröffentlicht in:Vaccine 2003-10, Vol.21 (27), p.4380-4389
Hauptverfasser: van Harmelen, Joanne H., Shephard, Enid, Thomas, Robin, Hanke, Tomáš, Williamson, Anna-Lise, Williamson, Carolyn
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container_end_page 4389
container_issue 27
container_start_page 4380
container_title Vaccine
container_volume 21
creator van Harmelen, Joanne H.
Shephard, Enid
Thomas, Robin
Hanke, Tomáš
Williamson, Anna-Lise
Williamson, Carolyn
description A candidate DNA vaccine pTHgagC expressing the immunodeficiency virus-1 (HIV-1) gag gene from South African isolate Du422 was constructed and characterised. The isolate was selected on the basis of being the closest to the South African subtype C consensus sequence. Sequence analysis of cytotoxic T lymphocyte (CTL) epitopes showed that HIV subtype C-infected individuals have CTL responses to a number of epitopes present in the vaccine, but also revealed a more limited presence of subtype A- and any B-derived epitopes. A high level of expression of the immunogen was demonstrated in human cells and a potent, long-lived CTL response to a single inoculation of the DNA vaccine was elicited in BALB/c mice, which could be significantly increased by a boost vaccination at 4 weeks. This is the first candidate HIV-1 DNA vaccine employing the South African subtype C sequences, and constitutes a part of a vaccine scheduled to enter a clinical evaluation in South Africa in 2004.
doi_str_mv 10.1016/S0264-410X(03)00406-7
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The isolate was selected on the basis of being the closest to the South African subtype C consensus sequence. Sequence analysis of cytotoxic T lymphocyte (CTL) epitopes showed that HIV subtype C-infected individuals have CTL responses to a number of epitopes present in the vaccine, but also revealed a more limited presence of subtype A- and any B-derived epitopes. A high level of expression of the immunogen was demonstrated in human cells and a potent, long-lived CTL response to a single inoculation of the DNA vaccine was elicited in BALB/c mice, which could be significantly increased by a boost vaccination at 4 weeks. 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The isolate was selected on the basis of being the closest to the South African subtype C consensus sequence. Sequence analysis of cytotoxic T lymphocyte (CTL) epitopes showed that HIV subtype C-infected individuals have CTL responses to a number of epitopes present in the vaccine, but also revealed a more limited presence of subtype A- and any B-derived epitopes. A high level of expression of the immunogen was demonstrated in human cells and a potent, long-lived CTL response to a single inoculation of the DNA vaccine was elicited in BALB/c mice, which could be significantly increased by a boost vaccination at 4 weeks. This is the first candidate HIV-1 DNA vaccine employing the South African subtype C sequences, and constitutes a part of a vaccine scheduled to enter a clinical evaluation in South Africa in 2004.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>14505921</pmid><doi>10.1016/S0264-410X(03)00406-7</doi><tpages>10</tpages></addata></record>
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source MEDLINE; Elsevier ScienceDirect Journals; ProQuest Central UK/Ireland
subjects AIDS Vaccines - immunology
Amino Acid Sequence
Animals
Biological and medical sciences
Chromium Radioisotopes
Clinical trials
Construction
Cytotoxicity Tests, Immunologic
Deoxyribonucleic acid
DNA
DNA vaccination
DNA, Complementary - immunology
Fundamental and applied biological sciences. Psychology
Gag
Genes
Genes, gag - genetics
Genomes
HeLa Cells
HIV
HIV-1 - immunology
HIV-1 subtype C
Human immunodeficiency virus
Human immunodeficiency virus 1
Humans
Immunization
Interferon-gamma - metabolism
Lymphocytes
Mice
Mice, Inbred BALB C
Microbiology
Molecular Sequence Data
Peptides
Proteins
South Africa
T-Lymphocytes, Regulatory - immunology
Vaccines
Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies
Vaccines, DNA - immunology
Virology
Viruses
title Construction and characterisation of a candidate HIV-1 subtype C DNA vaccine for South Africa
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