Induction of antigen-specific cytotoxic T lymphocytes in humans by a malaria DNA vaccine

R Wang, DL Doolan, TP Le, RC Hedstrom, KM Coonan… - Science, 1998 - science.org
R Wang, DL Doolan, TP Le, RC Hedstrom, KM Coonan, Y Charoenvit, TR Jones, P Hobart…
Science, 1998science.org
CD8+ cytotoxic T lymphocytes (CTLs) are critical for protection against intracellular
pathogens but often have been difficult to induce by subunit vaccines in animals. DNA
vaccines elicit protective CD8+ T cell responses. Malaria-naı̈ve volunteers who were
vaccinated with plasmid DNA encoding a malaria protein developed antigen-specific,
genetically restricted, CD8+ T cell–dependent CTLs. Responses were directed against all
10 peptides tested and were restricted by six human lymphocyte antigen (HLA) class I …
CD8+ cytotoxic T lymphocytes (CTLs) are critical for protection against intracellular pathogens but often have been difficult to induce by subunit vaccines in animals. DNA vaccines elicit protective CD8+ T cell responses. Malaria-naı̈ve volunteers who were vaccinated with plasmid DNA encoding a malaria protein developed antigen-specific, genetically restricted, CD8+ T cell–dependent CTLs. Responses were directed against all 10 peptides tested and were restricted by six human lymphocyte antigen (HLA) class I alleles. This first demonstration in healthy naı̈ve humans of the induction of CD8+ CTLs by DNA vaccines, including CTLs that were restricted by multiple HLA alleles in the same individual, provides a foundation for further human testing of this potentially revolutionary vaccine technology.
AAAS