INDUCTION OF ANTIGEN-SPECIFIC CYTOTOXIC T-LYMPHOCYTES IN HUMANS BY A MALARIA DNA VACCINE

CD8(+) cytotoxic T lymphocytes (CTLs) are critical for protection agai nst intracellular pathogens but often have been difficult to induce by subunit vaccines in animals. DNA vaccines elicit protective CD8(+) T cell responses. Malaria-naive volunteers who were vaccinated with plas mid DNA encoding a malaria protein developed antigen-specific, genetic ally restricted, CD8(+) T cell-dependent CTLs. Responses were directed against all 10 peptides tested and were restricted by six human lymph ocyte antigen (HLA) class I alleles. This first demonstration in healt hy naive humans of the induction of CD8(+) CTLs by DNA vaccines, inclu ding CTLs that were restricted by multiple HLA alleles in the same ind ividual, provides a foundation for further human testing of this poten tially revolutionary vaccine technology.