Induction of CD4+T cell-dependent CD8+type 1 responses in humans by a malaria DNA vaccine

• DOI: 10.1073/pnas.181123498
• Publication Date: 2002-07-26T14:44:19Z
• Authors: Ruobing Wang; Judith Epstein; Fe Maria Baraceros; Edward J. Gorak; Yupin Charoenvit; Daniel J. Carucci; Richard C. Hedstrom; Nancy Rahardjo; Tanya Gay; Peter Hobart; Rick Stout; Trevor R. Jones; Thomas L. Richie; Suezanne E. Parker; Denise L. Doolan; Jon Norman; Stephen L. Hoffman
• Keywords: Adult; CD4-Positive T-Lymphocytes; 0301 basic medicine; Adolescent; Molecular Sequence Data; Plasmodium falciparum; Protozoan Proteins; Antigens, Protozoan; DNA, Protozoan; 3. Good health; Interferon-gamma; 03 medical and health sciences; T-Lymphocyte Subsets; Malaria Vaccines; Vaccines, DNA; Animals; Humans; Amino Acid Sequence; Interleukin-4; Malaria, Falciparum; T-Lymphocytes, Cytotoxic

We assessed immunogenicity of a malaria DNA vaccine administered by needle i.m. or needleless jet injection [i.m. or i.m./intradermally (i.d.)] in 14 volunteers. Antigen-specific IFN-γ responses were detected by enzyme-linked immunospot (ELISPOT) assays in all subjects to multiple 9- to 23-aa peptides containing class I and/or class II restricted epitopes, and were dependent on both CD8+and CD4+T cells. Overall, frequency of response was significantly greater after i.m. jet injection. CD8+-dependent cytotoxic T lymphocytes (CTL) were detected in 8/14 volunteers. Demonstration in humans of elicitation of the class I restricted IFN-γ responses we believe necessary for protection against the liver stage of malaria parasites brings us closer to an effective malaria vaccine.