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Induction of CD4+ T cell-dependent CD8+ type 1 responses in humans by a malaria DNA vaccine
- 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‖, and
- Stephen L. Hoffman*,††
- *Malaria Program, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD 20910; †Henry M. Jackson Foundation, Rockville, MD 20852; §United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702; ‖Vical Incorporated, San Diego, CA 92121; **Bioject Inc., Portland, OR 97224; and ‡‡School of Hygiene and Public Health, Johns Hopkins University, Baltimore, MD 21205-2129
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Edited by Maurice R. Hilleman, Merck Institute for Vaccinology, West Point, PA, and approved June 1, 2001 (received for review March 13, 2001)
Abstract
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.
Footnotes
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↵ ‡ R.W. and J.E. contributed equally to this work.
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↵ ¶ Present address: Pasteur Merieux Connaught USA, Swiftwater, PA 18370.
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↵ †† To whom reprint requests should be addressed at: Celera Genomics, 45 West Gude Drive, Rockville, MD 20850. E-mail: stephen.hoffman{at}celera.com.
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This paper was submitted directly (Track II) to the PNAS office.
- Abbreviations:
- PfCSP,
- P. falciparum circumsporozoite protein;
- CTL,
- cytotoxic T lymphocyte;
- SFCs,
- spot forming cells;
- APC,
- antigen-presenting cell;
- ELISPOT,
- enzyme-linked immunospot;
- PBMC,
- peripheral blood mononuclear cell;
- i.d.,
- intradermally
- Copyright © 2001, The National Academy of Sciences
