Strategy for development of a pre-erythrocytic Plasmodium falciparum DNA vaccine for human use
| Autor: | Denise L. Doolan, Robert A. Gramzinski, Richard C. Hedstrom, Joao C. Aguiar, Ruobing Wang, Martha Sedegah, Stephen L. Hoffman, Walter R. Weiss, Anita Malik, Peter Hobart, Jon Norman, Michal Margalith |
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| Rok vydání: | 1997 |
| Předmět: |
Erythrocytes
Plasmodium falciparum Protozoan Proteins Antigens Protozoan law.invention DNA vaccination Mice Plasmid law Malaria Vaccines parasitic diseases Vaccines DNA Animals Humans Malaria Falciparum Gene Mice Inbred BALB C General Veterinary General Immunology and Microbiology biology Immunogenicity Public Health Environmental and Occupational Health Plasmodium yoelii DNA Protozoan biology.organism_classification Virology Malaria Circumsporozoite protein Disease Models Animal Infectious Diseases Recombinant DNA Molecular Medicine |
| Zdroj: | Vaccine. 15:842-845 |
| ISSN: | 0264-410X |
| DOI: | 10.1016/s0264-410x(96)00273-3 |
| Popis: | Data generated in the Plasmodium yoelii rodent model indicated that plasmid DNA vaccines encoding the P. yoelii circumsporozoite protein (PyCSP) or 17 kDa hepatocyte erythrocyte protein (PyHEP17) were potent inducers of protective CD8+ T cell responses directed against infected hepatocytes. Immunization with a mixture of these plasmids circumvented the genetic restriction of protective immunity and induced additive protection. A third DNA vaccine encoding the P. yoelii sporozoite surface protein 2 (PySSP2) also induced protection. The P. falciparum genes encoding the homologues of these three protective P. yoelii antigens as well as another P. falciparum gene encoding a protein that is expressed in infected hepatocytes have been chosen for the development of a human vaccine. The optimal plasmid constructs for human use will be selected on the basis of immunogenicity data generated in mice and nonhuman primates. We anticipate that optimization of multi-gene P. falciparum DNA vaccines designed to protect against malaria by inducing CD8+ T cells that target infected hepatocytes will require extensive clinical trials during the coming years. |
| Databáze: | OpenAIRE |
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