Strategy for development of a pre-erythrocytic Plasmodium falciparum DNA vaccine for human use

Hoffman, Stephen L., Doolan, Denise L., Sedegah, Martha, Aguiar, Joao C., Wang, Ruobing, Malik, Anita, Gramzinski, Robert A., Weiss, Walter R., Hobart, Peter, Norman, Jon A., Margalith, Michal, and Hedstrom, Richard C. (1997) Strategy for development of a pre-erythrocytic Plasmodium falciparum DNA vaccine for human use. Vaccine, 15 (8). pp. 842-845.

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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.

Item ID: 42776
Item Type: Article (Research - C1)
ISSN: 1873-2518
Keywords: DNA vaccine; malaria; pre-erythrocytic stage
Funders: Naval Medical Research and Development Command (NMRDC)
Projects and Grants: NMRDC Work Unit STO.F.1432, NMRDC Work Unit STO.F.1433
Date Deposited: 14 Sep 2016 03:34
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110799 Immunology not elsewhere classified @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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