Circumventing genetic restriction of protection against malaria with multigene DNA immunization: CD8+ cell-, interferon γ-, and nitric oxide-dependent immunity

Doolan, Denise L., Sedegah, Martha, Hedstrom, Richard C., Hobart, Peter, Charoenvit, Yupin, and Hoffman, Stephen L. (1996) Circumventing genetic restriction of protection against malaria with multigene DNA immunization: CD8+ cell-, interferon γ-, and nitric oxide-dependent immunity. The Journal of Experimental Medicine, 183 (4). pp. 1739-1746.

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Abstract

Despite efforts to develop vaccines that protect against malaria by inducing CD8+ T cells that kill infected hepatocytes, no subunit vaccine has been shown to circumvent the genetic restriction inherent in this approach, and little is known about the interaction of subunit vaccine-induced immune effectors and infected hepatocytes. We now report that immunization with plasmid DNA encoding the plasmodium yoelii circumsporozoite protein protected one of five strains of mice against malaria (H-2d, 75%); a PyHEP17 DNA vaccine protected three of the five strains (H-2a, 71%; H-2k, 54%; H-2d, 26%); and the combination protected 82% of H-2a, 90% of H-2k, and 88% of H-2d mice. Protection was absolutely dependent on CD8+ T cells, INF-γ, or nitric oxide. These data introduce a new target of protective preerythrocytic immune responses, PyHEP 17 and its P. falciparum homologue, and provide a realistic perspective on the opportunities and challenges inherent in developing malaria vaccines that target the infected hepatocyte.

Item ID: 42779
Item Type: Article (Refereed Research - C1)
ISSN: 1540-9538
Funders: Naval Medical Research and Development Command (NMRDC)
Projects and Grants: NMRDC Work Unit No. 62787A00101EVX, NMRDC Work Unit No. 61102A.00101-BFX, NMRDC Work Unit No. 62787A00101EFX
Date Deposited: 14 Sep 2016 23:29
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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