USA As Represented by Secretary of the Navy

Richard C Hedstrom

Stephen L Hoffman

Martha Sedegah

Yupin Charoenvit

Denise L Doolan

A first embodiment is a specific plasmid vector, pDIP/PyCSP.1, into which nucleotides encoding the targets of specific immune responses are inserted. These targets include, but are not limited to proteins and peptides. These plasmid constructs are incorporated in a composition comprising a suitable and acceptable art recognized pharmaceutical reagent that is benign (non-reactive with) to the plasmid construct. The plasmid construct provides protective immune responses to the disease associated with the selected targets. A second embodiment is a construct having, at a minimum, the nucleotide sequences encoding one or more Plasmodium species proteins in a pharmaceutically acceptable vector. a third embodiment is a method of controlling malaria in mammals comprising injecting a polynucleotide delivery vector into a mammal.

Polynucleotide vaccine protective against malaria, methods of protection

An IgG1 monoclonal antibody, Navy Yoelii Liver Stage 3 (NYLS3) does not recognize sporozoites, but recognizes P. yoelii liver stage parasites within 6 hours of invasion of mouse hepatocytes, and throughout the hepatic and asexual erythrocytic stages of the life cycle. When added to primary cultures of mouse hepatocytes 24 hours after inoculation with P. yoelii sporozoites, when all sporozoites have invaded hepatocytes, NYLS3 eliminates up to 98% of liver stage parasites. Intravenous injection of NYLS3 into mice delays the onset and reduces the density of blood stage parasitemia after sporozoite or blood stage challenge. The protein recognized by this mAb is identified and designated P. yoelii hepatic and erythrocytic stage protein, 17-kDa or PyHEP17. The gene encoding PyHEP17 and a DNA vaccine comprising exons of the DNA that encodes PyHEP17 are disclosed. A DNA vaccine consisting of exon 1 and part of exon 2 of the gene encoding PyHEP17 protects 86% of A/J mice, 33%-43% of B10.BR mice, 17%-29% of BALB/c mice and 14%-20% of B10.Q mice from development of blood-stage parasitemia. A combination of DNA vaccines consisting of a PyHEP17 DNA vaccine and a PyCSP DNA vaccine confers complete protection against development of blood-stage parasitemia in BALB/c mice and 71% protection in A/J and B10.BR mice. This DNA vaccine-induced protection may be additive. Combinations of other malaria antigens are covered. The application discloses the P. falciparum homolog of PyHEP17 and includes the means of identification of the PyHEP17 homologs of the other Plasmodium species which infect humans, specifically P. vivax, P. ovale and P. malariae.

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Gaithersburg, MD, United States of America

Richard C Hedstrom