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Infection and Immunity, March 2007, p. 1177-1185, Vol. 75, No. 3
0019-9567/07/$08.00+0     doi:10.1128/IAI.01667-06

A Novel Chimeric Plasmodium vivax Circumsporozoite Protein Induces Biologically Functional Antibodies That Recognize both VK210 and VK247 Sporozoites{triangledown}

Anjali Yadava,1* Jetsumon Sattabongkot,2 Michael A. Washington,1 Lisa A. Ware,1 Victoria Majam,3 Hong Zheng,3 Sanjai Kumar,3 and Christian F. Ockenhouse1

Division of Malaria Vaccine Development, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, Maryland 20910,1 Department of Entomology, U.S. Army Medical Component, Armed Forces Research Institute of Medical Sciences, 315/6 Rajvithi Road, Bangkok 10400, Thailand,2 Center for Biologics Evaluation and Research, Food and Drug Administration, 5516 Nicholson Lane, Kensington, Maryland 208953

Received 18 October 2006/ Returned for modification 29 November 2006/ Accepted 1 December 2006

A successful vaccine against Plasmodium vivax malaria would significantly improve the health and quality of the lives of more than 1 billion people around the world. A subunit vaccine is the only option in the absence of long-term culture of P. vivax parasites. The circumsporozoite protein that covers the surface of Plasmodium sporozoites is one of the best-studied malarial antigens and the most promising vaccine in clinical trials. We report here the development of a novel "immunologically optimal" recombinant vaccine expressed in Escherichia coli that encodes a chimeric CS protein encompassing repeats from the two major alleles, VK210 and VK247. This molecule is widely recognized by sera from patients naturally exposed to P. vivax infection and induces a highly potent immune response in genetically disparate strains of mice. Antibodies from immunized animals recognize both VK210 and VK247 sporozoites. Furthermore, these antibodies appear to be protective in nature since they cause the agglutination of live sporozoites, an in vitro surrogate of sporozoite infectivity. These results strongly suggest that recombinant CS is biologically active and highly immunogenic across major histocompatibility complex strains and raises the prospect that in humans this vaccine may induce protective immune responses.

* Corresponding author. Mailing address: Division of Malaria Vaccine Development, Walter Reed Army Institute of Research, Silver Spring, MD 20910. Phone: (301) 319-9577. Fax: (301) 319-7358. E-mail: anjali.yadava{at}us.army.mil.

{triangledown} Published ahead of print on 11 December 2006.

Editor: W. A. Petri, Jr.

Infection and Immunity, March 2007, p. 1177-1185, Vol. 75, No. 3
0019-9567/07/$08.00+0     doi:10.1128/IAI.01667-06






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