Conformation-stabilized TRAP antigens for malaria vaccines
Inventors: Timothy Springer, Adem Koksal, Chafen Lu, Gaojie Song
Invention Types: Therapeutics, Research Tool
Research Areas: Immunology, Infectious Disease
Keywords: VaccineFor More Information Contact: Ives, Catherine L.
The purpose of pre-erythrocytic malaria vaccines is to induce sterilizing immunity to sporozoites, the form taken by malaria-causing Plasmodium parasites before invasion of hepatocytes, maturation into merozoites and infection of red blood cells. The sporozoite stage is an attractive target for vaccine development because there is generally only one gene per protein antigen target.
Researchers at Boston Children’s Hospital have characterized the structure of one the most important targets of pre-erythrocytic vaccines, Thrombospondin Repeat Anonymous Protein (TRAP), which is known to mediate sporozoite gliding motility and cell invasion in both hosts and carriers. Using x-ray crystallography, Tim Springer and colleagues identified both open and closed conformations of TRAP. This led to the development of a method for producing and optimizing antigens that allow for the generation of antibodies to either conformation. Immunization with their modified TRAP proteins demonstrated the production of high-titer antibodies in mice and rabbit models.
• Improved pre-erythrocytic malaria vaccines through the use of conformation-stabilized TRAP protein antigens to better evoke the generation of neutralizing antibodies.
• Research tool for various clinical and research applications including infectivity assays.
• Previous studies using TRAP protein antigens displayed relatively poor titers and no protection against infection.
• Expression, conformational heterogeneity, and antigenicity may be enhanced through various modifications to the engineered TRAP proteins.
• Conformation-specific TRAP antigens can be used separately or in conjunction to better stimulate an immune response.
Song G, Koksal AC, Lu C, Springer TA, 2012. Shape change in the receptor for gliding motility in Plasmodium sporozoites. PNAS 109(52): 21420-21425.
Swearingen KE, Lindner SE, Shi L, et al. Interrogating the Plasmodium sporozoite surface: Indentification of surface-exposed proteins and demonstration of glycosylation on CSP and TRAP by mass spectrometry-based proteomics. PLoS Pathog. 2016 Apr 29;12(4)
Related Publications: Pat. US 9,580,482 B2