PAGE TITLE
Plasmodium liver stage antigens for malaria vaccine and diagnostics
PAGE SUMMARY
There are an estimated 200-300 million people infected with malaria annually, with a mortality rate of 1-3%, and 40% of the world’s population at risk of contracting the disease. While the RTS,S (Mosquirix, GSK) recombinant protein-based vaccine is a breakthrough as the first vaccine candidate in pilot studies for countering parasites, the efficacy remains low (25-50% in infants and children).
Malaria infection begins when the Anopheles mosquito injects infective sporozoites into the mammalian host. Sporozoites travel through different cells before settling into their final host hepatocyte. The sporozoite moves into a vacuole created by invagination of the hepatocyte plasma membrane. Inside this compartment, the sporozoite transforms into a liver stage, which grows rapidly and undergoes multiple rounds of nuclear division. The mature liver stage releases thousands of merozoites that will establish red blood cell infection in the host.
Liver stages are predicted to express many different proteins, some possibly unique to this stage, but only few of those unique molecules have been identified so far. Identification of liver stage-specific molecules is important because the infected hepatocyte has been established as the primary target of the immune response in vaccine models for malaria. In addition, liver stage molecules that can be detected in a human diagnostic sample may be useful for diagnosing early stage malaria.
Researchers in Drexel’s Department of Microbiology & Immunology, the Seattle Biomedical Research Institute, and the Walter Reed Army Institute of Research have isolated liver stage Plasmodium polypeptides. These proteins are preferentially targeted by immune responses associated with protection from Plasmodium infection and could be used in developing a new malaria vaccine.
APPLICATIONS
TITLE: Applications
Malaria vaccine design and production
Diagnostic marker for malaria
Induction of immune response against liver stage Plasmodium polypeptides
ADVANTAGES
TITLE:Advantages
Preferentially target immune response for Plasmodium infection
Novel recombinant or synthetic polypeptides
Target liver stage of malaria parasite
IP STATUS
Intellectual Property and Development Status
United States issued patent 7,722,889
https://patents.google.com/patent/US7722889B2/en?oq=7%2c722%2c889
United States issued patent 8,318,183
https://patents.google.com/patent/US8318183B2/en?oq=8%2c318%2c183
EU issued patent 1937715
PUBLICATIONS
References
Butler N.S. et al. Superior antimalarial immunity after vaccination with late liver stage-arresting genetically attenuated parasites. Cell Host and Microbe, 2011, 9(6), p. 451-462.
https://www.sciencedirect.com/science/article/pii/S1931312811001727
Tarun A.S. et al. A combined transcriptome and proteome survey of malaria parasite liver stages. PNAS, 2008, 105, p. 305-310.
http://europepmc.org/articles/PMC2224207
Tarun A.S. et al. Quantitative isolation and in vivo imaging of malaria parasite liver stages. International Journal for Parasitology, 2006, 36(12), p. 1283-1293.
https://www.sciencedirect.com/science/article/pii/S0020751906002396
Mikolajczak S.A. and Kappe S.H. A clash to conquer: the malaria parasite liver infection. Molecular Microbiology, 2006, 62(6), p. 1499-1506.
https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2958.2006.05470.x#references-section
Contact Information:
Robert McGrath
Sr AVP for IP & Agreements
RBM@Drexel.edu