A Multicomponent Vaccine For Malaria Providing Long-lasting Immune Responses Against Plasmodia (2)
This application relates to immunogenic conjugates which elicit an immune response to Plasmodium proteins. This application claims conjugates that include at least one Plasmodium sexual stage surface protein covalently linked to at least one Plasmodium circumsporozoite protein (CSP) or an immunogenic portion of a CSP. Also claimed are conjugates that include at least one sexual stage surface protein covalently linked to at least one immunogenic repeat derived from a Plasmodium CSP. The inventors' data shows that these conjugates also induced long-lasting antibody responses to each of their components, i.e. the vaccine candidates showed both transmission blocking activity and antibodies to the CSP (or portion thereof). The inventors have previously shown that P. falciparum conjugates of the ookinete surface protein Pfs25 are immunogenic and induce long-lasting IgG antibody responses in mice. The inventors have also previously shown that adsorption of the conjugates onto aluminum hydroxide further increased the antibody response. Remarkably, the antibody levels three or seven months after the last injection were significantly higher than those one week after that injection. Such a vaccine would block disease transmission if most/all the population is immunized. Plasmodium falciparum causes the most severe form of malaria; one to three percent of the parasites are highly virulent, causing the death of approximately two million people annually, ninety percent of whom are young children. Plasmodium vivax is the most widespread cause of malaria. There is as yet no licensed prophylactic vaccine for this disease. Furthermore, malarial parasites are increasingly becoming resistant to antimalarial drugs that have been used to treat the disease for decades.
Granted Patent Reference Number(s): US Application No. 13/121,574, filed 03/29/2011.; HHS Reference No. E-339-2008/0,1,2; CN Application No. 200980148315.8; IN Application No.1382/KOLNP/2011; EP Application No. 09818532.5; PCT/US2009/0592884, filed 10/01/2009