Circumsporozoite proteins of human malaria parasites Plasmodium falciparum and Plasmodium vivax.

Abstract

The malaria sporozoite injected into a host by the bite of the mosquito vector initiates the parasite cycle that culminates in clinical disease. This sporozoite stage is highly antigenic, and immunization with irradiated sporozoites has prevented the development of malaria in rodent and simian hosts as well as in several human volunteers (1). Antisporozoite antibodies detectable in the sera of the immunized primate hosts appear to be associated with immune resistance.Recently, hybridoma-derived monoclonal antibodies directed against sporozoites of rodent and simian malaria were found to be protective, i.e., to abolish sporozoite infectivity both in vivo (2) and in vitro (3). 1 These antibodies react with circumsporozoite (CS) 2 proteins; that is, stage-and species-specific polypeptides that are uniformly distributed over the entire surface of the parasite and that are shed when cross-linked by antibodies (2, 4). 1The hybridoma technique was therefore used to develop monoclonal antibodies against sporozoites of P falciparum and P. vivax in an attempt to identify the protective antigens of the human pathogens for their application in a vaccine. Materials and MethodsMice. BALB/c mice were immunized using viable and frozen sporozoites of P.falciparum or P. vivax. The P. falciparum spomzoites were of West African origin and were obtained by membrane feeding Anopheles gambiae mosquitoes on blood obtained from patients carrying P. falciparum gametoeytes. P. vivax sporozoites for immunization were obtained from Anopheles

Preclinical Vaccine Study of Plasmodium vivax Circumsporozoite Protein Derived-Synthetic Polypeptides Formulated in Montanide ISA 720 and Montanide ISA 51 Adjuvants

“…Although there are contrasting results regarding the protective role of anti-CS antibodies, it has been repeatedly shown that they are able to in vitro inhibit sporozoite invasion to hepatic cells, [40][41][42] to prevent infection in mice and monkeys injected with live sporozoites. 43,44 Additionally, anti-CS antibodies appear to be associated with protection against natural exposure of vaccinated 45,46 and non-vaccinated human volunteers.…”

Anopheles stephensi salivary glands bear receptors for region I of the circumsporozoite protein of Plasmodium falciparum

“…The recombinant CS used in these studies was kindly provided by Dr Bela Takacs (F. Hoffmann-La Roche, Basel, Switzerland). The monoclonal antibody (mAb) 2A10 is directed against an epitope contained in the (NANP) n repeat domain of P. falciparum CS [10]. The yeast-derived recombinant construct TBV25H [11] represents the entire P. falciparum surface protein (Pfs25) coding region, excepting the N-terminal secretory signal sequence and the hydrophobic carboxy-terminus (residues 1-22 and 193-202), and includes six terminal histidines added for purification purposes.…”

Different prevalences of Plasmodium vivax phenotypes VK210 and VK247 associated with the distribution of Anopheles albimanus and Anopheles pseudopunctipennis in Mexico.

“…20 Parasite phenotype identification was carried out using monoclonal antibodies that recognize either the P. vivax CS protein-210 repeat region or the CS protein-247 repeat region. 21 These assays and the genotyping analysis were performed blinded to the results of entomologic and demographic investigations.…”