Immunity to Malaria and Naturally Acquired Antibodies to the Circumsporozoite Protein ofPlasmodium falciparum

Abstract

A candidate Plasmodium falciparum sporozoite vaccine, R32tet32, which includes 32 tetrapeptide repeats derived from the circumsporozoite protein of P. falciparum, has been developed on the basis of the hypothesis that antibodies to the repeat region of this protein will protect against sporozoite infection. The results of two in vitro assays, the circumsporozoite precipitation reaction and the inhibition of sporozoite invasion into hepatoma cells, are thought to indicate protective immunity. We therefore tested serum samples from persons living in a hyperendemic malarious area of Indonesia for antibodies against R32tet32 and for their ability to produce circumsporozoite precipitation and to inhibit sporozoite invasion of hepatoma cells. The prevalence and mean titer of antibody against R32tet32 increased with the age of the subjects, whereas the prevalence of P. falciparum infection in the community decreased. Only serum samples with IgG or IgM R32tet32 antibody titers greater than or equal to 1/800 had precipitation activity and invasion-inhibiting activity of more than 75 percent. When the serum samples were fractionated by affinity chromatography, only the fractions containing purified human antibody to R32tet32 were found to contain this activity. These data support the hypotheses that antibodies to the circumsporozoite protein are important in reducing the prevalence of malaria with increasing age among persons in areas in which malaria is endemic and that vaccine-elicited antibody to the circumsporozoite repeat region will protect against infection with P. falciparum sporozoites.

Protection against Plasmodium falciparum malaria by PfSPZ Vaccine

“…Through the mid-1980s it was thought that antibodies to PfSPZ, particularly to the PfCSP, that blocked sporozoite invasion of hepatocytes were responsible for irradiated SPZ-induced protection (14,15). However, when it was shown that treatment of fully immune mice (6,(16)(17)(18) and non-human primates (19) with anti-CD8 antibodies eliminated the protective immunity, it was hypothesized that cellular immune responses against the developing liver stages were responsible for protection (16,17,(20)(21)(22)(23).…”

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

“…43,44 Additionally, anti-CS antibodies appear to be associated with protection against natural exposure of vaccinated 45,46 and non-vaccinated human volunteers. 47,48 Although a recent study indicates that there appears to be no association between levels of anti-CS antibodies and protection, 49 a possible explanation for these discrepancies may be the different antigens used for antibody detection. The CS antigen is a large protein with numerous B-cell epitopes distributed along its entire sequence and therefore while antibodies to certain regions might not be associated with protection, antibodies to epitopes comprising or related to functional domains, i.e., those comprising region I within the N region may block the protein cleavage necessary for parasite invasion and are likely to be associated with protection.…”

Antibodies to Plasmodium falciparum sporozoites following a malarial outbreak in a non-endemic area of Sri Lanka

“…However, due to the scarcity of antigen used for both these techniques, thev were of limited applicabilitv in epidemiological studies. The cloning bf the ci&umsporozoite TCS) orotein antigen of P. falcibarum and the elucidation of its structuri (DAME et ai., 1984;ENEA et al, 1984;NUSSENZWEI~~ & NUSSEN~WEIG,~~~~) paved the way for the use of recombinant (HOFFMAN et al. 1986) and synthetic antigens (ZAV~LA er al., 1986;'CAMP: Author for correspondence: M. de S. Wijesundera, Department of Parasitology, Faculty of Medicine, Peradeniya, Sri Lanka.…”