Plasmodium falciparum sporozoite invasion is inhibited by naturally acquired or experimentally induced polyclonal antibodies to the STARP antigen

Abstract

Antibody(Ab)-mediated inhibition of sporozoite invasion of hepatocytes is a mechanism that has been clearly demonstrated to act upon Plasmodium falciparum pre-erythrocytic stages in humans. Consequently we have analyzed the Ab response to a recently identified P. falciparum sporozoite surface protein, STARP, in malaria-exposed individuals and tested the inhibitory effect of these Ab upon hepatocyte invasion in vitro. STARP-specific IgG were detected in 90 and 61% of sera from regions where individuals were exposed to 100 and 1-5 infectious bites per year, respectively. These IgG were predominantly of the cytophilic IgG1 or IgG3 type. STARP and the major sporozoite surface protein, CS, elicited equivalent IgG levels in adults. When affinity purified from either African immune sera or the serum of an individual experimentally protected by irradiated sporozoite immunization, STARP-specific Ab prevented up to 90% of sporozoites from invading human hepatocytes. The dose-dependent and reproducible inhibition was more pronounced than that observed with human CS-specific Ab affinity purified under identical conditions. Substantial reduction of sporozoite invasion was also observed with Ab induced by artificial immunization with recombinant STARP protein and reactive with the native protein. Taken together with recent findings of human cytotoxic T lymphocytes specific for this antigen, these results promote the interest of studying the efficacy of STARP as a target for immune effector mechanisms operating upon pre-erythrocytic stages.

Interferon-γ, a valuable surrogate marker of Plasmodium falciparum pre-erythrocytic stages protective immunity

“…Further work conducted in vitro in primary hepatocyte cultures has indicated a strong sporozoite-invasion inhibitory effect by antibodies both for rodent and for human malaria. This was shown to be true for Abs specific to a wide range of antigens such as CS [71,72], STARP [73], LSA3 [74], SALSA (Pasqueto, V. and Druilhe, P. unpublished data), TRAP [75], AMA-1 [76] as well as when using African adults sera which contain a wide range of antibody specificities [13]. Sporozoite invasion inhibition was also confirmed by in vivo passive transfer experiments [77,78].…”

A multiplex assay for the simultaneous detection of antibodies against 15 Plasmodium falciparum and Anopheles gambiae saliva antigens

“…Ab responses against LSA-1 derived peptides have been previously shown to correlate with the cumulative exposure to malaria transmission [24]. Liver stage antigen 3 (LSA-3) [25], sporozoite threonine- and asparagine-rich protein (Starp) [23] and sporozoite- and liver-stage antigen (Salsa) are expressed at both the sporozoite and hepatic stages [26] and have been reported as antigenic [26,27]. SR11.1 Ag corresponds to a unique subregion of the megaprotein Pf 11.1 (Brahimi K., et al unpublished data; Perlaza B.L., et al unpublished data), and it is expressed at sporozoite and liver stages.…”

Pre-Erythrocytic Vaccine Candidates in Malaria

“…People in malaria endemic regions produce antibody to ST"RP [190 192], with the percentage of the population related to the rate of exposure to malaria [193]. The main ST"RP antibody response in "fricans naturally exposed to malaria or volunteers immunized with irradiated sporozoites was to the Rp10 peptide, and puriied antibody prevented 90% of the sporozoites from infecting human liver cells in vitro [193].…”

“…The main ST"RP antibody response in "fricans naturally exposed to malaria or volunteers immunized with irradiated sporozoites was to the Rp10 peptide, and puriied antibody prevented 90% of the sporozoites from infecting human liver cells in vitro [193]. In West "frican children, the presence of antibody to ST"RP was associated with protection from malaria [171]. "…”