Cellular immune response of humans to the circumsporozoite protein of Plasmodium vivax

Abstract

The cellular immune response to the circumsporozoite (CS) protein of Plasmodium vivax of individuals from malaria-endemic areas of Brazil was studied. We examined the in vitro proliferative response of the peripheral blood mononuclear cells (PBMC) of 22 individuals when stimulated with a CS recombinant protein (rPvCS-2) and two other synthetic peptides based on the sequence of the P. vivax CS protein. Seven of the individuals from malaria-endemic area displayed an antigen-specific in vitro proliferative response to the recombinant protein PvCS-2 and one out of 6, proliferative response to the peptide 308-320. In contrast, none of the individuals displayed a proliferative response when stimulated with the D/A peptide which represent some of the repeated units present in this CS protein. Our study, therefore, provides evidence for the presence, within the major surface antigen of P. vivax sporozoites, of epitopes capable to induce proliferation of human PBMC.

Low cellular response in vitro among subjects with long-term exposure to malaria transmission in Brazilian endemic areas.

“…11,15 Cells from adults who reported less than five years of malaria exposure in Brazilian endemic areas also had a significant proliferative response to CS proteins. 7,8,16 The high frequency of proliferative response now observed in the CB group is consistent with those earlier studies. However, a low level of in vitro cellular proliferative response to CS proteins in subjects continuously exposed to P. falciparum and P. vivax transmission for at least 10 years (Terra Nova do Norte group) is reported for the first time in Brazil.…”

“…In vitro tests of T cell proliferation against P. vivax CS protein showed that 32% of such subjects produced a positive response. 7 Parallel tests of cellular responsiveness to P. falciparum and P. vivax recombinant CS (rCS) proteins, performed in areas where both parasites are transmitted, showed an overall positive rate of 45% in subjects recovering from acute malaria infection. 8 Although approximately half the people exposed to malaria in areas where transmission is low and unstable have T cells that recognize CS epitopes, these previous studies focused on subjects exposed for short periods of time, ranging from a few months to a few years.…”

Cross‐reactive cellular immune response to circumsporozoite proteins of Plasmodium vivax and P. falciparum in malaria‐exposed individuals

“…In the non-immune population of Madagascar, where P. falciparum malaria reappeared after 20 years without active transmission, the proliferative response to CS protein of this parasite was positive in 35% of the individuals (Chougnet et al 1990). Similarly, seven of 22 (32%) individuals from malaria-endemic areas of Brazil had PBMC proliferative responses when stimulated with rPvCS (Rodrigues et al 1991).…”

“…Cross-reaction with proteins from the S. cerevisiae yeast, which expressed the CS proteins, is unlikely to explain this result since: (a) the SI D were corrected from the values obtained with yeast, used as a control antigen in each individual; (b) in 6 of the 11 individuals who responded to yeast extract, the cellular response was restricted to the yeast (data not shown). These proteins, produced and donated by Chiron Corporation (USA), have been used before in experiments of cellular proliferation, and it had been determined that reactivity was atrributed to the CS protein and not to the yeast extract (Rodrigues et al 1991).…”

Insights into the naturally acquired immune response toPlasmodium vivaxmalaria

“…The frequency of positive responders varied in all studies, likely reflecting the protein or peptide used for stimulation, the different assays employed, the transmission intensity in the region and the level of past exposure. The most extensively studied non-blood-stage protein is the circumsporozoite protein (CSP) (Rodrigues et al 1991; Herrera et al 1992; Bilsborough et al 1993; Migot et al 1993; Carvalho et al 1997; Suphavilai et al 2004; Seth et al 2010), however, the majority of these studies were conducted more than 10 years ago and hence cellular responses were assessed using immune assays that are now considered outdated. Nevertheless, the frequency of recognition of various P. vivax CSP epitopes varied from less than 20% in Thai individuals (Suphavilai et al 2004), to almost 60% in a region of the Colombian Pacific Coast (Herrera et al 1992) and in Caucasian volunteers who had previously lived for more than 7 years in a malaria endemic region (either PNG, the Solomon Islands or south-east Asia) (Bilsborough et al 1993).…”