Acquired immune responses to the N- and C-terminal regions of Plasmodium vivax merozoite surface protein 1 in individuals exposed to malaria

Abstract

In this study, we evaluated the naturally acquired immune response to Plasmodium vivax merozoite surface protein 1 (PvMSP1) in individuals with recent clinical episodes of malaria from the state of Pará, Brazil. Ten recombinant proteins representing the first 682 amino acids (aa) of the N-terminal region and one representing the final 111 aa of the C-terminal region were expressed in Escherichia coli as glutathione S-transferase fusion proteins. Both of these regions have been suggested as candidates for development of a vaccine against Plasmodium sp. The total frequencies of individuals with antibodies and cellular immune responses to PvMSP1 were high (83.8 and 75%, respectively). The recombinant proteins representing the N-and C-terminal regions were recognized by 51.4 and 64.1% of sera, respectively. The frequency of responders to the C-terminal region increased according to the number of previous malaria episodes, reaching 83.3% after four episodes. Cellular immune response was measured by in vitro proliferation and gamma interferon production. Peripheral blood mononuclear cells of 75 and 47.2% of individuals proliferated in response to stimulation by the N-and C-terminal regions, respectively. Also, we found that one protein representing the N terminus and a second representing the C terminus of PvMSP1 stimulated 54.5% of individuals to secrete gamma interferon. We concluded that PvMSP1 is immunogenic to a large proportion of individuals exposed to malaria. Our results also suggested that the C-terminal region of PvMSP1 containing the two epidermal growth factor-like domains is particularly immunogenic to antibodies and T cells during natural infection in humans.

Chagasic patients develop a type 1 immune response to Trypanosoma cruzi trans‐sialidase

“…Plasmas or cells from individuals were tested for reactivity with the native or recombinant TS by proliferation assay and ELISA essentially as described by Soares et al (1997). For the proliferation assay, arithmetic mean cpm for each set of triplicate wells was calculated.…”

Recombinant Mycobacterium bovis Bacillus Calmette-Guérin Secreting Merozoite Surface Protein 1 (MSP1) Induces Protection against Rodent Malaria Parasite Infection Depending on MSP1-stimulated Interferon γ and Parasite-specific Antibodies

“…The isotype content of sera from individuals with defined clinical states of resistance or susceptibility to malaria has been investigated in several tropical countries. Those studies also revealed that the cytophilic antibody subclasses predominated in protected subjects (63)(64)(65). It has also been reported that the antibody was necessary to eliminate a blood-stage malaria parasite infection (66).…”

Structure of a Fab Complex with the C-terminal fragment of merozoite surface protein-1 of Plasmodium vivax determined by Computational Docking

“…Homologue PvMSP1 a 200 kDa protein expressed on the surface of P. vivax merozoite, is also a current vaccine candidate against asexual blood stages [17]. Studies on the naturally acquired humoral immune responses against P. vivax MSP1, showed that MSP1 C-terminal fragment of P. vivax (PvMSP1 19 ) is the most immunogenic portion of the molecule and evidence suggests that immunodominant domains interacting with protective antibodies are related to a structure also containing two epidermal growth factor (EGF)-like domains, like in PfMSP1 19 [18,19]. Furthermore, vaccine trials with PvMSP1 19 and PvMSP1 33 have succeeded in protecting monkeys and it has been shown that a large proportion of individuals naturally exposed to P. vivax transmission, develop specific antibodies to PvMSP1 19 [20][21][22].…”