Longevity of naturally acquired antibody responses to the N- and C-terminal regions of Plasmodium vivax merozoite surface protein 1.

Abstract

Abstract. In an earlier study, we found that individuals with patent infection had significantly higher IgG antibody titers to the 19-kD C-terminal region of Plasmodium vivax merozoite surface protein 1 (PvMSP1) than individuals treated for malaria 1-4 months earlier. These results suggested that the antibody levels decreased rapidly following treatment. The present study was designed to determine the persistence of antibody response to the N-and C-terminal regions of PvMSP1 after infection with P. vivax in individuals from the city of Bélem in northern Brazil. Our results demonstrated that the vast majority of individuals had a significant decrease in antibody titers to the C-terminal region of PvMSP1 in a period of two months following treatment. Among responders to the C-terminal region, 44.4% became serologically negative and 44.4% had their antibody titers reduced by an average of 13-fold. Only 11.2% of the individuals had their antibody titers maintained or slightly increased during that period. A decrease in the antibody response to the recombinant protein representing the N-terminal region of PvMSP1 was also noted; however, it was not as dramatic. The rapid decrease in the antibody levels to the C-terminal region of PvMSP1 might contribute to the high risk of reinfection in these individuals.Plasmodium vivax is the second most prevalent species that causes malaria in humans and accounts for approximately 35 millions cases of the disease every year.1 In many countries, e.g., Brazil, P. vivax is the most common species, where it caused 76.8% of the 405,051 cases reported in 1997. 2 In spite of being highly prevalent in many parts of the world, the immunologic mechanisms operating in individuals exposed to P. vivax are poorly understood. We have characterized serum antibody and T cell reactivity of individuals from northern Brazil recently exposed to P. vivax malaria with 11 recombinant proteins representing the N-and Cterminal regions of the merozoite surface protein 1 of P. vivax (PvMSP1). 3 We found that a high frequency of individuals had IgG antibodies and T cell reactivity to at least one recombinant protein derived from PvMSP1. 3 The recombinant protein, which is based on the 19-kD C-terminal region of PvMSP1 (PvMSP1 19 ) containing the two epidermal growth factor (EGF)-like regions, was the most immunogenic during natural infection in humans. Antibodies or T cells of 83.8% of the individuals recognized this recombinant protein. 3 Furthermore, the antibody titers to the C-terminal region of PvMSP1 were higher than the titers to the N-terminal region. This high frequency of responders was also described in an independent survey performed in Papua New Guinea, where the sera of more than 80% of the individuals reacted with a recombinant protein representing PvMSP1 19 . 4 These immunoepidemiologic studies on naturally acquired immunity to the C-terminal of PvMSP1 are of particular importance since this region of MSP1 is being intensively studied as a candidate for development of a vaccine against malaria...

Cellular responses to Plasmodium falciparum major surface antigens and their relationship to human activities associated with malaria transmission.

“…18 The only other report concerning cellular responses to MSP-1 among Brazilians was to P.vivax. 28 The investigators used polypeptides representing the N-and C-terminal regions of the protein and showed PBMC stimulation ranging from 17% to 47% in the malaria-exposed group.…”

Disulfide bonds in merozoite surface protein 1 of the malaria parasite impede efficient antigen processing and affect the in vivo antibody response

“…High titers of MSP1 19 -specific antibody are required to achieve such protection [8,9]. In humans, natural infection generates MSP1 19 -specific antibodies, but these appear to be short-lived at least in children, and levels are generally not as high as to other parts of the MSP1 complex [10][11][12][13][14][15]. CD4 + T cell responses are essential for protective immunity in rodent models of malaria and in protective immunity induced by immunization with MSP1 19 [16].…”

Naturally acquired antibodies to merozoite surface protein (MSP)-1(19) and cumulative exposure to Plasmodium falciparum and Plasmodium vivax in remote populations of the Amazon Basin of Brazil

“…Contrasting with the extensive investigation of the role of Pf MSP-1 19 in naturally acquired immunity, little is known about the immune recognition of the ortholog protein of P. vivax (Pv). In Brazil, high proportions of subjects with detectable antibodies and T-cell responses to PvMSP-1 19 were found in areas of focal transmission (Soares et al 1997(Soares et al , 1999b and high proportions of seropositive subjects were uniformly observed in areas with more stable transmission (Morais et al 2005).…”