A Reduced Risk of Infection with Plasmodium vivax and Clinical Protection against Malaria Are Associated with Antibodies against the N Terminus but Not the C Terminus of Merozoite Surface Protein 1

Abstract

Progress towards the development of a malaria vaccine against Plasmodium vivax, the most widely distributed human malaria parasite, will require a better understanding of the immune responses that confer clinical protection to patients in regions where malaria is endemic. The occurrence of clinical protection in P. vivax malaria in Brazil was first reported among residents of the riverine community of Portuchuelo, in Rondônia, western Amazon. We thus analyzed immune sera from this same human population to determine if naturally acquired humoral immune responses against the merozoite surface protein 1 of P. vivax, PvMSP1, could be associated with reduced risk of infection and/or clinical protection. Our results demonstrated that this association could be established with anti-PvMSP1 antibodies predominantly of the immunoglobulin G3 subclass directed against the N terminus but not against the C terminus, in spite of the latter being more immunogenic and capable of natural boosting. This is the first report of a prospective study of P. vivax malaria demonstrating an association of reduced risk of infection and clinical protection with antibodies against an antigen of this parasite.Malaria remains one of the major public health problems in South and Central America, where Plasmodium vivax is the main species responsible for infections. Although malaria caused by this human parasite is not lethal, the clinical manifestations represent a major socioeconomical burden in the major cities and rural areas of the Brazilian Amazon, which contains 99.7% of all malaria cases. Although a few studies indicate that some cross-protection between Plasmodium vivax, the most widely distributed human malaria parasite, and P. falciparum, the most virulent species, does occur (33), immunity in malaria is mostly species specific; thus, it is likely that a vaccine against P. falciparum will not cross-protect against P. vivax. Progress is being made to develop P. vivax vaccines per se (for a review, see reference 2); however, to date there are no prospective studies associating human immune responses to any P. vivax antigen with clinical protection.The history of malaria in Brazil has been punctuated with epidemics associated with migration movements of nonimmune population to areas where malaria is endemic (20,30,36). Previous studies done in these epidemiological settings showed that Plasmodium infection was always associated with symptoms, and clinical protection was not observed (27). However, through a cross-sectional and longitudinal study among native Amazon residents of the riverine community of Portuchuelo in Rondônia, located in the western Brazilian Amazon, the occurrence of symptomless Plasmodium vivax-infected individuals was reported (1, 6). Symptomless Plasmodium infections were defined as individuals who contain parasites in their peripheral blood, as detected by Giemsa blood smears and/or PCR, and who were not drug treated yet did not develop clinical symptoms during a 2-month individual follow-up. These rigorous criteria...

Molecular markers and genetic diversity of Plasmodium vivax

“…The 200-kDa MSP 1 in P. vivax (PvMSP-1), originally described at the molecular level by del Portillo et al (1991), is a major target of naturally acquired (Nogueira et al 2006) and vaccine-induced immunity (Yang et al 1999, Herrera et al 2007). The protein contains six highly polymorphic domains (4 of them repetitive) flanked by seven fairly conserved sequences (Putaporntip et al 2002) (Fig.…”

Immunological markers of Plasmodium vivax exposure and immunity: a systematic review and meta-analysis

“…The full texts of these 162 studies were examined to determine whether they complied with eligibility criteria: 114 did not meet the inclusion criteria (see Additional file 3), 7 fulfilled the inclusion and quality criteria (Figure 1), and 41 studies potentially met inclusion and quality criteria. The authors of the 41 studies that potentially met inclusion and quality criteria were contacted, yielding a further 11 studies that met inclusion and quality criteria, providing a total of 18 studies that were included in the review [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] (Figure 1). Details of these 18 studies are shown in Table 1.…”

Polymorphism of the Pv200L Fragment of Merozoite Surface Protein-1 of Plasmodium vivax in Clinical Isolates from the Pacific Coast of Colombia

“…7 Second, it has been demonstrated that naturally acquired IgG antibodies directed to the N-terminal region of Pv MSP-1 are associated with clinical protection to P. vivaxmalaria. 25 Third, previously defined promiscuous T-helper epitopes are located at highly conserved portions of Pv 200L and displayed a high conservation pattern across the 68 sequences of Pv 200L. This is the first study of Pv 200L polymorphism in Colombia.…”