Naturally Acquired Antibodies to Plasmodium vivax Duffy Binding Protein (DBP) in Rural Brazilian Amazon

Abstract

Abstract. Duffy binding protein (DBP), a leading malaria vaccine candidate, plays a critical role in Plasmodium vivax erythrocyte invasion. Sixty-eight of 366 (18.6%) subjects had IgG anti-DBP antibodies by enzyme-linked immunosorbent assay (ELISA) in a community-based cross-sectional survey in the Brazilian Amazon Basin. Despite continuous exposure to low-level malaria transmission, the overall seroprevalence decreased to 9.0% when the population was reexamined 12 months later. Antibodies from 16 of 50 (36.0%) subjects who were ELISA-positive at the baseline were able to inhibit erythrocyte binding to at least one of two DBP variants tested. Most (13 of 16) of these subjects still had inhibitory antibodies when reevaluated 12 months later. Cumulative exposure to malaria was the strongest predictor of DBP seropositivity identified by multiple logistic regression models in this population. The poor antibody recognition of DBP elicited by natural exposure to P. vivax in Amazonian populations represents a challenge to be addressed by vaccine development strategies.

Antibody Responses and Avidity of Naturally Acquired Anti-Plasmodium vivax Duffy Binding Protein (PvDBP) Antibodies in Individuals from an Area with Unstable Malaria Transmission

“…28,33 However, the serologic responses of residents in vivax malaria-endemic regions did show a positive correlation with exposure and host age, as shown in the previous studies. 23,28,30,44 This result suggests a possible boosting of the PvDBP-II antibody response because of accumulated age-related exposure. In addition, our present results showed that exposure and age represent key determinants of the quantitative nature of the IgG response to PvDBP-II.…”

“…Antibody responses to PvDBP have been shown in endemic populations of P. vivax infection in Papua New Guinea, [23][24][25] Brazil, [26][27][28] and Colombia. 29 In addition, different studies suggested that stronger humoral and cellular immune responses to PvDBP-II develop progressively with increasing age, 22,24,29,30 showing a boosting effect that was likely because of repeated exposures to the infection.…”

“…29 In addition, different studies suggested that stronger humoral and cellular immune responses to PvDBP-II develop progressively with increasing age, 22,24,29,30 showing a boosting effect that was likely because of repeated exposures to the infection. 28 Also, the anti-PvDBP-II antibodies in populations living in areas endemic for P. vivax could block PvDBP-II ligand DARC-positive erythrocytes 21,31 and inhibit erythrocyte invasion in vitro . 28,32 As shown by several studies, selection of an antigen for vaccination requires a detailed understanding of natural immune responses elicited by the protein from different malariaendemic regions with various epidemiology, and the result of similar studies from one malaria-endemic region cannot be extrapolated to other areas of malaria-endemic regions in the world.…”

“…28 Also, the anti-PvDBP-II antibodies in populations living in areas endemic for P. vivax could block PvDBP-II ligand DARC-positive erythrocytes 21,31 and inhibit erythrocyte invasion in vitro . 28,32 As shown by several studies, selection of an antigen for vaccination requires a detailed understanding of natural immune responses elicited by the protein from different malariaendemic regions with various epidemiology, and the result of similar studies from one malaria-endemic region cannot be extrapolated to other areas of malaria-endemic regions in the world. 33 Therefore, the current investigation was designed, Abstract.…”

Multiple interests in structural models of DARC transmembrane protein

“…Naturally acquired antibodies to DBP seem to confer protection from blood-stage P. vivax infection, supporting the development of a vaccine against P. vivax malaria [18]. However other studies also pinpointed that produced human antibodies might have low efficiencies underlining the difficulty of vaccine design [19]. Hence, alternative approaches to interfere with P. vivax merozoite with DARC on red cells are demanded.…”