Abstract
In Brazil, Plasmodium vivax infection accounts for around 80% of malaria cases. This infection has a substantial impact on the productivity of the local population as the course of the disease is usually prolonged and the development of acquired immunity in endemic areas takes several years. The recent emergence of drug-resistant strains has intensified research on alternative control methods such as vaccines. There is currently no effective available vaccine against malaria; however, numerous candidates have been studied in the past several years. One of the leading candidates is apical membrane antigen 1 (AMA1). This protein is involved in the invasion of Apicomplexa parasites into host cells, participating in the formation of a moving junction. Understanding how the genetic diversity of an antigen influences the immune response is highly important for vaccine development. In this study, we analyzed the diversity of AMA1 from Brazilian P. vivax isolates and 19 haplotypes of P. vivax were found. Among those sequences, 33 nonsynonymous PvAMA1 amino acid sites were identified, whereas 20 of these sites were determined to be located in predicted B-cell epitopes. Nonsynonymous mutations were evaluated for their influence on the immune recognition of these antigens. Two distinct haplotypes, 5 and 16, were expressed and evaluated for reactivity in individuals from northern Brazil. Both PvAMA1 variants were reactive. Moreover, the IgG antibody response to these two PvAMA1 variants was analyzed in an exposed but noninfected population from a P. vivax endemic area. Interestingly, over 40% of this population had antibodies recognizing both variants. These results have implications for the design of a vaccine based on a polymorphic antigen.
Highlights
Malaria remains one of the greatest global public health problems, with approximately 3.3 billion people being at risk of infection
Plasmodium vivax is the most abundant Plasmodium species in Brazil. While this species has been neglected for many years, the recent emergence of drug-resistant strains and the absence of a vaccine intensified the efforts for a better control method
Acquired immune response analysis is a useful tool for understanding the antigenicity of Plasmodium proteins and evaluating the potential of a vaccine candidate
Summary
Malaria remains one of the greatest global public health problems, with approximately 3.3 billion people being at risk of infection. In South and Central America, P. vivax accounts for over 70% of malaria cases, thereby representing the most prevalent Plasmodium species. In Brazil, approximately 174,000 cases of vivax malaria were reported last year, which corresponds to 89.2% of the total number of malaria cases [1, 2]. P. vivax infection can be treated with chemotherapy; resistance is rising and alternative therapies are increasingly desirable [3]. No vaccines against vivax malaria are available to date. Several vaccine candidates have been studied [4, 5] Among these candidates, the leading antigen candidate for vivax malaria is apical membrane antigen 1 (AMA1)
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