Evaluation of Naturally Acquired Antibody Responses to Two Variant Forms of Plasmodium vivax Apical Membrane Antigen-1 in Individuals Living in Areas of Low and Unstable Malaria Transmission of Iran

Acquired antibody responses following natural infection provide valuable information for selection of candidate antigens for malaria vaccines. Apical membrane antigen-1 of Plasmodium vivax (PvAMA-1) has potential as a component of a subunit vaccine for vivax malaria. In addition, genetic diversity in this antigen is responsible for challenges in the development of an effective PvAMA-1 based vaccine. Therefore, the main aim of this study was to determine whether allelic polymorphisms in pvama-1 influence the recognition of naturally occurring antibodies. Also, the profile of IgG isotypes to two sequence types of PvAMA-1 antigen was evaluated among subjects exposed to P. vivax in areas of low and unstable transmission. For this purpose, the two variant forms of PvAMA-1 (PvAMA-1A and B) were expressed in Escherichia coli M15-pQE30 system using genomic DNA from Iranian individuals with patent P. vivax infection. Anti-AMA-1 response and isotype composition to two variant forms were measured in target P. vivax-infected individuals (n = 110, 2 to 65 years old) using Enzyme-linked immunosorbent assay. The results showed that 65.5% of the studied individuals had positive IgG responses to two PvAMA-1 variants, and the prevalence of responders did not differ significantly (P = 0.32). Also, a marked isotype switching to cytophilic (IgG1 /IgG3) antibodies was evident with increasing age, and adults responded more frequently to these antigens than did younger children. In conclusion, the presence of mature, protective isotype antibodies and equal immune responses to two genetically distinct variant forms of antigens in individuals from low transmission areas implicates that one of these forms could be used in a universal blood-stage vaccine based on PvAMA-1 antigen.