Evaluation of BALB/c Mice Antibody Responses to Two Variant Forms of Plasmodium vivax Apical Membrane Antigen-1 Recombinant Protein as a Malaria Vaccine Candidate

Authors
1 Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
2 Malaria and Vector Research Group (MVRG), Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
Abstract
Objective: Apical membrane antigen-1 (AMA-1) is one of the most promising blood-stage candidate antigens for production of a malaria vaccine against the Plasmodium parasite. Genetic diversity in protective antigens, which is a common phenomenon in a complex pathogen such as the Plasmodium parasite, is responsible for problems with the development of an effective malaria vaccine. This phenomenon will increase the parasite’s ability to evade immune responses. Therefore, malaria vaccine development requires the evaluation of immune responses to different allelic forms of the vaccine candidate antigens.
Methods: In this investigation, the two variant forms of PvAMA-1 (PvAMA-1A and B) were expressed in an Escherichia coli M15-pQE30 system using genomic DNA from Iranian individuals with patent Plasmodium vivax infection. The IgG responses of two antigens were evaluated in BALB/c mice with the purified protein emulsified in Freund's adjuvant. In addition, the correct conformation of the recombinant proteins was evaluated by the indirect immunofluorescence antibody test (IFA).
Results: The evaluation of immunogenic responses of two variant forms of PvAMA-1 showed the presence of IgG responses in mice after three immunizations. Cross-reactions were observed. Monitoring of IgG responses showed the persistence up to one year after the last immunization. The antibodies raised against recombinant PvAMA-1s in injected mice recognized the native protein (PvAMA-1) localized on Plasmodium vivax merozoites.
Conclusion: The present outcomes confirmed the presence of common epitopes in recombinant forms of the protein that corresponded to native proteins. These emulsified proteins in Freund's adjuvant were immunogenic in BALB/c mice and IgG responses persisted for up to one year. The IgG responses to two PvAMA-1 variants did not differ significantly. The presence of cross-reactive antibodies has implied that one of these two forms of protein could be used in a universal blood-stage vaccine based on the PvAMA-1 antigen.

Keywords


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