Plasmodium vivaxAMA1: Implications of distinct haplotypes for immune response

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Bittencourt, Najara Carneiro ^[1] ; Iung Enembreck da Silva, Ana Beatriz ^[2] ; Virgili, Natalia Silveira ^[1] ; Schappo, Ana Paula ^[2] ; Gervasio, Joao Henrique D. B. ^[2] ; Pimenta, Tamirys S. ^[3] ; Kujbida Junior, Mario A. ^[2] ; Ventura, Ana Maria R. S. ^[3] ; Libonati, Rosana M. F. ^[3] ; Silva-Filho, Joao Luiz ^[1] ; dos Santos, Hellen Geremias ^[2] ; Lopes, Stefanie C. P. ^{[4, 5]} ; Lacerda, Marcus V. G. ^{[4, 5]} ; Machado, Ricardo L. D. ^[6] ; Costa, Fabio T. M. ^[1] ; Albrecht, Letusa ^[2]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas UNICAMP, Inst Biol, Dept Genet Evolucao Microbiol & Imunol, Campinas, SP - Brazil

^[2] Fundacao Oswaldo Cruz FIOCRUZ, Inst Carlos Chagas, Curitiba, Parana - Brazil

^[3] Univ Fed Para, Nucleo Med Trop, Belem, Para - Brazil

^[4] Fundacao Med Trop Dr Heitor Vieira Dourado, Gerencia Malaria, Manaus, Amazonas - Brazil

^[5] FIOCRUZ AMAZONAS, Inst Leonidas & Maria Deane, Manaus, Amazonas - Brazil

^[6] Univ Fed Fluminense, Ctr Invest Microrganismos, Niteroi, RJ - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS Neglected Tropical Diseases; v. 14, n. 7 JUL 2020.
• Citações Web of Science: 0

Resumo

In Brazil,Plasmodium vivaxinfection 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 BrazilianP.vivaxisolates and 19 haplotypes ofP.vivaxwere 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 aP.vivaxendemic 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. Author summary Plasmodium vivaxis the most abundantPlasmodiumspecies 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. Naturally acquired immune response analysis is a useful tool for understanding the antigenicity ofPlasmodiumproteins and evaluating the potential of a vaccine candidate. In this study, the genetic variability of one of the leadingP.vivaxvaccine candidates (PvAMA1) was analyzed. Two distinct variants were expressed and the antibody response was evaluated in infected and noninfected individuals in the Brazilian Amazon. This improved understanding of the magnitude and dynamics of the antibody response will contribute to the knowledge of a vaccine candidate and open new perspectives in vivax malaria vaccine development. (AU)

• Processo FAPESP: 16/12855-9 - Mecanismo de ação da lipoxina na proteção do desenvolvimento da malária cerebral experimental
• Beneficiário: João Luiz da Silva Filho
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 15/02808-0 - Análise da diversidade genética e imunogenicidade da proteína MAEBL de Plasmodium vivax
• Beneficiário: Najara Carneiro Bittencourt
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 12/16525-2 - Plasmodium vivax: patogênese e infectividade
• Beneficiário: Fabio Trindade Maranhão Costa
• Modalidade de apoio: Auxílio à Pesquisa - Temático