Identificação, caracterização e determinação de padrões da resposta imune de epítopos imunogênicos de Plasmodium vivax

• Ano de defesa: 2023
• Autor(a) principal: Raianna Farhat Fantin
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; Brasil; MEDICINA - FACULDADE DE MEDICINA; Programa de Pós-Graduação em Ciências da Saúde - Infectologia e Medicina Tropical; UFMG
• Palavras-chave em Português: Malária; Plasmodium vivax; Imunidade Humoral; Epitopos; Dissertação Acadêmica
• Link de acesso: http://hdl.handle.net/1843/54177; https://orcid.org/0000-0003-0184-8612

Plasmodium vivax is a major challenge for malaria control due to its wide geographic distribution, high frequency of submicroscopic infections, and ability to induce relapses due to the latent forms present in the liver (hypnozoites). The recent increase in drug-resistant P. vivax strains, the evolution toward more virulent forms and the early production of gametocytes adds up to make P. vivax malaria a public health issue of increasing importance. Besides its tricky biological features and new awareness of its virulence, minimal investments have been made in vaccine discovery for P. vivax. Given that, this study aimed to discover and characterize potential new targets for future vaccine development using samples from different endemic areas around the world (Brazil, Mali, Cambodia and United States of America). For this purpose, we investigated and characterized a novel protein recently discovered in the urine of naturally infected subjects (PvVir14) and described the immunogenic potential of peptides from a well-known vivax protein (PvAMA-1), which has been proved to have important B cell epitopes that can induce specific immune response. Circulating antibodies against PvVir14 appeared in 61% and 34.5% of subjects from Brazil and Cambodia, respectively, versus none (0%) of the P. falciparum-infected subjects from Mali who have no exposure to P. vivax. PvVir14 antibody levels correlated with those against other well-characterized sporozoite/liver (PvCSP) and blood stage (PvDBP-RII) antigens, which were recognized by 7.6% and 42% of Brazilians, respectively. Concerning the cellular immune profiling of Brazilian subjects, PvVir14 seroreactive individuals displayed significantly higher levels of circulating atypical (CD21− CD27−) B cells, raising the possibility that atypical B cells may be contribute to the PvVir14 antibody response. Among T cells, CD4+ and CD8+ levels differed (lower and higher, respectively) between subjects with versus without antibodies to PvVir14, while NKT cell levels were higher in those without antibodies. As for PvAMA-1, the antigenicity of the selected B-cell peptides was assessed by multiple serological assays using sera from acute P.vivax infected subjects. The synthetic peptides were recognized by 45.5%, 48.7% and 32.2% of infected subjects for peptides I, II and III respectively. Moreover, when synthetized together (tripeptide), the reactivity increases up to 62%, which is comparable to the reactivity found against the whole protein PvAMA-1 (57%). Furthermore, IgG reactivity against the tripeptide after depletion was reduced by 42%, indicating that these epitopes may be responsible for a considerable part of the protein immunogenicity. These results represent an excellent perspective on discovering new targets with immunogenic potential to compose a vaccine, or even to assist the development of other control measures, such as diagnostic tools, since contemplating several targets seems to be the key to achieving a robust and protective response that a malaria vaccine needs to be successful.