Dados do Trabalho

Título

IDENTIFICATION AND VALIDATION OF GMZ2.6C IMMUNODOMINANT B-CELL EPITOPES IN INDIVUALS EXPOSED TO MALARIA LIVING IN BRAZILIAN ENDEMIC AREAS

Introdução

The GMZ2.6c malaria vaccine candidate is a multi-stage P. falciparum chimeric protein that contains a fragment of the sexual-stage Pfs48/45-6C protein genetically fused to GMZ2, an asexual-stage vaccine construction consisting of the N-terminal region of the Glutamate-Rich Protein (GLURP) and the C-terminal region of Merozoite Surface Protein-3 (MSP-3), presently in phase II clinical trial. Previous study showed that GMZ2.6c is widely recognized by antibodies from Brazilian exposed individuals and that its components are immunogenic in natural infection by P. falciparum. Also, anti-GMZ2.6c antibodies increase with exposure to malaria infection and may contribute to parasite immunity. Therefore, identify epitopes of proteins recognized by antibodies may be an important tool to understand the protective immunity.

Objetivo(s)

The present work aimed to identify and validate the immunodominant B-cell epitopes of GMZ2.6c chimeric protein in individuals exposed to malaria living in Brazilian Amazon.

Material e Métodos

The study was performed using serum samples from 303 individuals from Cruzeiro do Sul and Mâncio Lima, Acre State, and Guajará, Amazonas State. Specific IgG antibodies and subclasses against MSP-3, GLURP and Pfs48/45 B-cell epitopes were detected by Enzyme-Linked Immunosorbent Assay using synthetic peptides corresponding to B-cell epitopes previously described for MSP-3 (MSP-3a, MSP-3b, MSP-3c and DG210) and GLURP (P1, P2, P3, P4, P5, P6, P7, P8, P9, P10, P11, S2 and S3) or identified using BepiPred 1.0 for Pfs48/45 (Pfs48/45a and Pfs48/45b).

Resultados e Conclusão

The results showed that P11 (45%) from GLURP, and MSP-3c (48,2%) and DG210 (50%) from MSP-3 were preferentially recognized by antibodies from the studied population. Although at low frequency, responders to P1, P3, P4, S3, from GLURP, and MSP-3a and MSP-3b, from MSP-3 presented higher IgG antibody levels. The IgG1 and IgG3 subclasses were more frequent for all immunodominant epitopes, supporting previous studies that these proteins are targets of cytophilic antibodies, important for the acquisition of protective immunity. Most individuals (68,5%) presented detectable IgG antibodies against Pfs48/45a and/or Pfs48/45b, validating the prediction of linear B-cell epitopes. In conclusion, the higher frequency and antibody levels against different epitopes from GLURP, MSP-3 and Pfs48/45 highlights the relevance of GMZ2.6c as malaria vaccine candidate.

Palavras-chave

GMZ2.6c; Epitope mapping; Antibodies; Malaria; Plasmodium falciparum; Vaccine.