Dados do Trabalho

Título

T-cell epitope mapping of the Plasmodium falciparum malaria vaccine candidate GMZ2.6c in a naturally exposed population of the Brazilian Amazon

Introdução

The GMZ2.6c malaria vaccine candidate is a multi-stage Plasmodium 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). Previous study showed that GMZ2.6c is widely recognized by antibodies and T cells 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 T cells may be an important tool to understand the protective immunity.

Objetivo (s)

Herein, we identify and validate T-cell epitopes of GMZ2.6c chimeric protein in individuals exposed to malaria living in Brazilian Amazon.

Material e Métodos

The study was carried out using peripheral blood mononuclear cells of individuals from Cruzeiro do Sul and Mâncio Lima, Acre state, and Guajará, Amazonas state. Potential T-cell epitopes of GLURP-R0, MSP-3-C-terminal and Pfs48/45-6c were predicted using the Immune Epitope DataBase (IEDB). The relative number of specific IFN-γ-secreting T cells against pools containing synthetic peptides for MSP-3 (Mpp I), GLURP (Gpp I) and Pfs48/45 (Ppp I and Ppp II) was performed by ELISpot assay.

Resultados e Conclusão

Twelve sequences with average consensus scores less than 20% and at least 50% HLA binding frequency were identified as potential T-cell epitopes and grouped into four pools for validation by ELISpot assay. All the four pools induced IFN-γ T-cells response in a naturally exposed population of Brazilian Amazon, validating the prediction of T-cell epitopes. Individuals infected by P. falciparum showed a higher frequency of responders against Mpp I and a lower frequency of responders against Ppp I than non-infected individuals. Interestingly, non-infected individuals responding to the Mpp I and Gpp I pools had longer time since last malaria infection than non-responding individuals. In conclusion, we identified multiple T-cell epitopes derived from GLURP, MSP-3 and Pfs48/45 widely recognized by T cells from residents of the studied endemic areas that may contribute to antiparasitic immunity, highlighting the importance of GMZ2.6c as a multistage vaccine candidate.

Palavras-chave

GMZ2.6c, Epitope mapping, T cells, P. falciparum, Vaccine.

Agradecimentos

FIOCRUZ, CAPES, CNPq and FAPERJ.