Article
B-Cell Epitope Mapping of the Plasmodium falciparum Malaria Vaccine Candidate GMZ2.6c in a Naturally Exposed Population of the Brazilian Amazon
Registro en:
BAPTISTA, Barbara de Oliveira et al. B-Cell Epitope Mapping of the Plasmodium falciparum Malaria Vaccine Candidate GMZ2.6c in a Naturally Exposed Population of the Brazilian Amazon. Vaccines, v.11, 446, p. 1 - 17, Feb. 2023.
2076-393X
10.3390/vaccines11020446
Autor
Baptista, Barbara de Oliveira
Souza, Ana Beatriz Lopes de
Oliveira, Luana Santos de
Souza, Hugo Amorim dos Santos de
Barros, Jenifer Peixoto de
Queiroz, Lucas Tavares de
Souza, Rodrigo Medeiros de
Amoah, Linda Eva
Singh, Susheel Kumar
Theisen, Michael
Silva, Rodrigo Nunes Rodrigues da
Riccio, Evelyn Kety Pratt
Totino, Paulo Renato Rivas
LIma Junior, Josué da Costa
Ribeiro, Cláudio Tadeu Daniel
Pratt-Riccio, Lilian Rose
Resumen
The GMZ2.6c malaria vaccine candidate is a multi-stage P. falciparum chimeric protein that
contains a fragment of the sexual-stage Pf s48/45-6C protein genetically fused to GMZ2, an asexualstage
vaccine construction consisting of the N-terminal region of the glutamate-rich protein (GLURP)
and the C-terminal region of the merozoite surface protein-3 (MSP-3). Previous studies 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. In addition, anti-GMZ2.6c antibodies
increase with exposure to infection and may contribute to parasite immunity. Therefore, identifying
epitopes of proteins recognized by antibodies may be an important tool for understanding protective
immunity. Herein, we identify and validate the B-cell epitopes of GMZ2.6c as immunogenic and
immunodominant in individuals exposed to malaria living in endemic areas of the Brazilian Amazon.
Specific IgG antibodies and subclasses against MSP-3, GLURP, and Pfs48/45 epitopes were detected
by ELISA using synthetic peptides corresponding to B-cell epitopes previously described for MSP-3
and GLURP or identified by BepiPred for Pf s48/45. The results showed that the immunodominant
epitopes were P11 from GLURP and MSP-3c and DG210 from MSP-3. The IgG1 and IgG3 subclasses
were preferentially induced against these epitopes, supporting previous studies that these proteins
are targets for cytophilic antibodies, important for the acquisition of protective immunity. Most
individuals presented detectable IgG antibodies against Pf s48/45a and/or Pf s48/45b, validating
the prediction of linear B-cell epitopes. The higher frequency and antibody levels against different
epitopes from GLURP, MSP-3, and Pf s48/45 provide additional information that may suggest the
relevance of GMZ2.6c as a multi-stage malaria vaccine candidate.