B-Cell Epitope Mapping of the Plasmodium falciparum Malaria Vaccine Candidate GMZ2.6c in a Naturally Exposed Population of the Brazilian Amazon

Abstract

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 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 Pfs48/45. 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 Pfs48/45a and/or Pfs48/45b, validating the prediction of linear B-cell epitopes. The higher frequency and antibody levels against different epitopes from GLURP, MSP-3, and Pfs48/45 provide additional information that may suggest the relevance of GMZ2.6c as a multi-stage malaria vaccine candidate.

Identification of B-Cell Linear Epitopes in the Nucleocapsid (N) Protein B-Cell Linear Epitopes Conserved among the Main SARS-CoV-2 Variants

“…Here, we predicted five B-cell linear epitopes in the SARS-CoV-2 N protein (N (34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48) , N (89-104) , N (185-197) , N (277-287) , and N (378-390) ) and confirmed their natural immunogenicity based on their recognition by samples from Brazilian COVID-19 convalescent donors. These data are in agreement with previous studies of our group in which we experimentally validated more than 80% of predicted epitopes from viruses [51,52], bacteria [53,54], and protozoa [55,56]. Moreover, our data corroborate previous studies that suggested similar regions as targets of antibodies [4,50,57,58].…”

Vaccine Development against Infectious Diseases: State of the Art, New Insights, and Future Directions

“…In Malaria research, the B-Cell epitope mapping of the Plasmodium falciparum malaria vaccine candidate GMZ2.6c offers valuable insights into the development of immunity against this deadly disease. By identifying the key epitopes recognized by antibodies, researchers aim to bolster our understanding of protective immunity [6].…”