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, Rodrigues-da-Silva Rodrigo Nunes, Riccio Evelyn Kety Pratt, Totino Paulo Renato Rivas, Lima-Junior Josué da Costa, Daniel-Ribeiro Cláudio Tadeu, Pratt-Riccio Lilian Rose
Laboratório de Pesquisa em Malária, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro 21040-900, RJ, Brazil.
Centro de Pesquisa, Diagnóstico e Treinamento em Malária (CPD-Mal), Fiocruz e Secretaria de Vigilância em Saúde, Ministério da Saúde, Rio de Janeiro 21040-900, RJ, Brazil.
Vaccines (Basel). 2023 Feb 15;11(2):446. doi: 10.3390/vaccines11020446.
The GMZ2.6c malaria vaccine candidate is a multi-stage chimeric protein that contains a fragment of the sexual-stage s48/45-6C 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 . 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 /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 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 s48/45a and/or s48/45b, validating the prediction of linear B-cell epitopes. The higher frequency and antibody levels against different epitopes from GLURP, MSP-3, and s48/45 provide additional information that may suggest the relevance of GMZ2.6c as a multi-stage malaria vaccine candidate.
GMZ2.6c疟疾候选疫苗是一种多阶段嵌合蛋白，它包含性阶段s48/45 - 6C蛋白的一个片段，该片段与GMZ2基因融合，GMZ2是一种无性阶段疫苗构建体，由富含谷氨酸蛋白（GLURP）的N端区域和裂殖子表面蛋白-3（MSP-3）的C端区域组成。先前的研究表明，GMZ2.6c被巴西暴露个体的抗体广泛识别，并且其成分在自然感染中具有免疫原性。此外，抗GMZ2.6c抗体随着感染暴露而增加，可能有助于寄生虫免疫。因此，鉴定被抗体识别的蛋白质表位可能是理解保护性免疫的重要工具。在此，我们鉴定并验证了GMZ2.6c的B细胞表位在生活于巴西亚马逊流行地区的疟疾暴露个体中具有免疫原性和免疫显性。使用对应于先前描述的MSP-3和GLURP的B细胞表位或通过BepiPred鉴定的s48/45的合成肽，通过ELISA检测针对MSP-3、GLURP和/45表位的特异性IgG抗体及其亚类。结果表明，免疫显性表位是来自GLURP的P11、MSP-3c以及来自MSP-3的DG210。IgG1和IgG3亚类优先针对这些表位被诱导产生，这支持了先前的研究，即这些蛋白质是嗜细胞性抗体的靶点，对获得保护性免疫很重要。大多数个体呈现出可检测到的针对s48/45a和/或s48/45b的IgG抗体，验证了线性B细胞表位的预测。针对GLURP、MSP-3和s48/45不同表位的较高频率和抗体水平提供了额外信息，这可能表明GMZ2.6c作为多阶段疟疾候选疫苗的相关性。
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