University of Hawaii, School of Medicine, Department of Tropical Medicine, Honolulu, Hawaii, United States of America.
PLoS One. 2013 Sep 30;8(9):e75939. doi: 10.1371/journal.pone.0075939. eCollection 2013.
The P. falciparum Merozoite Surface Protein 1-42 (MSP1-42) is one of the most studied malaria subunit vaccine candidates. The N-terminal fragment of MSP1-42, MSP1-33, is primarily composed of allelic sequences, and has been shown to possess T helper epitopes that influence protective antibody responses toward the C-terminal region, MSP1-19. A truncated MSP1-42 vaccine, Construct 33-I, consisting of exclusively conserved T epitope regions of MSP1-33 expressed in tandem with MSP1-19, was previously shown to be a more effective immunogen than the full-length MSP1-42 vaccine. Here, by way of reciprocal priming/boosting immunization regimens, we studied the immunogenicity of Construct 33-I in the context of recognition by immune responses induced by the full-length native MSP1-42 protein, in order to gauge the effects of pre- and post-exposures to MSP1-42 on vaccine induced responses. Judging by immune responsiveness, antibody and T cell responses, Construct 33-I was effective as the priming antigen followed by full-length MSP1-42 boosting, as well as the boosting antigen following full-length MSP1-42 priming. In particular, Construct 33-I priming elicited the broadest responsiveness in immunized animals subsequently exposed to MSP1-42. Moreover, Construct 33-I, with its conserved MSP1-33 specific T cell epitopes, was equally well recognized by homologous and heterologous allelic forms of MSP1-42. Serum antibodies raised against Construct 33-I efficiently inhibited the growth of parasites carrying the heterologous MSP1-42 allele. These results suggest that Construct 33-I maintains and/or enhances its immunogenicity in an allelic or strain transcending fashion when deployed in populations having prior or subsequent exposures to native MSP1-42s.
恶性疟原虫裂殖子表面蛋白 1-42（MSP1-42）是研究最多的疟疾亚单位疫苗候选物之一。MSP1-42 的 N 端片段，MSP1-33，主要由等位基因序列组成，已显示具有 T 辅助表位，影响针对 C 端区域 MSP1-19 的保护性抗体反应。一种截断的 MSP1-42 疫苗，构建体 33-I，由 MSP1-33 的完全保守的 T 表位区域串联 MSP1-19 组成，先前已显示比全长 MSP1-42 疫苗更有效。在这里，通过相互 priming/boosting 免疫方案，我们研究了在全长天然 MSP1-42 蛋白诱导的免疫反应识别背景下，构建体 33-I 的免疫原性，以评估 MSP1-42 暴露前和暴露后对疫苗诱导反应的影响。根据免疫反应性、抗体和 T 细胞反应，构建体 33-I 作为 priming 抗原随后进行全长 MSP1-42 增强，以及全长 MSP1-42 作为 priming 抗原随后进行全长 MSP1-42 增强是有效的。特别是，构建体 33-I 作为 priming 抗原在随后暴露于 MSP1-42 的免疫动物中引起了最广泛的反应性。此外，构建体 33-I 具有其保守的 MSP1-33 特异性 T 细胞表位，同样可以被同源和异源等位基因形式的 MSP1-42 识别。针对构建体 33-I 产生的血清抗体有效地抑制了携带异源 MSP1-42 等位基因的寄生虫的生长。这些结果表明，当在先前或随后暴露于天然 MSP1-42 的人群中部署时，构建体 33-I 以等位基因或菌株超越的方式保持和/或增强其免疫原性。
