Ntumngia Francis B, Barnes Samantha J, McHenry Amy M, George Miriam T, Schloegel Jesse, Adams John H
Global Health Infectious Disease Research Program, Department of Global Health, University of South Florida, Tampa, Florida, USA.
Global Health Infectious Disease Research Program, Department of Global Health, University of South Florida, Tampa, Florida, USA
Clin Vaccine Immunol. 2014 Sep;21(9):1215-23. doi: 10.1128/CVI.00205-14. Epub 2014 Jun 25.
Molecules that play a role in Plasmodium merozoite invasion of host red blood cells represent attractive targets for blood-stage vaccine development against malaria. In Plasmodium vivax, merozoite invasion of reticulocytes is mediated by the Duffy binding protein (DBP), which interacts with its cognate receptor, the Duffy antigen receptor for chemokines, on the surface of reticulocytes. The DBP ligand domain, known as region II (DBPII), contains the critical residues for receptor recognition, making it a prime target for vaccine development against blood-stage vivax malaria. In natural infections, DBP is weakly immunogenic and DBPII allelic variation is associated with strain-specific immunity, which may compromise vaccine efficacy. In a previous study, a synthetic vaccine termed DEKnull that lacked an immunodominant variant epitope in DBPII induced functional antibodies to shared neutralizing epitopes on the native Sal1 allele. Anti-DEKnull antibody titers were lower than anti-Sal1 titers but produced more consistent, strain-transcending anti-DBPII inhibitory responses. In this study, we further characterized the immunogenicity of DEKnull, finding that immunization with recombinant DEKnull produced an immune response comparable to that obtained with native recombinant DBP alleles. Further investigation of DEKnull is necessary to enhance its immunogenicity and broaden its specificity.
在疟原虫裂殖子入侵宿主红细胞过程中发挥作用的分子，是开发抗疟疾血液期疫苗的有吸引力的靶点。在间日疟原虫中，裂殖子对网织红细胞的入侵由达菲结合蛋白（DBP）介导，该蛋白与网织红细胞表面的同源受体——趋化因子达菲抗原受体相互作用。DBP配体结构域，即区域II（DBPII），包含受体识别的关键残基，使其成为开发抗血液期间日疟疫苗的主要靶点。在自然感染中，DBP免疫原性较弱，且DBPII等位基因变异与菌株特异性免疫相关，这可能会影响疫苗效力。在之前的一项研究中，一种名为DEKnull的合成疫苗在DBPII中缺乏免疫显性变异表位，可诱导产生针对天然Sal1等位基因上共享中和表位的功能性抗体。抗DEKnull抗体滴度低于抗Sal1抗体滴度，但产生了更一致的、跨越菌株的抗DBPII抑制反应。在本研究中，我们进一步表征了DEKnull的免疫原性，发现用重组DEKnull免疫产生的免疫反应与用天然重组DBP等位基因获得的免疫反应相当。有必要对DEKnull进行进一步研究，以增强其免疫原性并拓宽其特异性。
