Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, China.
Department of Clinical Laboratory Medicine, Affiliated Hospital of Inner Mongolian Medical University, Hohhot, China.
Front Cell Infect Microbiol. 2024 Aug 27;14:1451063. doi: 10.3389/fcimb.2024.1451063. eCollection 2024.
Transmission-blocking vaccines (TBVs) can effectively prevent the community's spread of malaria by targeting the antigens of mosquito sexual stage parasites. At present, only a few candidate antigens have demonstrated transmission-blocking activity (TBA) potential in . Quiescin-sulfhydryl oxidase (QSOX) is a sexual stage protein in the rodent malaria parasite and is associated with a critical role in protein folding by introducing disulfides into unfolded reduced proteins. Here, we reported the immunogenicity and transmission-blocking potency of the PvQSOX in .
The full-length recombinant PvQSOX protein (rPvQSOX) was expressed in the expression system. The anti-rPvQSOX antibodies were generated following immunization with the rPvQSOX in rabbits. A parasite integration of the gene into the gene knockout genome was developed to express full-length PvQSOX protein in (Pv-Tr-PbQSOX). In western blot, the anti-rPvQSOX antibodies recognized the native PvQSOX protein expressed in transgenic gametocyte and ookinete. In indirect immunofluorescence assays, the fluorescence signal was detected in the sexual stages, including gametocyte, gamete, zygote, and ookinete. Anti-rPvQSOX IgGs obviously inhibited the ookinetes and oocysts development both and using transgenic parasites. Direct membrane feeding assays of anti-rPvQSOX antibodies were conducted using four field isolates (named isolates #1-4) in Thailand. Oocyst density in mosquitoes was significantly reduced by 32.00, 85.96, 43.52, and 66.03% with rabbit anti-rPvQSOX antibodies, respectively. The anti-rPvQSOX antibodies also showed a modest reduction of infection prevalence by 15, 15, 20, and 22.22%, respectively, as compared to the control, while the effect was insignificant. The variation in the DMFA results may be unrelated to the genetic polymorphisms. Compared to the Salvador (Sal) I strain sequences, the in isolate #1 showed no amino acid substitution, whereas isolates #2, #3, and #4 all had the M361I substitution.
Our results suggest that PvQSOX could serve as a potential TBVs candidate, which warrants further evaluation and optimization.
传播阻断疫苗（TBV）可以通过靶向蚊媒性阶段寄生虫的抗原，有效防止疟疾在社区中的传播。目前，只有少数候选抗原在 中表现出传播阻断活性（TBA）潜力。静止硫氧还蛋白氧化酶（QSOX）是啮齿动物疟原虫 的性阶段蛋白，与将二硫键引入未折叠的还原蛋白中对蛋白质折叠至关重要。在这里，我们报道了 中的 PvQSOX 的免疫原性和传播阻断效力。
全长重组 PvQSOX 蛋白（rPvQSOX）在 表达系统中表达。用 rPvQSOX 免疫兔子产生抗 rPvQSOX 抗体。开发了一种寄生虫整合 基因到 基因敲除基因组的方法，以在 （Pv-Tr-PbQSOX）中表达全长 PvQSOX 蛋白。在 Western blot 中，抗 rPvQSOX 抗体识别在转基因配子体和动合子中表达的天然 PvQSOX 蛋白。在间接免疫荧光检测中，荧光信号在性阶段包括配子体、配子、合子和动合子中被检测到。抗 rPvQSOX IgG 明显抑制了转基因寄生虫的动合子和卵囊发育。在泰国，用四种田间分离株（命名为分离株 #1-4）进行了抗 rPvQSOX 抗体的直接膜喂养试验。用兔抗 rPvQSOX 抗体处理后，蚊子中的卵囊密度分别降低了 32.00%、85.96%、43.52%和 66.03%。抗 rPvQSOX 抗体也使感染率分别降低了 15%、15%、20%和 22.22%，与对照组相比，效果不显著。DMFA 结果的差异可能与遗传多态性无关。与萨尔瓦多（Sal）I 株序列相比，分离株 #1 中的 没有氨基酸取代，而分离株 #2、#3 和 #4 都有 M361I 取代。
我们的结果表明，PvQSOX 可以作为一种潜在的 TBV 候选物，值得进一步评估和优化。
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