Anti-TRAP/SSP2 monoclonal antibodies can inhibit sporozoite infection and may enhance protection of anti-CSP monoclonal antibodies.
Anti-TRAP/SSP2 monoclonal antibodies can inhibit sporozoite infection and may enhance protection of anti-CSP monoclonal antibodies.
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DOI：
10.1038/s41541-022-00480-2
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发表时间：
2022-05-26
期刊：
影响因子：
9.2
通讯作者：
中科院分区：
文献类型：
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疫苗诱导的绝育保护免受导致疟疾的病原体疟原虫的感染，这将是防治疟疾的关键，因为它将防止疟疾相关疾病和传播。在蚊子注入的寄生虫从皮肤迁移到肝脏之前，阻止它们的数量相对较少，是实现这一目标的一个有吸引力的手段。为了达到这一目标，已经使用了抗体诱导疫苗，通过靶向这一阶段存在的主要寄生虫表面蛋白-环子孢子蛋白(CSP)。虽然基于CSP的疫苗最近在减少疾病方面取得了令人鼓舞的成功，但这只是在抗体效价极高的情况下实现的，对于完全阻断感染(即无菌保护)似乎效果较差。虽然这种疾病的减少很重要，但这些和其他结果表明，仅侧重于CSP的战略可能无法实现根除疟疾所需的高水平无菌保护。在这里，我们展示了识别另一种子孢子蛋白TRAP/SSP2的单抗表现出一系列的抑制活性，并且这些单抗可以增强基于CSP的保护，尽管它们本身没有提供无菌保护。因此，寻求多价亚单位疫苗免疫是改进阻断感染的疟疾疫苗的一个很有前途的策略。
Vaccine-induced sterilizing protection from infection by Plasmodium parasites, the pathogens that cause malaria, will be essential in the fight against malaria as it would prevent both malaria-related disease and transmission. Stopping the relatively small number of parasites injected by the mosquito before they can migrate from the skin to the liver is an attractive means to this goal. Antibody-eliciting vaccines have been used to pursue this objective by targeting the major parasite surface protein present during this stage, the circumsporozoite protein (CSP). While CSP-based vaccines have recently had encouraging success in disease reduction, this was only achieved with extremely high antibody titers and appeared less effective for a complete block of infection (i.e., sterile protection). While such disease reduction is important, these and other results indicate that strategies focusing on CSP alone may not achieve the high levels of sterile protection needed for malaria eradication. Here, we show that monoclonal antibodies (mAbs) recognizing another sporozoite protein, TRAP/SSP2, exhibit a range of inhibitory activity and that these mAbs may augment CSP-based protection despite conferring no sterile protection on their own. Therefore, pursuing a multivalent subunit vaccine immunization is a promising strategy for improving infection-blocking malaria vaccines.
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