与环子孢子蛋白一起进行红细胞前期抗原共免疫可增强针对子孢子感染的无菌保护。

Coimmunization with Preerythrocytic Antigens alongside Circumsporozoite Protein Can Enhance Sterile Protection against Sporozoite Infection.

作者信息

Vigdorovich Vladimir, Patel Hardik, Watson Alexander, Raappana Andrew, Reynolds Laura, Selman William, Beeman Suzannah, Edlefsen Paul T, Kappe Stefan H I, Sather D Noah

机构信息

Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, Washington, USA.

Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

出版信息

Microbiol Spectr. 2023 Feb 27;11(2):e0379122. doi: 10.1128/spectrum.03791-22.

Abstract

Malaria-causing parasites have a complex life cycle and present numerous antigen targets that may contribute to protective immune responses. The currently recommended vaccine-RTS,S-functions by targeting the Plasmodium falciparum circumsporozoite protein (CSP), which is the most abundant surface protein of the sporozoite form responsible for initiating infection of the human host. Despite showing only moderate efficacy, RTS,S has established a strong foundation for the development of next-generation subunit vaccines. Our previous work characterizing the sporozoite surface proteome identified additional non-CSP antigens that may be useful as immunogens individually or in combination with CSP. In this study, we examined eight such antigens using the rodent malaria parasite Plasmodium yoelii as a model system. We demonstrate that despite conferring weak protection individually, coimmunizing each of several of these antigens alongside CSP could significantly enhance the sterile protection achieved by CSP immunization alone. Thus, our work provides compelling evidence that a multiantigen preerythrocytic vaccine approach may enhance protection compared to CSP-only vaccines. This lays the groundwork for further studies aimed at testing the identified antigen combinations in human vaccination trials that assess efficacy with controlled human malaria infection. The currently approved malaria vaccine targets a single parasite protein (CSP) and results in only partial protection. We tested several additional vaccine targets in combination with CSP to identify those that could enhance protection from infection upon challenge in the mouse malaria model. In identifying several such enhancing vaccine targets, our work indicates that a multiprotein immunization approach may be a promising avenue to achieving higher levels of protection from infection. Our work identified several candidate leads for follow-up in the models relevant for human malaria and provides an experimental framework for efficiently carrying out such screens for other combinations of vaccine targets.

摘要

引起疟疾的寄生虫具有复杂的生命周期,并呈现出众多可能有助于产生保护性免疫反应的抗原靶点。目前推荐的疫苗RTS,S通过靶向恶性疟原虫环子孢子蛋白(CSP)发挥作用,CSP是子孢子形式中最丰富的表面蛋白,负责启动对人类宿主的感染。尽管RTS,S仅显示出中等效力,但它为下一代亚单位疫苗的开发奠定了坚实基础。我们之前对疟原虫子孢子表面蛋白质组的研究确定了其他非CSP抗原,这些抗原单独或与CSP联合使用时可能用作免疫原。在本研究中,我们以啮齿动物疟原虫约氏疟原虫为模型系统,检测了八种此类抗原。我们证明,尽管这些抗原单独提供的保护较弱,但将其中几种抗原与CSP共同免疫可显著增强单独CSP免疫所实现的无菌保护。因此,我们的工作提供了令人信服的证据,表明与仅使用CSP的疫苗相比,多抗原前体红细胞疫苗方法可能增强保护作用。这为进一步研究奠定了基础,这些研究旨在在评估可控人类疟疾感染疗效的人类疫苗试验中测试所确定的抗原组合。目前批准的疟疾疫苗靶向单一寄生虫蛋白(CSP),仅提供部分保护。我们将几种其他疫苗靶点与CSP联合测试,以确定那些在小鼠疟疾模型中受到攻击时可增强抗感染保护的靶点。在确定了几种此类增强疫苗靶点后,我们的工作表明多蛋白免疫方法可能是实现更高水平抗感染保护的一条有前景的途径。我们的工作确定了几个在与人类疟疾相关的模型中进行后续研究的候选先导物,并提供了一个实验框架,用于高效地对其他疫苗靶点组合进行此类筛选。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b475/10100930/06e2ff70f8d5/spectrum.03791-22-f001.jpg

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