Immunization with attenuated Plasmodium falciparum sporozoites (PfSPZs) has been shown to be protective against malaria, but the features of the antibody response induced by this treatment remain unclear. To investigate this response in detail, we isolated IgM and IgG monoclonal antibodies from Tanzanian volunteers who were immunized with repeated injection of Sanaria PfSPZ Vaccine and who were found to be protected from controlled human malaria infection with infectious homologous PfSPZs. All isolated IgG monoclonal antibodies bound to P. falciparum circumsporozoite protein (PfCSP) and recognized distinct epitopes in its N terminus, NANP-repeat region, and C terminus. Strikingly, the most effective antibodies, as determined in a humanized mouse model, bound not only to the repeat region, but also to a minimal peptide at the PfCSP N-terminal junction that is not in the RTS,S vaccine. These dual-specific antibodies were isolated from different donors and were encoded by VH3-30 or VH3-33 alleles that encode tryptophan or arginine at position 52. Using structural and mutational data, we describe the elements required for germline recognition and affinity maturation. Our study provides potent neutralizing antibodies and relevant information for lineage-targeted vaccine design and immunization strategies.

中文翻译：

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通过与环子孢子蛋白的双重结合有效抑制疟疾感染的公共抗体谱系。

减毒恶性疟原虫子孢子（PfSPZs）的免疫接种已显示出对疟疾的保护作用，但这种治疗诱导的抗体应答特征尚不清楚。为了详细研究这种反应，我们从坦桑尼亚志愿者中分离出了IgM和IgG单克隆抗体，这些志愿者通过反复注射Sanaria PfSPZ疫苗进行了免疫，并被发现可以预防感染性同源PfSPZ的受控人类疟疾感染。所有分离的IgG单克隆抗体均与恶性疟原虫环子孢子蛋白（PfCSP）结合，并在其N末端，NANP重复区域和C末端识别出不同的表位。令人惊讶的是，在人源化小鼠模型中确定的最有效的抗体不仅与重复区域结合，还要在Rfs，S疫苗中没有的PfCSP N末端连接处形成最小的肽段。这些双特异性抗体是从不同的供体中分离出来的，由在位置52上编码色氨酸或精氨酸的VH3-30或VH3-33等位基因编码。使用结构和突变数据，我们描述了种系识别和亲和力成熟所需的元素。我们的研究为针对谱系的疫苗设计和免疫策略提供了有效的中和抗体和相关信息。