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首页> 外文期刊>Infection and immunity >Efficacy of Opsonic and Nonopsonic Serotype 3 Pneumococcal Capsular Polysaccharide-Specific Monoclonal Antibodies against Intranasal Challenge with Streptococcus pneumoniae in Mice
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Efficacy of Opsonic and Nonopsonic Serotype 3 Pneumococcal Capsular Polysaccharide-Specific Monoclonal Antibodies against Intranasal Challenge with Streptococcus pneumoniae in Mice

机译：调理和非调理血清型3肺炎球菌荚膜多糖特异性单克隆抗体抗小鼠肺炎链球菌鼻内攻击的功效。

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Serotype-specific antibodies to pneumococcal capsular polysaccharide (PPS) are a critical component of vaccine-mediated immunity to Streptococcus pneumoniae. In this study, we investigated the in vitro opsonophagocytic activities of three PPS-specific mouse immunoglobulin G1 monoclonal antibodies (MAbs), 1E2, 5F6, and 7A9, and determined their in vivo efficacies against intranasal challenge with WU2, a serotype 3 pneumococcal strain, in normal and immunodeficient mice. The MAbs had different in vitro activities in a pneumococcal killing assay: 7A9 enhanced killing by mouse neutrophils and J774 cells in the presence of a complement source, whereas 5F6 promoted killing in the absence, but not the presence, of complement, and 1E2 did not promote killing under any conditions. Nonetheless, all three MAbs protected normal and complement component 3-deficient mice from a lethal intranasal challenge with WU2 in passive-immunization experiments in which 10 μg of the MAbs were administered intraperitoneally before intranasal challenge. In contrast, only 1E2 protected Fcγ receptor IIB knockout (FcγRIIB KO) mice and mice that were depleted of neutrophils with the MAb RB6, whereas 7A9 and 5F6 required neutrophils and FcγRIIB to mediate protection. Conversely, 7A9 and 5F6 protected FcγR KO mice, but 1E2 did not. Hence, the efficacy of 1E2 required an activating FcγR(s), whereas 5F6 and 7A9 required the inhibitory FcγR (FcγRIIB). Taken together, our data demonstrate that both MAbs that do and do not promote pneumococcal killing in vitro can mediate protection in vivo, although their efficacies depend on different host receptors and/or components.
机译：肺炎球菌荚膜多糖（PPS）的血清型特异性抗体是疫苗介导的肺炎链球菌免疫性的关键组成部分。在这项研究中，我们研究了3种PPS特异性小鼠免疫球蛋白G1单克隆抗体（MAbs）1E2、5F6和7A9的体外调理吞噬活性，并确定了它们对WU2（血清型3肺炎球菌菌株）鼻内攻击的体内疗效，在正常和免疫缺陷小鼠中。在肺炎球菌杀伤试验中，单克隆抗体具有不同的体外活性：在存在补体来源的情况下，7A9增强了小鼠嗜中性粒细胞和J774细胞的杀伤力，而在没有补体（但不存在）的情况下，5F6促进了杀伤力，而1E2没有在任何情况下都促进杀戮。尽管如此，在被动免疫实验中，所有三种MAb均通过WU2保护正常和补体成分3缺陷的小鼠免于致命的鼻内攻击，其中在鼻内攻击前腹膜内施用10μgMAb。相反，只有1E2保护了Fcγ受体IIB敲除（FcγRIIBKO）小鼠和用MAb RB6耗尽了中性粒细胞的小鼠，而7A9和5F6需要中性粒细胞和FcγRIIB来介导保护。相反，7A9和5F6保护FcγRKO小鼠，而1E2没有。因此，1E2的功效需要激活的FcγR，而5F6和7A9则需要抑制性的FcγR（FcγRIIB）。两者合计，我们的数据表明，虽然体外和非体外都促进肺炎球菌的杀伤，但两种MAb均可介导体内保护作用，尽管它们的功效取决于不同的宿主受体和/或组分。

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