Increased use of antiviral monoclonal antibodies (mAbs) for treatment and prophylaxis necessitates better understanding of their impact on endogenous immunity to vaccines and viruses. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic presented an opportunity to study immunity in individuals who received antiviral mAbs and were subsequently immunized with vaccines encoding the mAb-targeted viral spike antigen. Here, we describe the impact of administration of an antibody combination, casirivimab plus imdevimab (CAS+IMD), on immune responses to subsequent SARS-CoV-2 vaccination in humans, nonhuman primates, and mice. The presence of CAS+IMD at the time of vaccination led to a specific diminishment of vaccine-elicited pseudovirus neutralizing antibody titers without overall dampening of spike protein–directed immune responses, including antibody, B cell, and T cell responses. The impact on pseudovirus neutralizing titers extended to other therapeutic anti–spike protein antibodies when used as either monotherapy or combination therapy. The specific reduction in pseudovirus neutralizing titers was the result of epitope masking, a phenomenon where specific epitopes are bound by high-affinity antibodies and blocked from B cell recognition. Encouragingly, this reduction in pseudovirus neutralizing titers was reversible with additional booster vaccination. Moreover, by assessing the antiviral immune response in SARS-CoV-2–infected individuals treated therapeutically with CAS+IMD, we demonstrated alteration of antiviral humoral immunity in those who had received mAb therapy, but only in those individuals who had yet to start mounting their natural immune response at the time of mAb treatment. Together, these data demonstrate that antiviral mAbs can alter endogenous humoral immunity during vaccination or infection.

中文翻译：

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针对刺突蛋白的单克隆抗体会改变对 SARS-CoV-2 疫苗接种和感染的内源性体液反应


越来越多地使用抗病毒单克隆抗体 （mAb） 进行治疗和预防，需要更好地了解它们对疫苗和病毒的内源性免疫的影响。严重急性呼吸系统综合症冠状病毒 2 （SARS-CoV-2） 大流行为研究接受抗病毒 mAb 并随后使用编码 mAb 靶向病毒刺突抗原的疫苗进行免疫接种的个体的免疫力提供了机会。在这里，我们描述了抗体组合 casirivimab 加 imdevimab （CAS+IMD） 对人类、非人灵长类动物和小鼠对后续 SARS-CoV-2 疫苗接种的免疫反应的影响。接种疫苗时 CAS+IMD 的存在导致疫苗引发的假病毒中和抗体滴度特异性降低，而不会全面抑制刺突蛋白定向的免疫反应，包括抗体、B 细胞和 T 细胞反应。当用作单一疗法或联合疗法时，对假病毒中和滴度的影响扩展到其他治疗性抗刺突蛋白抗体。假病毒中和滴度的特异性降低是表位掩蔽的结果，表位掩蔽是一种特异性表位被高亲和力抗体结合并被阻断 B 细胞识别的现象。令人鼓舞的是，假病毒中和滴度的这种降低可以通过额外的加强疫苗接种来逆转。此外，通过评估接受 CAS+IMD 治疗治疗的 SARS-CoV-2 感染个体的抗病毒免疫反应，我们证明了接受 mAb 治疗的患者的抗病毒体液免疫发生了改变，但仅限于在 mAb 治疗时尚未开始产生自然免疫反应的个体。 总之，这些数据表明，抗病毒 mAb 可以在疫苗接种或感染期间改变内源性体液免疫。