Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Department of Immunology, University of Washington, Seattle, WA 98195, USA.
Cell Rep Med. 2022 Oct 18;3(10):100780. doi: 10.1016/j.xcrm.2022.100780. Epub 2022 Sep 26.
Protein nanoparticle scaffolds are increasingly used in next-generation vaccine designs, and several have established records of clinical safety and efficacy. Yet the rules for how immune responses specific to nanoparticle scaffolds affect the immunogenicity of displayed antigens have not been established. Here we define relationships between anti-scaffold and antigen-specific antibody responses elicited by protein nanoparticle immunogens. We report that dampening anti-scaffold responses by physical masking does not enhance antigen-specific antibody responses. In a series of immunogens that all use the same nanoparticle scaffold but display four different antigens, only HIV-1 envelope glycoprotein (Env) is subdominant to the scaffold. However, we also demonstrate that scaffold-specific antibody responses can competitively inhibit antigen-specific responses when the scaffold is provided in excess. Overall, our results suggest that anti-scaffold antibody responses are unlikely to suppress antigen-specific antibody responses for protein nanoparticle immunogens in which the antigen is immunodominant over the scaffold.
蛋白质纳米颗粒支架越来越多地被用于下一代疫苗设计，其中几种已经在临床安全性和疗效方面建立了记录。然而，针对针对纳米颗粒支架的特异性免疫反应如何影响所展示抗原的免疫原性的规则尚未建立。在这里，我们定义了由蛋白质纳米颗粒免疫原引发的针对支架和针对抗原的抗体反应之间的关系。我们报告说，通过物理掩蔽来抑制针对支架的反应并不能增强针对抗原的抗体反应。在一系列均使用相同纳米颗粒支架但显示四种不同抗原的免疫原中，只有 HIV-1 包膜糖蛋白 (Env) 是支架的次要抗原。然而，我们还证明，当提供过量支架时，支架特异性抗体反应可以竞争性抑制针对抗原的反应。总的来说，我们的结果表明，对于抗原在支架上占优势的蛋白质纳米颗粒免疫原，针对支架的抗体反应不太可能抑制针对抗原的抗体反应。
