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佐剂增强 SARS-CoV-2 RBD 的免疫原性,并支持抗体在小鼠中的母胎转移。

Adjuvants to increase immunogenicity of SARS-CoV-2 RBD and support maternal-fetal transference of antibodies in mice.

机构信息

Immunology Center, Adolfo Lutz Institute, 11th floor, room 1116, Av Dr Arnaldo, 355, Pacaembu, 01246-902 São Paulo, SP, Brazil.

Graduate Program Interunits in Biotechnology, University of São Paulo, Av Prof Lineu Prestes, 2415, ICB Hall III, Cidade Universitária, 05508-900, São Paulo, SP, Brazil.

出版信息

Pathog Dis. 2022 Oct 19;80(1). doi: 10.1093/femspd/ftac038.

Abstract

Adjuvants are important components of vaccines, increasing immunogenicity and modulating the immune response. SARS-CoV-2 vaccines are still being developed in order to improve worldwide access to immunization. Specific populations should be addressed in these investigations, such as pregnant women-to protect both mothers and neonates. In this study, female adult mice were immunized with Receptor-binding domain (RBD) from SARS-CoV-2 adjuvanted by a mixture of DDA and Saponin and put to mating to verify the maternal transference of IgG. For comparison, other group received RBD adjuvanted by OMVs from Neisseria meningitidis and Alum. The adjuvants enhanced IgG production and neutralization. DDA/Sap contributed to increase IgG1, IgG2a, IgG2b, and IgG3 isotypes. Total IgG avidity was considered high, as well as IgG1, IgG2a, and IgG2b avidity. IgG antibodies were effectively transferred to the offspring, predominantly IgG2a, IgG2b, and IgG3. The passive transferred immunoglobulin maintained the neutralizing ability, although it lost avidity. ELISA data was confirmed in Dot-ELISA and immunoblotting assays. DDA and Saponin seem a promising adjuvant mixture to enhance the humoral response of SARS-CoV-2 antigens. Further studies considering the effects of maternal immunization in the protection of offspring are needed, regardless the platform used in COVID-19 vaccines.

摘要

佐剂是疫苗的重要组成部分,可提高免疫原性并调节免疫反应。为了改善全球范围内的免疫接种机会,仍在开发针对 SARS-CoV-2 的疫苗。在这些研究中,应针对特定人群,例如孕妇,以保护母亲和新生儿。在这项研究中,成年雌性小鼠用 SARS-CoV-2 的受体结合域(RBD)免疫,佐剂为 DDA 和皂苷的混合物,并进行交配以验证 IgG 的母体转移。为了进行比较,另一组接受了脑膜炎奈瑟菌 OMV 佐剂和 Alum 佐剂的 RBD。佐剂增强了 IgG 的产生和中和作用。DDA/Sap 有助于增加 IgG1、IgG2a、IgG2b 和 IgG3 同种型。总 IgG 亲和力被认为很高,如 IgG1、IgG2a 和 IgG2b 亲和力。IgG 抗体有效地转移到后代,主要是 IgG2a、IgG2b 和 IgG3。被动转移的免疫球蛋白保持了中和能力,尽管它失去了亲和力。ELISA 数据在 Dot-ELISA 和免疫印迹分析中得到了证实。DDA 和皂苷似乎是一种很有前途的佐剂混合物,可以增强 SARS-CoV-2 抗原的体液反应。无论 COVID-19 疫苗使用哪种平台,都需要进一步研究母体免疫对保护后代的影响。

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