三种通过麻疹和风疹疫苗经鼻腔递送的 SARS-CoV-2 刺突蛋白变体具有广泛的保护作用。

Three SARS-CoV-2 spike protein variants delivered intranasally by measles and mumps vaccines are broadly protective.

机构信息

Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, USA.

Department of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, OH, USA.

出版信息

Nat Commun. 2024 Jul 3;15(1):5589. doi: 10.1038/s41467-024-49443-2.

DOI:10.1038/s41467-024-49443-2

PMID:38961063

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11222507/

Abstract

As the new SARS-CoV-2 Omicron variants and subvariants emerge, there is an urgency to develop intranasal, broadly protective vaccines. Here, we developed highly efficacious, intranasal trivalent SARS-CoV-2 vaccine candidates (TVC) based on three components of the MMR vaccine: measles virus (MeV), mumps virus (MuV) Jeryl Lynn (JL1) strain, and MuV JL2 strain. Specifically, MeV, MuV-JL1, and MuV-JL2 vaccine strains, each expressing prefusion spike (preS-6P) from a different variant of concern (VoC), were combined to generate TVCs. Intranasal immunization of IFNAR1 mice and female hamsters with TVCs generated high levels of S-specific serum IgG antibodies, broad neutralizing antibodies, and mucosal IgA antibodies as well as tissue-resident memory T cells in the lungs. The immunized female hamsters were protected from challenge with SARS-CoV-2 original WA1, B.1.617.2, and B.1.1.529 strains. The preexisting MeV and MuV immunity does not significantly interfere with the efficacy of TVC. Thus, the trivalent platform is a promising next-generation SARS-CoV-2 vaccine candidate.

摘要

随着新型 SARS-CoV-2 奥密克戎变体和亚变体的出现，开发鼻内、广泛保护的疫苗迫在眉睫。在这里，我们基于麻疹病毒（MeV）、腮腺炎病毒（MuV）Jeryl Lynn（JL1）株和 MuV JL2 株这三种成分开发了高效的鼻内三价 SARS-CoV-2 疫苗候选物（TVC）。具体来说，将表达不同关注变体（VoC）的前融合刺突（preS-6P）的 MeV、MuV-JL1 和 MuV-JL2 疫苗株组合在一起生成 TVC。用 TVC 对 IFNAR1 小鼠和雌性仓鼠进行鼻内免疫，可在肺部产生高水平的 S 特异性血清 IgG 抗体、广谱中和抗体和黏膜 IgA 抗体以及组织驻留记忆 T 细胞。免疫雌性仓鼠可免受 SARS-CoV-2 原始 WA1、B.1.617.2 和 B.1.1.529 株的挑战。预先存在的 MeV 和 MuV 免疫不会显著干扰 TVC 的功效。因此，三价平台是一种有前途的下一代 SARS-CoV-2 疫苗候选物。