PDF(Pubmed)
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：
随着新的SARS-CoV-2Omicron变体和亚变体的出现，迫切需要鼻内发育，广泛的保护性疫苗。这里,我们开发了高效的，鼻内三价SARS-CoV-2候选疫苗（TVC）基于MMR疫苗的三个组成部分：麻疹病毒（MeV），腮腺炎病毒（MuV）JerylLynn（JL1）株，和MuVJL2菌株。具体来说,MeV,MuV-JL1和MuV-JL2疫苗株，每个表达来自不同关注变体（VoC）的融合前尖峰（preS-6P），组合产生TVC。用TVC鼻内免疫IFNAR1-/-小鼠和雌性仓鼠产生高水平的S特异性血清IgG抗体，广泛的中和抗体，和粘膜IgA抗体以及肺中的组织驻留记忆T细胞。免疫的雌性仓鼠免受SARS-CoV-2原始WA1，B.1.617.2和B.1.1.29菌株的攻击。先前存在的MeV和MuV免疫不会显著干扰TVC的功效。因此，三价平台是有希望的下一代SARS-CoV-2疫苗候选物。
