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Vaccine. 2022 Feb 23;40(9):1289-1298. doi: 10.1016/j.vaccine.2022.01.021. Epub 2022 Jan 31.
The emergence of SARS-CoV-2 variants, especially Beta and Delta, has raised concerns about the reduced protection from previous infection or vaccination based on the original Wuhan-Hu-1 (D614) virus. To identify promising regimens for inducing neutralizing titers towards new variants, we evaluated monovalent and bivalent mRNA vaccines either as primary vaccination or as a booster in nonhuman primates (NHPs). Two mRNA vaccines, D614-based MRT5500 and Beta-based MRT5500β, tested in sequential regimens or as a bivalent combination in naïve NHPs produced modest neutralizing titers to heterologous variants. However, when mRNA vaccines were administered as a booster to pre-immune NHPs, we observed a robust increase in neutralizing titers with expanded breadth towards all tested variants, and notably SARS-CoV-1. The breadth of the neutralizing response was independent of vaccine sequence or modality, as we further showed either MRT5500 or recombinant subunit Spike protein (with adjuvant) can serve as boosters to induce broadly neutralizing antibodies in the NHPs primed with MRT5500. The data support the notion that a third vaccination is key to boosting existing titers and improving the breadth of antibodies to address variants of concern, including those with an E484K mutation in the Receptor Binding Domain (RBD) (Beta, Gamma).
SARS-CoV-2 变体（特别是 Beta 和 Delta 变体）的出现引起了人们对基于原始武汉-Hu-1（D614）病毒的既往感染或疫苗接种保护效力降低的担忧。为了确定针对新变体产生中和抗体滴度的有前途方案，我们在非人类灵长类动物（NHP）中评估了单价和双价 mRNA 疫苗作为初次接种或加强针的效果。在 NHP 中，我们以序贯方案或双价组合形式测试了两种基于 D614 的 MRT5500 和基于 Beta 的 MRT5500β mRNA 疫苗，结果仅产生了针对异源变体的适度中和抗体滴度。然而，当将 mRNA 疫苗作为加强针用于未免疫的 NHP 时，我们观察到中和抗体滴度显著增加，对所有测试的变体（包括 SARS-CoV-1）的广度也有所扩大。中和反应的广度与疫苗序列或类型无关，因为我们进一步表明，MRT5500 或重组亚单位 Spike 蛋白（佐剂）均可作为加强针，在 MRT5500 免疫的 NHP 中诱导广泛中和抗体。这些数据支持了这样一种观点，即第三次接种是提高现有抗体滴度和提高针对关切变体（包括受体结合域（RBD）中具有 E484K 突变的 Beta、Gamma 变体）的抗体广度的关键。
