Omicron SARS-CoV-2 variants escape vaccine-induced neutralizing antibodies and cause nearly all current COVID-19 cases. Here, we compared the efficacy of three booster vaccines against Omicron BA.5 challenge in rhesus macaques: mRNA-1273, the Novavax ancestral spike protein vaccine (NVX-CoV2373), or Omicron BA.1 spike protein version (NVX-CoV2515). All three booster vaccines induced a strong BA.1 cross-reactive binding antibody and changed immunoglobulin G dominance from IgG1 to IgG4 in the serum. All three booster vaccines also induced strong and comparable neutralizing antibody responses against multiple variants of concern, including BA.5 and BQ.1.1, along with long-lived plasma cells in the bone marrow. The ratio of BA.1 to WA-1 spike-specific antibody-secreting cells in the blood was higher in NVX-CoV2515 animals compared to NVX-CoV2373 animals, suggesting a better recall of BA.1 specific memory B cells by the BA.1 spike-specific vaccine compared to the ancestral spike-specific vaccine. Further, all three booster vaccines induced low levels of spike-specific CD4 but not CD8 T cell responses in the blood. Following challenge with SARS-CoV-2 BA.5 variant, all three vaccines showed strong protection in the lungs and controlled virus replication in the nasopharynx. In addition, both Novavax vaccines blunted viral replication in nasopharynx at day 2. The protection against SARS-CoV-2 BA.5 infection in the upper respiratory airways correlated with binding, neutralizing, and ADNP activities of the serum antibody. These data have important implications for COVID-19 vaccine development, as vaccines that lower nasopharyngeal virus may help to reduce transmission.

中文翻译：

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mRNA-1273 和 Novavax 祖先或 BA.1 刺突加强疫苗对非人类灵长类动物中 SARS-CoV-2 BA.5 感染的功效

Omicron SARS-CoV-2 变体逃避了疫苗诱导的中和抗体，并导致了几乎所有当前的 COVID-19 病例。在这里，我们比较了三种加强疫苗针对恒河猴 Omicron BA.5 攻击的功效：mRNA-1273、Novavax 祖先刺突蛋白疫苗 (NVX-CoV2373) 或 Omicron BA.1 刺突蛋白版本 (NVX-CoV2515)。所有三种加强疫苗均诱导产生强 BA.1 交叉反应结合抗体，并将血清中免疫球蛋白 G 的优势从 IgG1 改变为 IgG4。所有三种加强疫苗还针对多种关注的变体（包括 BA.5 和 BQ.1.1）以及骨髓中的长寿命浆细胞诱导了强烈且相当的中和抗体反应。与 NVX-CoV2373 动物相比，NVX-CoV2515 动物血液中 BA.1 与 WA-1 刺突特异性抗体分泌细胞的比例较高，表明 BA 更好地回忆 BA.1 特异性记忆 B 细胞。 1 与祖先的刺突特异性疫苗相比的刺突特异性疫苗。此外，所有三种加强疫苗均在血液中诱导低水平的刺突特异性 CD4 而非 CD8 T 细胞反应。在接受 SARS-CoV-2 BA.5 变体攻击后，所有三种疫苗都对肺部表现出强大的保护作用，并控制了鼻咽部的病毒复制。此外，两种 Novavax 疫苗均在第 2 天抑制了鼻咽部的病毒复制。上呼吸道对 SARS-CoV-2 BA.5 感染的保护与血清抗体的结合、中和和 ADNP 活性相关。这些数据对 COVID-19 疫苗的开发具有重要意义，因为降低鼻咽病毒的疫苗可能有助于减少传播。