The SARS-CoV-2 Omicron subvariant BA.5 rapidly spread worldwide and replaced BA.1/BA.2 in many countries, becoming globally dominant. BA.5 has unique amino acid substitutions in the spike protein that both mediate immune escape from neutralizing antibodies produced by immunizations and increase ACE2 receptor binding affinity. In a comprehensive, long-term (up to 9 months post primary vaccination), experimental vaccination study using male Syrian hamsters, we evaluate neutralizing antibody responses and efficacy against BA.5 challenge after primary vaccination with Ad26.COV2.S (Janssen) or BNT162b2 (Pfizer/BioNTech) followed by a homologous or heterologous booster with mRNA-1273 (Moderna) or NVX-CoV2373 (Novavax). Notably, one high or low dose of Ad26.COV2.S provides more durable immunity than two primary doses of BNT162b2, and the NVX-CoV2373 booster provides the strongest augmentation of immunity, reduction in BA.5 viral replication, and disease. Our data demonstrate the immunogenicity and efficacy of different prime/boost vaccine regimens against BA.5 infection in an immune-competent model and provide new insights regarding COVID-19 vaccine strategies.

SARS-CoV-2 Omicron 亚变体 BA.5 在全球范围内迅速传播，并在许多国家取代了 BA.1/BA.2，成为全球主导。BA.5 在刺突蛋白中具有独特的氨基酸取代，既能介导免疫逃避免疫产生的中和抗体，又能增加 ACE2 受体结合亲和力。在一项使用雄性叙利亚仓鼠的全面、长期（初次接种后最多 9 个月）的实验性疫苗接种研究中，我们评估了初次接种 Ad26.COV2.S (Janssen) 或 Ad26.COV2.S (Janssen) 后针对 BA.5 攻击的中和抗体反应和功效。 BNT162b2 (Pfizer/BioNTech)，然后是含有 mRNA-1273 (Moderna) 或 NVX-CoV2373 (Novavax) 的同源或异源加强剂。值得注意的是，一剂高剂量或低剂量的 Ad26.COV2.S 比两剂初级剂量的 BNT162b2 提供更持久的免疫力，而 NVX-CoV2373 加强剂可提供最强的免疫力增强作用，减少 BA.5 病毒复制和疾病。我们的数据证明了在免疫活性模型中针对 BA.5 感染的不同初免/加强疫苗方案的免疫原性和功效，并提供了有关 COVID-19 疫苗策略的新见解。