The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in over 100 million infections and millions of deaths. Effective vaccines remain the best hope of curtailing SARS-CoV-2 transmission, morbidity, and mortality. The vaccines in current use require cold storage and sophisticated manufacturing capacity, which complicates their distribution, especially in less developed countries. We report the development of a candidate SARS-CoV-2 vaccine that is purely protein based and directly targets antigen-presenting cells. It consists of the SARS-CoV-2 Spike receptor-binding domain (Spike_RBD) fused to an alpaca-derived nanobody that recognizes class II major histocompatibility complex antigens (VHH_MHCII). This vaccine elicits robust humoral and cellular immunity against SARS-CoV-2 and its variants. Both young and aged mice immunized with two doses of VHH_MHCII-Spike_RBD elicit high-titer binding and neutralizing antibodies. Immunization also induces strong cellular immunity, including a robust CD8 T cell response. VHH_MHCII-Spike_RBD is stable for at least 7 d at room temperature and can be lyophilized without loss of efficacy.

由严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 引起的大流行已导致超过 1 亿人感染和数百万人死亡。有效的疫苗仍然是减少 SARS-CoV-2 传播、发病率和死亡率的最大希望。目前使用的疫苗需要冷藏和复杂的制造能力，这使得它们的分配复杂化，尤其是在欠发达国家。我们报告了一种候选 SARS-CoV-2 疫苗的开发，该疫苗完全基于蛋白质并直接针对抗原呈递细胞。它由 SARS-CoV-2 Spike 受体结合域 (Spike _RBD )组成，该结构域与羊驼衍生的纳米抗体融合，该纳米抗体识别 II 类主要组织相容性复合体抗原 (VHH _MHCII）。该疫苗可引发针对 SARS-CoV-2 及其变体的强大体液和细胞免疫。用两剂 VHH _MHCII -Spike _RBD免疫的年轻和年老小鼠均会引发高滴度结合和中和抗体。免疫还诱导强大的细胞免疫，包括强大的 CD8 T 细胞反应。VHH _MHCII -Spike _RBD在室温下至少可稳定保存 7 天，并且可以冻干而不会失去功效。