Society of Fellows, Harvard University, Cambridge, MA 02138;
Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115.
Proc Natl Acad Sci U S A. 2021 Nov 2;118(44). doi: 10.1073/pnas.2116147118.
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) fused to an alpaca-derived nanobody that recognizes class II major histocompatibility complex antigens (VHH). 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-Spike elicit high-titer binding and neutralizing antibodies. Immunization also induces strong cellular immunity, including a robust CD8 T cell response. VHH-Spike is stable for at least 7 d at room temperature and can be lyophilized without loss of efficacy.
由严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 引起的大流行已导致超过 1 亿例感染和数百万人死亡。有效的疫苗仍然是遏制 SARS-CoV-2 传播、发病率和死亡率的最佳希望。目前使用的疫苗需要冷藏和复杂的制造能力，这使得它们的分发变得复杂，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，直接针对抗原呈递细胞。它由 SARS-CoV-2 刺突受体结合域 (Spike) 与识别 II 类主要组织相容性复合物抗原的羊驼衍生纳米抗体 (VHH) 融合而成。该疫苗针对 SARS-CoV-2 及其变体引发强烈的体液和细胞免疫。两剂 VHH-Spike 免疫的年轻和老年小鼠均能诱导高滴度的结合和中和抗体。免疫还诱导强烈的细胞免疫，包括强大的 CD8 T 细胞反应。VHH-Spike 在室温下至少稳定 7 天，并且可以冻干而不会降低功效。
