Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, International Joint Research Center for Intelligent Biosensing Technology and Health, Hubei International Scientific and Technological Cooperation Base of Pesticide and Green Synthesis, College of Chemistry, Central China Normal University, Wuhan, 430079, China.
CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China.
Chem Commun (Camb). 2022 Feb 10;58(13):2120-2123. doi: 10.1039/d1cc06520c.
The coronavirus 2019 (COVID-19) pandemic is causing serious impacts in the world, and safe and effective vaccines and medicines are the best methods to combat the disease. The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein plays a key role in interacting with the angiotensin-converting enzyme 2 (ACE2) receptor, and is regarded as an important target of vaccines. Herein, we constructed the adjuvant-protein conjugate PamCSK-RBD as a vaccine candidate, in which the -terminal of the RBD was site-selectively oxidized by transamination and conjugated with the TLR1/2 agonist PamCSK. This demonstrated that the conjugation of PamCSK significantly enhanced the anti-RBD antibody response and cellular response. In addition, sera from the PamCSK-RBD immunized group efficiently inhibited the binding of the RBD to ACE2 and protected cells from SARS-CoV-2 and four variants of concern (alpha, beta, gamma and delta), indicating that this adjuvant strategy could be one of the effective means for protein vaccine development.
新型冠状病毒（COVID-19）大流行正在全球造成严重影响，安全有效的疫苗和药物是抗击该疾病的最佳方法。SARS-CoV-2 刺突蛋白的受体结合域（RBD）在与血管紧张素转换酶 2（ACE2）受体相互作用中起着关键作用，被认为是疫苗的重要靶点。在此，我们构建了佐剂-蛋白缀合物 PamCSK-RBD 作为候选疫苗，其中 RBD 的 -端通过转氨基作用被选择性氧化，并与 TLR1/2 激动剂 PamCSK 缀合。这表明 PamCSK 的缀合显著增强了抗 RBD 抗体反应和细胞反应。此外，来自 PamCSK-RBD 免疫组的血清有效地抑制了 RBD 与 ACE2 的结合，并保护细胞免受 SARS-CoV-2 和四个关注变体（alpha、beta、gamma 和 delta）的侵害，表明这种佐剂策略可能是蛋白疫苗开发的有效手段之一。
