National Clinical Research Center for Geriatrics and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Department of Arboviral Vaccine, National Institutes for Food and Drug Control, Beijing, China.
J Med Virol. 2024 Mar;96(3):e29454. doi: 10.1002/jmv.29454.
Various vaccines have been challenged by SARS-CoV-2 variants. Here, we reported a yeast-derived recombinant bivalent vaccine (Bivalent wild-type [Wt]+De) based on the wt and Delta receptor-binding domain (RBD). Yeast derived RBD proteins based on the wt and Delta mutant were used as the prime vaccine. It was found that, in the presence of aluminium hydroxide (Alum) and unmethylated CpG-oligodeoxynucleotides (CpG) adjuvants, more cross-protective immunity against SARS-CoV-2 prototype and variants were elicited by bivalent vaccine than monovalent wtRBD or Delta RBD. Furthermore, a heterologous boosting strategy consisting of two doses of bivalent vaccines followed by one dose adenovirus vectored vaccine exhibited cross-neutralization capacity and specific T cell responses against Delta and Omicron (BA.1 and BA.4/5) variants in mice, superior to a homologous vaccination strategy. This study suggested that heterologous prime-boost vaccination with yeast-derived bivalent protein vaccine could be a potential approach to address the challenge of emerging variants.
多种疫苗都受到了 SARS-CoV-2 变体的挑战。在这里，我们报告了一种基于野生型（wt）和 Delta 受体结合域（RBD）的酵母衍生重组二价疫苗（Bivalent wild-type [Wt]+De）。使用基于 wt 和 Delta 突变体的酵母衍生 RBD 蛋白作为基础疫苗。结果发现，在铝佐剂（Alum）和未甲基化 CpG 寡脱氧核苷酸（CpG）佐剂存在的情况下，二价疫苗比单价 wtRBD 或 Delta RBD 更能引发针对 SARS-CoV-2 原型和变体的交叉保护免疫。此外，由两剂二价疫苗和一剂腺病毒载体疫苗组成的异源加强策略在小鼠中表现出针对 Delta 和奥密克戎（BA.1 和 BA.4/5）变体的交叉中和能力和特异性 T 细胞反应，优于同源疫苗接种策略。这项研究表明，使用酵母衍生的二价蛋白疫苗进行异源初免-加强接种可能是应对新出现变体挑战的一种潜在方法。
