PDF(Pubmed)
Abstract：
Urgent research into innovative severe acute respiratory coronavirus-2 (SARS-CoV-2) vaccines that may successfully prevent various emerging emerged variants, particularly the Omicron variant and its subvariants, is necessary. Here, we designed a chimeric adenovirus-vectored vaccine named Ad5-Beta/Delta. This vaccine was created by incorporating the receptor-binding domain from the Delta variant, which has the L452R and T478K mutations, into the complete spike protein of the Beta variant. Both intramuscular (IM) and intranasal (IN) vaccination with Ad5-Beta/Deta vaccine induced robust broad-spectrum neutralization against Omicron BA.5-included variants. IN immunization with Ad5-Beta/Delta vaccine exhibited superior mucosal immunity, manifested by higher secretory IgA antibodies and more tissue-resident memory T cells (TRM) in respiratory tract. The combination of IM and IN delivery of the Ad5-Beta/Delta vaccine was capable of synergically eliciting stronger systemic and mucosal immune responses. Furthermore, the Ad5-Beta/Delta vaccination demonstrated more effective boosting implications after two dosages of mRNA or subunit recombinant protein vaccine, indicating its capacity for utilization as a booster shot in the heterologous vaccination. These outcomes quantified Ad5-Beta/Delta vaccine as a favorable vaccine can provide protective immunity versus SARS-CoV-2 pre-Omicron variants of concern and BA.5-included Omicron subvariants.
摘要：
紧急研究创新的严重急性呼吸道冠状病毒-2（SARS-CoV-2）疫苗，可以成功地防止各种新出现的变种，特别是Omicron变体及其亚变体，是必要的。这里,我们设计了一种嵌合腺病毒载体疫苗,命名为Ad5-Beta/Delta.这种疫苗是通过整合来自Delta变体的受体结合结构域而产生的，有L452R和T478K突变,变成β变体的完整刺突蛋白。用Ad5-β/Deta疫苗进行的肌内（IM）和鼻内（IN）疫苗接种均诱导了针对包含OmicronBA.5的变体的强大的广谱中和。用Ad5-Beta/Delta疫苗进行的IN免疫表现出优异的粘膜免疫，表现为较高的分泌性IgA抗体和呼吸道中更多的组织驻留记忆T细胞（TRM）。Ad5-β/δ疫苗的IM和IN递送的组合能够协同地引发更强的全身和粘膜免疫应答。此外，在两个剂量的mRNA或亚单位重组蛋白疫苗后，Ad5-Beta/Delta疫苗接种显示出更有效的增强作用，表明其在异源疫苗接种中作为加强剂的利用能力。这些结果定量的Ad5-β/Delta疫苗作为有利的疫苗可以提供相对于关注的SARS-CoV-2pre-Omicron变体和包含BA.5的Omicron亚变体的保护性免疫。
