CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China.
Stemirna Therapeutics, Shanghai, China.
PLoS Pathog. 2024 Apr 1;20(4):e1012116. doi: 10.1371/journal.ppat.1012116. eCollection 2024 Apr.
Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, continues to mutate and generates new variants with increasingly severe immune escape, urging the upgrade of COVID-19 vaccines. Here, based on a similar dimeric RBD design as our previous ZF2001 vaccine, we developed a novel broad-spectrum COVID-19 mRNA vaccine, SWIM516, with chimeric Delta-BA.2 RBD dimer delivered by lipopolyplex (LPP). Unlike the popular lipid nanoparticle (LNP), this LPP-delivered mRNA expresses only in the injection site, which avoids potential toxicity to the liver. We demonstrated the broad-spectrum humoral and cellular immunogenicity of this vaccine to Delta and Omicron sub-variants in naïve mice and as booster shots. When challenged with Delta or Omicron live virus, vaccinated human angiotensin-converting enzyme (hACE2) transgenic mice and rhesus macaques were both protected, displaying significantly reduced viral loads and markedly relieved pathological damages. We believe the SWIM516 vaccine qualifies as a candidate for the next-generation broad-spectrum COVID-19 vaccine.
自 2019 年冠状病毒病（COVID-19）大流行开始以来，COVID-19 的病原体严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）不断发生突变，并产生具有越来越严重免疫逃逸能力的新变体，促使 COVID-19 疫苗不断升级。在这里，基于我们之前 ZF2001 疫苗的类似二聚体 RBD 设计，我们开发了一种新型广谱 COVID-19 mRNA 疫苗 SWIM516，其使用脂多聚复合物（LPP）递送嵌合 Delta-BA.2 RBD 二聚体。与流行的脂质纳米颗粒（LNP）不同，这种 LPP 递送的 mRNA 仅在注射部位表达，从而避免了对肝脏的潜在毒性。我们在未经免疫的小鼠中证明了这种疫苗对 Delta 和 Omicron 亚变体的广谱体液和细胞免疫原性，并且作为加强针也具有这种效果。当用 Delta 或 Omicron 活病毒进行攻毒时，接种疫苗的人类血管紧张素转换酶（hACE2）转基因小鼠和恒河猴均受到保护，病毒载量显著降低，病理损伤明显缓解。我们相信 SWIM516 疫苗有资格成为下一代广谱 COVID-19 疫苗的候选者。
