Gontu Abhinay, Misra Sougat, Chothe Shubhada K, Ramasamy Santhamani, Jakka Padmaja, Byukusenge Maurice, LaBella Lindsey C, Nair Meera Surendran, Jayarao Bhushan M, Archetti Marco, Nissly Ruth H, Kuchipudi Suresh V
Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA, USA.
Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, PA, USA.
NPJ Vaccines. 2025 Jun 3;10(1):110. doi: 10.1038/s41541-025-01166-1.
SARS-CoV-2 continues to evolve and evade vaccine immunity necessitating vaccines that offer broad protection across variants. Conventional mRNA vaccines face cost and scalability challenges, prompting the exploration of alternative platforms like trans-amplifying (TA) mRNA that offer advantages in safety, manufacturability, and antigen dose optimization. Using consensus sequence of immunodominant antigens is a promising antigen design strategy for board cross-protection. Combining these two features, we designed and evaluated a TA mRNA vaccine encoding a consensus spike protein from SARS-CoV-2. Mice receiving the TA mRNA vaccine produced neutralizing antibody levels comparable to a conventional mRNA vaccine using 40 times less antigen mRNA. In hACE2 transgenic mice challenged with the Omicron BA.1 variant, the TA mRNA vaccine reduced lung viral titers by over 10-fold and induced broadly cross-neutralizing antibodies against multiple variants. These findings highlight the potential of TA mRNA vaccines with consensus antigen design, to improve efficacy and adaptability against SARS-CoV-2 variants.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）不断进化并逃避疫苗免疫，因此需要能对多种变体提供广泛保护的疫苗。传统的信使核糖核酸（mRNA）疫苗面临成本和可扩展性挑战，这促使人们探索如转扩增（TA）mRNA等替代平台，这些平台在安全性、可制造性和抗原剂量优化方面具有优势。使用免疫显性抗原的共有序列是一种有前景的抗原设计策略，可实现广泛的交叉保护。结合这两个特点，我们设计并评估了一种编码SARS-CoV-2共有刺突蛋白的TA mRNA疫苗。接种该TA mRNA疫苗的小鼠产生的中和抗体水平与使用抗原mRNA量少40倍的传统mRNA疫苗相当。在用奥密克戎BA.1变体攻击的人血管紧张素转换酶2（hACE2）转基因小鼠中，TA mRNA疫苗使肺部病毒滴度降低了10倍以上，并诱导产生了针对多种变体的广泛交叉中和抗体。这些发现凸显了具有共有抗原设计的TA mRNA疫苗在提高针对SARS-CoV-2变体的效力和适应性方面的潜力。
