Awakoaiye Bakare, Li Shiyi, Sanchez Sarah, Dangi Tanushree, Irani Nahid, Arroyo Laura, Arellano Gabriel, Mohammadabadi Shadi, Aid Malika, Penaloza-MacMaster Pablo
Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
bioRxiv. 2025 Jul 17:2025.07.16.665159. doi: 10.1101/2025.07.16.665159.
Despite the widespread use of adenovirus, mRNA, and protein-based vaccines during the COVID-19 pandemic, their relative immunological profiles and protective efficacies remain incompletely defined. Here, we compared antigen kinetics, innate and adaptive immune responses, and protective efficacy following Ad5, mRNA, and protein vaccination in mice. Ad5 induced the most sustained antigen expression, but mRNA induced the most potent interferon responses, associated with robust antigen presentation and costimulation. Unlike Ad5 vaccines, which were hindered by pre-existing vector immunity, mRNA vaccines retained efficacy after repeated use. As a single-dose regimen, Ad5 vaccines elicited superior immune responses. However, as a prime-boost regimen, and particularly in Ad5 seropositive mice, mRNA vaccines outperformed the other vaccine platforms. These findings highlight strengths of each vaccine platform and underscore the importance of host serostatus in determining optimal vaccine performance.
尽管在新冠疫情期间腺病毒疫苗、mRNA疫苗和蛋白质疫苗得到广泛使用，但其相对的免疫特征和保护效力仍未完全明确。在此，我们比较了小鼠接种Ad5疫苗、mRNA疫苗和蛋白质疫苗后的抗原动力学、先天性和适应性免疫反应以及保护效力。Ad5疫苗诱导的抗原表达持续时间最长，但mRNA疫苗诱导的干扰素反应最强，且与强大的抗原呈递和共刺激相关。与受预先存在的载体免疫阻碍的Ad5疫苗不同，mRNA疫苗在重复使用后仍保持效力。作为单剂量方案，Ad5疫苗引发的免疫反应更优。然而，作为初免-加强方案，尤其是在Ad5血清阳性小鼠中，mRNA疫苗的表现优于其他疫苗平台。这些发现突出了每种疫苗平台的优势，并强调了宿主血清状态在确定最佳疫苗性能方面的重要性。
