Alhashimi Marwa, Sayedahmed Ekramy E, Elkashif Ahmed, Chothe Shubhada K, Wang Wen-Chien, Murala Muralimanohara S T, Gairola Vivek, Wakamatsu Nobuko, Gontu Abhinay, Ramasamy Santhamani, LaBella Lindsey, Jakka Padmaja, Nair Meera Surendran, Nissly Ruth H, Kuchipudi Suresh V, Mittal Suresh K
Department of Comparative Pathobiology, and Purdue Institute of Inflammation, Immunology and Infectious Disease, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA.
Department of Infectious Diseases and Microbiology, University of Pittsburgh School of Public Health, Pittsburgh, PA, USA.
NPJ Vaccines. 2025 Jul 19;10(1):159. doi: 10.1038/s41541-025-01198-7.
The emergence of divergent SARS-CoV-2 variants has significantly compromised the effectiveness of first-generation COVID-19 vaccines. We investigated a prime-boost approach using bovine adenoviral (Ad) [BAd] and human Ad (HAd) vectors expressing the spike (S), membrane (M), or nucleocapsid (N) with the autophagy-inducing peptide C5 (AIP-C5) for enhanced antigen-specific immunity. The combinational vaccine formulation expressing three antigens demonstrated markedly elevated antigen-specific cell-mediated immune (CMI) responses compared to groups immunized with vectors expressing individual antigens. Furthermore, vaccinated animals exhibited 100% survival, significant reductions in lung viral titers, and no apparent signs of morbidity following challenges with Delta or Omicron variants in K18-hACE2 transgenic mice. Surprisingly, immunization with vectors expressing M and N resulted in immune suppression. However, including S with M and N overcomes this antagonistic interaction and significantly enhances immune responses and protection efficacy. Using the BAd vaccine platform in a multi-antigen approach complemented with AIP-C5 is a promising strategy for developing next-generation SARS-CoV-2 vaccines.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变异株的出现显著削弱了第一代新冠疫苗的效力。我们研究了一种初免-加强免疫方法，该方法使用表达刺突蛋白（S）、膜蛋白（M）或核衣壳蛋白（N）并带有自噬诱导肽C5（AIP-C5）的牛腺病毒（Ad）[BAd]和人腺病毒（HAd）载体，以增强抗原特异性免疫。与用表达单个抗原的载体免疫的组相比，表达三种抗原的联合疫苗制剂表现出明显升高的抗原特异性细胞介导免疫（CMI）反应。此外，在K18-hACE2转基因小鼠中，接种疫苗的动物在受到德尔塔或奥密克戎变异株攻击后表现出100%的存活率，肺部病毒滴度显著降低，且没有明显的发病迹象。令人惊讶的是，用表达M和N的载体免疫会导致免疫抑制。然而，将S与M和N一起使用可克服这种拮抗相互作用，并显著增强免疫反应和保护效果。在多抗原方法中使用BAd疫苗平台并辅以AIP-C5是开发下一代SARS-CoV-2疫苗的一种有前景的策略。
