Sanders John W, Ewing Daniel, Sundaram Appavu K, Gamble Christopher Scott, Blevins Maria, Liang Zhaodong, Sanders Leigh Ann, Ornelles David A, Sun Peifang, Lenart Klara, Feuerstein Hendrik, Loré Karin, Petrovsky Nikolai, Williams Maya, Porter Kevin R
Section on Infectious Diseases, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Agile Vaccines and Therapeutics Department, Naval Medical Research Command, Silver Spring, MD 20910, USA.
Vaccines (Basel). 2024 Apr 24;12(5):451. doi: 10.3390/vaccines12050451.
COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has significantly impacted public health and the economy worldwide. Most of the currently licensed COVID-19 vaccines act by inhibiting the receptor-binding function of the SARS-CoV-2 spike protein. The constant emergence of SARS-CoV-2 variants resulting from mutations in the receptor-binding domain (RBD) leads to vaccine immune evasion and underscores the importance of broadly acting COVID-19 vaccines. Inactivated whole virus vaccines can elicit broader immune responses to multiple epitopes of several antigens and help overcome such immune evasions. We prepared a psoralen-inactivated SARS-CoV-2 vaccine (SARS-CoV-2 PsIV) and evaluated its immunogenicity and efficacy in nonhuman primates (NHPs) when administered with the Advax-CpG adjuvant. We also evaluated the SARS-CoV-2 PsIV as a booster shot in animals vaccinated with a DNA vaccine that can express the full-length spike protein. The Advax-CpG-adjuvanted SARS-CoV-2 PsIV elicited a dose-dependent neutralizing antibody response in the NHPs, as measured using a serum microneutralization assay against the SARS-CoV-2 Washington strain and the Delta variant. The animals vaccinated with the DNA vaccine followed by a boosting dose of the SARS-CoV-2 PsIV exhibited the highest neutralizing antibody responses and were able to quickly clear infection after an intranasal challenge with the SARS-CoV-2 Delta variant. Overall, the data show that the Advax-CpG-adjuvanted SARS-CoV-2 PsIV, either by itself or as a booster shot following nucleic acid (NA) vaccines, has the potential to protect against emerging variants.
由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起的2019冠状病毒病（COVID-19）对全球公共卫生和经济产生了重大影响。目前大多数已获许可的COVID-19疫苗通过抑制SARS-CoV-2刺突蛋白的受体结合功能发挥作用。受体结合域（RBD）突变导致的SARS-CoV-2变体不断出现，导致疫苗免疫逃逸，凸显了作用广泛的COVID-19疫苗的重要性。灭活全病毒疫苗可引发对多种抗原多个表位的更广泛免疫反应，并有助于克服此类免疫逃逸。我们制备了一种补骨脂素灭活的SARS-CoV-2疫苗（SARS-CoV-2 PsIV），并评估了其与Advax-CpG佐剂联合使用时在非人类灵长类动物（NHP）中的免疫原性和效力。我们还评估了SARS-CoV-2 PsIV作为接种可表达全长刺突蛋白的DNA疫苗的动物的加强针的效果。使用针对SARS-CoV-2华盛顿毒株和Delta变体的血清微量中和试验测量，Advax-CpG佐剂的SARS-CoV-2 PsIV在NHP中引发了剂量依赖性中和抗体反应。接种DNA疫苗后再接种一剂SARS-CoV-2 PsIV加强针的动物表现出最高的中和抗体反应，并且在用SARS-CoV-2 Delta变体进行鼻内攻击后能够迅速清除感染。总体而言，数据表明，Advax-CpG佐剂的SARS-CoV-2 PsIV本身或作为核酸（NA）疫苗后的加强针，都有可能预防新出现的变体。
