The Potency of an Anti-MERS Coronavirus Subunit Vaccine Depends on a Unique Combinatorial Adjuvant Formulation
The Potency of an Anti-MERS Coronavirus Subunit Vaccine Depends on a Unique Combinatorial Adjuvant Formulation
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DOI：
10.3390/vaccines8020251
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发表时间：
2020-06-01
期刊：
影响因子：
7.8
通讯作者：
Lustigman, Sara
中科院分区：
文献类型：
--
作者：
George, Parakkal Jovvian;Tai, Wanbo;Lustigman, Sara
疫苗接种是预防人类传染病最成功的策略之一。组合佐剂由于能够刺激多种免疫途径并增强亚单位疫苗的疫苗效力而获得越来越多的关注。利用中东呼吸综合征冠状病毒MERS-CoV受体结合结构域（RBD）疫苗抗原，研究了铝（明矾）与蛋白质佐剂rasp1联合的佐剂性。与RBD +覆盆子-1 +明矾单次接种相比，在两个不同的注射部位分别接种覆盆子-1和铝佐剂RBD疫苗可诱导小鼠产生高度增强的抗mers - cov中和抗体反应。产生的抗体也显著抑制RBD与其细胞相关受体的结合。此外，在不同的部位使用ras -1与铝佐剂RBD疫苗共同免疫，导致引流淋巴结内TfH和GC B细胞的频率增加，这两者都与抗mers - cov保护性免疫相关的中和抗体反应滴度呈正相关。我们的研究结果不仅表明这种独特的组合佐剂RBD疫苗方案提高了RBD的免疫原性，而且还指出了利用组合佐剂诱导协同保护性免疫反应的重要性。
Vaccination is one of the most successful strategies to prevent human infectious diseases. Combinatorial adjuvants have gained increasing interest as they can stimulate multiple immune pathways and enhance the vaccine efficacy of subunit vaccines. We investigated the adjuvanticity of Aluminum (alum) in combination with rASP-1, a protein adjuvant, using the Middle East respiratory syndrome coronavirus MERS-CoV receptor-binding-domain (RBD) vaccine antigen. A highly enhanced anti-MERS-CoV neutralizing antibody response was induced when mice were immunized with rASP-1 and the alum-adjuvanted RBD vaccine in two separate injection sites as compared to mice immunized with RBD + rASP-1 + alum formulated into a single inoculum. The antibodies produced also significantly inhibited the binding of RBD to its cell-associated receptor. Moreover, immunization with rASP-1 co-administered with the alum-adjuvanted RBD vaccine in separate sites resulted in an enhanced frequency of TfH and GC B cells within the draining lymph nodes, both of which were positively associated with the titers of the neutralizing antibody response related to anti-MERS-CoV protective immunity. Our findings not only indicate that this unique combinatorial adjuvanted RBD vaccine regimen improved the immunogenicity of RBD, but also point to the importance of utilizing combinatorial adjuvants for the induction of synergistic protective immune responses.