A nasal omicron vaccine booster elicits potent neutralizing antibody response against emerging SARS-CoV-2 variants

SARS-CoV-2 has caused the COVID-19 pandemic since early 2020. As of January 2022, the worldwide spreading of SARS-CoV-2 leads to approximately 0.35 billion of human infections and five millions of deaths. Current vaccination is one of the effective ways to control SARS-CoV-2 transmission and reduce the disease severity. However, the antibody level against the immunogen significantly drops several months after the standard two-dose vaccination, and hence a third or fourth dose booster (the same immunogen) has been suggested to boost the antibody response. Here, we described an ultra-effective nasal vaccine booster that potently induced the extraordinary high-level of neutralizing antibody in pre-vaccinated mice. The vaccine booster is composed of a recombinant receptor binding domain of SARS-CoV-2 spike (either wild-type or omicron) fused with a domain of SARS-CoV-2 nucleoprotein. In the absence of adjuvants, a single intranasal administration of the booster in pre-vaccinated mice significantly induced systemic and mucosal antibody responses as evidenced by the elevation of the cross-variant neutralizing antibody and induction of IgA in bronchoalveolar lavage respectively. Most importantly, the single dose nasal vaccine booster (omicron version) potently enhanced the neutralizing activity against authentic SARS-CoV-2 omicron virus infection. Taken together, the induction of respiratory mucosal immunity and the enhancement of cross-variant neutralizing activity by the nasal vaccine booster warrants further clinical trials in humans.

严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）自2020年初以来引发了新型冠状病毒肺炎（COVID-19）大流行。截至2022年1月，全球范围内的SARS-CoV-2传播已造成约3.5亿人感染、500万人死亡。当前疫苗接种是控制SARS-CoV-2传播、降低疾病重症程度的有效手段之一。然而，完成标准两剂疫苗接种后的数月内，针对疫苗免疫原的抗体水平会显著下降，因此有建议提出需接种第三剂或第四剂同源加强针（使用相同免疫原）以提升抗体应答水平。
本文描述了一种超高效的鼻腔加强疫苗，该疫苗可在已完成基础免疫的小鼠体内强效诱导极高水平的中和抗体。该加强疫苗由融合了SARS-CoV-2核蛋白结构域的重组SARS-CoV-2刺突蛋白受体结合域（野生型或奥密克戎亚型）构成。在不使用佐剂的情况下，对已完成基础免疫的小鼠单次鼻腔接种该加强疫苗，即可显著诱导系统性与黏膜抗体应答：具体表现为交叉变异株中和抗体水平升高，以及支气管肺泡灌洗液中免疫球蛋白A（IgA）的诱导生成。最为关键的是，单剂奥密克戎亚型鼻腔加强疫苗可强效提升针对真实SARS-CoV-2奥密克戎毒株感染的中和活性。
综上，该鼻腔加强疫苗可诱导呼吸道黏膜免疫并增强交叉变异株中和活性，这一特性支持其开展进一步的人体临床试验。