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.

自2020年初以来，严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）引发了新型冠状病毒肺炎（COVID-19）全球大流行。截至2022年1月，SARS-CoV-2的全球传播已造成约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，完成标准两剂次疫苗接种后数月，针对免疫原的抗体水平会显著下降，因此推荐接种第三剂或第四剂同源免疫原加强针，以提升抗体应答水平。本研究报道了一种超高效鼻内疫苗加强针，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刺突蛋白受体结合域（可选用野生型或奥密克戎毒株序列）构成。在无需佐剂的情况下，对已完成基础免疫的小鼠单次鼻内接种该加强疫苗，即可显著诱导系统性与黏膜抗体应答：分别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）的生成增加。最为关键的是，单剂次奥密克戎株鼻内加强疫苗可强效提升针对活SARS-CoV-2奥密克戎毒株感染的中和活性。综上，该鼻内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，其临床应用价值值得进一步开展人体临床试验。