The protective nasal boosting of a triple-RBD subunit vaccine against SARS-CoV-2 following inactivated virus vaccination
Jingyi Yang, Meiqin Liu, Lin Liu, Xian Li, Mengxin Xu, Haofeng Lin, Min Li, Huimin Yan, Yao-Qing Chen, Zheng‐Li Shi
Abstract
Though COVID-19 vaccines have been developed and clinically deployed rapidly, new variants of concern (VOCs) are still emerging frequently and escalating around the world. More breakthrough infections occurred even vaccination rates are high. For possible ending of the pandemic, curbing infection and stopping transmission are priority. Booster approach with either mRNA or inactivated vaccines can reduce COVID-19 severity, 1 , 2 , 3 but shows limited efficacy against infection and transmission. One of the most important reasons is that serum IgG is hard accessible to mucosal surface of the upper respiratory tract, where the initial infection and replication of SARS-CoV-2 occur. 4 , 5 With ability to generate mucosal immunity against SARS-CoV-2, intranasal immunization has attracted worldwide attention. 6 A most recent report that a combination of systemic mRNA vaccination plus mucosal adenovirus-S immunization induced strong neutralizing antibody responses suggest mucosal booster vaccination is essential to establish robust sterilizing immunity in the respiratory tract against SARS-CoV-2. 7 Recently, an inhaled COVID vaccine named Convidecia Air has been approved for emergency use as a booster in China. 8 We have designed a bivalent chimeric triple-RBD immunogen containing one Delta RBD and two Omicron RBDs (3Ro-NC) 9 (Supplementary Fig. 1 ) and demonstrated that intranasal (i.n) immunization with 3Ro-NC plus recombinant flagellin KFD adjuvant could induce robust systemic and mucosal immunity against SARR-CoV-2 VOCs. It was noted that the mucosal immunity induced by 3Ro-NC plus KFD adjuvant inhibited Omicron infections in both upper and lower respiratory tracts.