Discussion
infection, NAbs
ADENOVIRUS, INFECTION, DECAY
The aerosolized Ad5-nCoV is the first aerosolized COVID-19 vaccine administrated by oral inhalation authorized for emergency use as a booster dose following the primary series of inactivated COVID-19 vaccines. The initial study reported previously indicated that the heterologous aerosolized Ad5-nCoV plus two-dose CoronaVac was more immunogenic than three-dose CoronaVac within 28 days post-vaccination in Chinese adults aged 18 years and older [Although the quick waning of NAbs along with time has been found after the primary or boosting immunization with all kinds of COVID-19 vaccines, the decay rates of neutralizing response associated with different COVID-19 vaccines could be varied [Since considerable escape of the omicron variants to NAb induced by the first generation of COVID-19 vaccine against the prototype strain has been wildly reported [In this study, our data firstly demonstrated the NAb responses against omicron variants persisted for at least 12 months produced by orally administered aerosolised Ad5-nCoV following two-dose CoronaVac priming. NAbs have been proven to be highly predictive of SARS-CoV-2 immune protection [Previously, an increased risk of the rare and potentially fatal thrombosis with thrombocytopenia syndrome has been found associated with recipients of the adenovirus viral vector vaccine (ChAdOx1 nCoV-19) [This study had several limitations. Firstly, mucosal immune responses were not provided because no saliva or mucosal immunity samples were collected per protocol. Secondly, vaccine efficacy or vaccine effectiveness against SARS-CoV-2 was not presented because of no widespread COVID-19 outbreak during the study period. Additionally, the influencing factors of antibody persistence had not been analysed due to the small sample size. However, previous studies found that prior infection and age influence the magnitude and persistence of antibody responses [Recently, low-dose aerosolized Ad5-nCoV at 0.1 mL has been authorized for emergency use as a booster in China and has initiated the deployment of massive vaccination campaign. Each aerosolized Ad5-nCoV vaccination uses only one-fifth intramuscular injection dose of the originally licensed Ad5-nCoV, which is significantly beneficial for addressing the challenge that limited resource in vaccine distribution in many parts of the world needs to be addressed to improve global access to the COVID-19 vaccines. In addition, compared to the intramuscular COVID-19 vaccines, the aerosolized Ad5-nCoV is supposed to be able to elicit respiratory mucosal immunity, which could potentially provide additional protection by eliciting innate and adaptive immunity in the mucosal tissue [In conclusion, our study demonstrated that heterologous orally aerosolised Ad5-nCoV as a booster following two-dose CoronaVac priming had a good long-term safety profile and was persistently more immunogenic than three-dose CoronaVac within 12 months after boosting, providing additional support for the massive COVID-19 vaccine boosting campaign.