A novel simian adenovirus-vectored COVID-19 vaccine elicits effective mucosal and systemic immunity in mice by intranasal and intramuscular vaccination regimens

摘要

The failure of COVID-19 vaccines to prevent SARS-CoV-2 infection and transmission, a possibly critical reason was the lack of protective mucosal immunity in the respiratory tract. Here, we evaluated the effects of mucosal and systemic immunity from a novel simian adenovirus-vectored COVID-19 vaccine (Sad23L-nCoV-S) in mice in comparison with Ad5-nCoV-S by intranasal (IN) drip and intramuscular (IM) injection vaccinations. As good as the well-known Ad5-nCoV-S vaccine, a single-dose IN inoculation of 1 x 109 PFU Sad23L-nCoV-S vaccine induced a similar level of IgG S-binding antibody (S-BAb) and neutralizing antibody (NAb) and higher IgA in serum, while IN route raised significantly higher IgG and IgA S-BAb and NAb in bronchoalveolar lavage (BAL), and specific IFN-gamma secreting T-cell response in lung compared with IM route, but lower T-cell response in spleen. By prime-boost vaccination regimens with different combinations of IN and IM inoculations of Sad23L-nCoV-S vaccine, the IN-involved vaccination stimulated higher protective mucosal or local immunity in BAL and lung, while the IM-involved immunization induced higher systemic immunity in serum and spleen. A long-term sustained mucosal and systemic NAb and T- cell immunity to SARS-CoV-2 was maintained at high level over 32 weeks by prime-boost vaccination regimens with IN and IM routes. In conclusion, priming or boosting immunization with IN inoculation of Sad23L-nCoV-S vaccine could induce effective mucosal immunity and in combination of IM route could additionally achieve systemic immunity, which provided an important reference for vaccination regimens against respiratory virus infection.

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