Abstract
The COVID-19 pandemic has underscored vaccination as a crucial strategy for reducing disease severity and preventing hospitalizations. Heterologous boosters using aerosolized Ad5-nCoV following two doses of inactivated vaccine have demonstrated superior antibody responses. However, the comprehensive dynamics of this antibody boost and the optimal timing for heterologous boosters are still not fully understood. In this study, we investigated the dynamics of neutralizing antibody (nAb) responses in recipients of heterologous booster vaccinations with aerosolized Ad5-nCoV following either two (I-I-A) or three (I-I-I-A) doses of COVID-19 inactivated vaccines. The findings indicate that a booster dose of aerosolized Ad5-nCoV vaccine induced robust and durable nAb responses comparable to those elicited in BA.5 breakthrough infections with similar doses of inactivated vaccine. Notably, group I-I-A showed higher peak nAb titers against the WT strain, BA.5, and XBB.1 variants compared to group I-I-I-A, inversely correlating with the prior nAb levels. This suggesting the possible efficacy of the heterologous aerosolized Ad5-nCoV booster and indicates that pre-boost antibody levels may be related to the outcomes of booster vaccination.