The Wilcoxon matched-pairs signed rank test was utilized for within-group comparisons across different time points, and the Mann-Whitney test was applied for between-group comparisons

The Wilcoxon matched-pairs signed rank test was utilized for within-group comparisons across different time points, and the Mann-Whitney test was applied for between-group comparisons. pivotal intervention for reducing disease severity and preventing hospitalizations.1,2Since 2020, numerous vaccines have been developed and deployed worldwide to combat the pandemic. As of March 30, 2023, the World Health Business (WHO) reported 183 COVID-19 vaccines in clinical development and 199 in pre-clinical development. These Hydroxyurea vaccines are based on various platforms, including inactivated computer virus, mRNA, protein subunit, and viral vectored vaccines.3Most approved vaccines are administered via intramuscular injections, which primarily induce serological IgG. However, intramuscular vaccination does not provide a strong first line of defense in the respiratory tract due to a lack of mucosal immunity. This limitation underscores the need for inhalable or intranasal vaccines that mimic the natural entry route of SARS-CoV-2 via the airways.47 To address this issue, several viral vectored vaccines, including those using adenoviruses8or attenuated influenza viruses9for intranasal or inhaled administration, have been approved. Remarkably, clinical studies have exhibited that inhaled vaccines utilizing the adenovirus type 5 vector (Ad5) can generate antibody responses comparable to those induced by intramuscular injections, but at significantly lower doses.8Moreover, the inhaled Ad5 vector COVID-19 vaccine (Ad5-nCoV) has been reported to be safe and capable of inducing higher levels of neutralizing antibodies (nAbs) against the prototype and Omicron BA.5 variant following a sequential vaccination strategy after two doses of Hydroxyurea inactivated vaccines (I-I-A).1012However, the effectiveness of the aerosol Ad5-nCoV as a sequential booster after three doses of inactivated vaccines remains unknown. Additionally, the optimal sequential strategy is still under investigation. In this study, we describe the kinetics of antibody immune responses induced by two different vaccination strategies: a heterologous booster with aerosol Ad5-nCoV vaccine after two (I-I-A) or three (I-I-I-A) doses of inactivated vaccines. We compared the neutralizing antibody responses elicited by the heterologous aerosolized Ad5-nCoV booster to those observed in BA.5 breakthrough infections. Furthermore, we explored the factors contributing to the differences in nAb responses between the I-I-A and I-I-I-A groups. Our findings provide useful insights for selecting effective vaccination strategies and suggest that pre-boost antibody levels could be used to predict the efficacy of booster vaccination. == Materials and methods == == Hydroxyurea Study cohort == The inhaled aerosol Ad5-nCoV vaccines contain a replication-defective adenovirus type 5 (Ad5) vector expressing the full-length spike protein gene of the wild-type SARS-CoV-2, strain Wuhan-Hu-1. To assess efficiency of heterologous booster vaccination following two or three doses of inactivated vaccines, we recruited 35 participants who inhaled an aerosol Ad5-nCoV as booster vaccination, consist of 18 who had finished two doses of inactivated vaccines (I-I-A group; 12 [66.7%] female, 6 [33.3%] male; median age 27 years [22 ~ 49]), and 17 with three doses (I-I-I-A group; 13 [76.5%] female, 4 [23.5%] male; median age 26 years [22 ~ 35]). Additionally, we enrolled 112 patients who had experienced BA.5 breakthrough infections during August 2022 to January 2023, including 33 had received two doses of an inactivated vaccine before the infection (I-I-Bi group; 23 [69.7%] female, 10 [30.3%] male; median age 38 years [4 ~ 89]), Hydroxyurea and 79 had received three doses of an inactivated vaccine before the contamination (I-I-I-Bi group; 37 [46.8%] female, 42 [53.2%] male; median age 51 years [20 ~ 84];Table 1). Plasma samples were collected from each subject at multiple time points. (Physique 1a). == Table 1. == Demographic characteristics. == Physique 1. == Dynamics of nAb responses against SARS-CoV-2 wild-type (WT) strain and omicron subvariants after aerosolized Ad5-nCoV vaccination following two or three doses of inactivated vaccines. (a) Sampling time points. Created with BioRender.com. (b-c) Rabbit Polyclonal to PHACTR4 dynamics of nAb responses of the I-I-A group (b) and the I-I-I-A group (c). The dashed lines represent the detection limit, and the values below the dots stand for the geometric mean of the FRNT50. Wilcoxon matched-pairs signed rank test was performed.