Effectiveness of a booster dose of aerosolized or intramuscular adenovirus type 5 vectored COVID-19 vaccine in adults with hybrid immunity against COVID-19: a multicenter, partially randomized, platform trial in China

BackgroundThe primary objective of this research was to assess if a booster dose with COVID-19 vaccines containing ancestral strain could still provide significant protection against symptomatic SARS-CoV-2 infection in a predominantly hybrid-immune population during the period of omicron variant dominance. MethodsWe did a multicenter, partially randomized, platform trial to evaluate the effectiveness of a booster dose of an aerosolized or intramuscular adenovirus type 5 vectored COVID-19 vaccine (Ad5-nCoV) in adults, after the national-wide omicron circulating at the end of year 2022 in China. Participants who were willing to receive a COVID-19 booster dose were randomly assigned to receive one of the booster doses. While, those participants who refused to take a booster dose but consented to participate COVID-19 surveillance were included in a control group. Both participants receiving a booster dose or not were monitored for symptomatic COVID-19 during a six-month surveillance period. ResultsBetween May 23, 2023, and August 28, 2023, 4089 eligible participants were equally randomized to receive a booster dose of aerosolized Ad5-nCoV through oral inhalation at 0.1mL (IH Ad5-nCoV, n=2039) or intramuscular injection of Ad5-nCoV at 0.5 mL (IM Ad5-nCoV, n=2050). While, 2008 participants were enrolled in the blank-control group. A total of 79 COVID-19 cases were confirmed, with 22 (0.006%) in the IH Ad5-nCoV group, 23 (0.007%) in the IM Ad5-nCoV group, and 34 (0.01%) in the control group. Adjusted effectiveness of IH Ad5-nCoV and IM Ad5-nCoV from 14 days after the vaccination were 51.6% (95% CI 9.0 to 74.3) and 38.1% (95% CI - 9.6 to 65.1), respectively. InterpretationSignificant protection against symptomatic COVID-19 caused by the Omicron variant, during the ongoing pandemic of evolving COVID-19 variants, was found to be provided by boosting with the ancestral strain-containing vaccine IH Ad5-nCoV, but not by boosting with IM Ad5-nCoV.