Comparing the protection of heterologous booster of inhaled Ad5-nCoV vaccine and hybrid immunity against Omicron BA.5 infection: a cohort study of hospital staff in China

Background: After the exit "zero-COVID" strategy in mainland China by the end of 2022, a large-scale COVID-19 outbreak seeded by Omicron variants occurred. An inhaled adenovirus type-5 vector-based (i.e., inhaled Ad5-nCoV) COVID-19 vaccine was licensed earlier in 2021. In this study, we aimed to assess the real-world effectiveness of a heterologous booster of inhaled Ad5-nCoV vaccine against Omicron infection and compared with the protection from hybrid immunity (i.e., prior breakthrough infection).

Methods: In this retrospective cohort study, we identified 1087 out of a total of 1146 hospital staff from a tertiary hospital in Urumqi city, China from November 22 to December 29, 2022. Demographic characteristics, baseline health status, occupation, behavioral factors, laboratory test of serological IgG antibody, and timeline from immunization to laboratory-testing outcome were obtained. We analysed the individual-level vaccination status of inhaled Ad5-nCoV vaccine, prior SARS-CoV-2 infection status and baseline vaccination status, and other risk factors before follow-up. The protective effects of the heterologous inhaled Ad5-nCoV vaccine and hybrid immunity against Omicron BA.5 infection and hospitalization were calculated as relative rate reduction (RRR), which was estimated using multivariate Poisson regression models.

Results: A total of 1087 hospital staff (median age of 34 years, and 343 males [31.6%]), including 931 accepted for serological antibody tests, were recruited to assess the vaccine effectiveness (VE) of the inhaled Ad5-nCoV booster and hybrid immunity. Among the 1087 participants, 413 had a history of prior SARS-CoV-2 infection (before follow-up) but did not receive an inhaled Ad5-nCoV booster, and 674 reported no prior infection, including 390 who received an inhaled Ad5-nCoV booster. The highest serological IgG antibody level was detected among the inhaled Ad5-nCoV group, with a median of 294.59 S/CO, followed by the hybrid immunity group, with a median of 93.65 S/CO compared to the reference level of the inactivated vaccine group (most of whom received the Sinopharm/BBIBP-CorV vaccine). The inhaled Ad5-nCoV booster and hybrid immunity yielded RRRs of 41.9% (95% CI: 24.8, 55.0) and 97.9% (95% CI: 94.2, 99.2), respectively, against Omicron BA.5 infection, regardless of symptom status.

Conclusion: We found that hybrid immunity could provide a high level of protection against Omicron infection, while a heterologous inhaled Ad5-nCoV booster conferred a moderate level of protection. Our findings supported the rollout of a heterologous vaccination strategy regardless of preexisting vaccine coverage.