**The Motivation Behind the Study**
As the COVID-19 pandemic evolved, so did the virus, with new variants emerging and challenging the effectiveness of existing vaccines. By the end of 2022, China experienced a significant wave of Omicron infections, leading to a large portion of the population developing hybrid immunity. However, questions remained about whether booster doses of vaccines based on the ancestral strain could still provide protection against these new variants. Our study sought to answer this question by comparing the effectiveness of two booster vaccine formulations: one administered via oral inhalation and the other via intramuscular injection.
**The Study Design and Challenges**
This is a multicenter, partially randomized, platform trial aims to evaluate the effectiveness of a booster dose of aerosolized or intramuscular Ad5-nCoV in adults aged 18 years and older predominantly with hybrid immunity against COVID-19. The study was conducted across five cities in Jiangsu Province, China, and involved over 6,000 participants. We randomized participants to receive either the aerosolized or intramuscular booster vaccine, while a control group opted out of the booster but agreed to participate in COVID-19 surveillance. Over a six-month follow-up period, we monitored participants for symptomatic COVID-19 cases and assessed immune responses through blood samples.
One of the key challenges we faced was ensuring consistent follow-up with participants over such a long period. This study would not have been possible without the dedication of our research site staff, who conducted weekly follow-ups with participants for six months. Their commitment to tracking symptoms, collecting data, and ensuring participant compliance was instrumental in the success of this trial. We are deeply grateful for their hard work and perseverance.
**The Findings**
In this trial, we found that boosting with the aerosolized Ad5-nCoV containing the ancestral strain was associated with a lower incidence of symptomatic COVID-19 caused by Omicron variants, despite the majority of the individuals having a hybrid-immune background against COVID-19. Furthermore, our findings suggest that the inhaled version of Ad5-nCoV may confer a numerically greater protection against COVID-19 compared to the intramuscular injected version of Ad5-nCoV (52.3% vs. 37.2%) but not significantly, despite similar cellular and humoral responses were observed across both vaccine groups and 4/5 lower of the dosage of the aerosolized Ad5-nCoV compared to that of the intramuscular Ad5-nCoV. Although aerosolized Ad5-nCoV showed a numerically higher estimated effectiveness than the intramuscular Ad5-nCoV did, there is no solid evidence that the inhaled version of aerosolized Ad5-nCoV is more favorable than an intramuscular injection of Ad5-nCoV.
**The Human Side of the Study**
Beyond the numbers and statistical analyses, this study was a testament to the power of collaboration and community engagement. We are immensely grateful to all the participants who volunteered their time and effort to contribute to this research. Their willingness to undergo regular testing, provide blood samples, and report symptoms over six months was crucial to the success of this study. Without their participation and trust, this research would not have been possible.
We also want to acknowledge the tireless efforts of the research teams at the five study sites. Their dedication to participant follow-up, data collection, and adherence to the study protocol ensured the integrity and reliability of our findings. Conducting a study of this scale during a pandemic was no small feat, and their commitment to public health research is truly.
**Implications for Future Research**
Our findings have important implications for future vaccination strategies, particularly in populations with hybrid immunity. While the aerosolized vaccine showed promise, further research is needed to fully understand the potential advantages of mucosal vaccines in preventing both symptomatic and asymptomatic infections. Additionally, as new variants continue to emerge, it will be crucial to evaluate the effectiveness of updated vaccine formulations.
We hope that our study contributes to the ongoing global effort to combat COVID-19 and informs future vaccination policies. As we continue to navigate the challenges of the pandemic, we remain committed to advancing research that protects public health and improves vaccine accessibility for all.
**Final Thoughts**
This study was a collaborative endeavor that brought together researchers, healthcare workers, and participants from diverse backgrounds. It highlights the importance of teamwork, perseverance, and community engagement in advancing scientific knowledge. We are proud of what we have accomplished together and look forward to continuing our work in the fight against COVID-19.
Thank you to everyone who contributed to this study—your efforts have made a difference.