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Safety and Immunogenicity of Heterologous and Homologous Boosting with Orally Aerosolized or Intramuscular Ad5-nCoV and Inactivated Vaccines in Children and Adolescents: A Randomized, Open-Label, Parallel Controlled, Single-Center Study

20 Pages Posted: 20 Dec 2022

See all articles by Tao Huang

Tao Huang

Hunan Provincial Center for Disease Control and Prevention

Sheng Zhang

Government of the People's Republic of China - Beijing Key Laboratory of Pediatric Organ Failure

De-Fang Dai

Hunan Provincial Center for Disease Control and Prevention

Bu-Sen Wang

Academy of Military Medical Sciences - Institute of Biotechnology

Lu Zhuang

Government of the People's Republic of China - Beijing Key Laboratory of Pediatric Organ Failure

Hai-Tao Huang

CanSino Biologics Inc.

Zhongfang Wang

Guangzhou Medical University - State Key Laboratory of Respiratory Disease

Jun-Shi Zhao

Hunan Provincial Center for Disease Control and Prevention

Qiu-Ping Li

Government of the People's Republic of China - Beijing Key Laboratory of Pediatric Organ Failure

Shi-Po Wu

Academy of Military Medical Sciences - Institute of Biotechnology

Xue Wang

CanSino Biologics Inc.

Wen-Dan Zhang

Government of the People's Republic of China - Beijing Key Laboratory of Pediatric Organ Failure

Zheng-Hao Zhao

Beijing Institute of Biotechnology

Hao Li

CanSino Biologics Inc.

Jin-Bo Gou

CanSino Biologics Inc.

Li-Hua Hou

Academy of Military Medical Sciences - Institute of Biotechnology

Li-Dong Gao

Hunan Provincial Center for Disease Control and Prevention

Zhi-Chun Feng

Southern Medical University - Neonatal Intensive Care Unit

More...

Abstract

Background: Heterologous booster immunization with orally administered aerosolized Ad5-nCoV has been proven to be safe and highly immunogenic in adults. Here, we aimed to assess the safety and immunogenicity of heterologous booster immunization with orally administered aerosolized Ad5-nCoV in children and adolescents aged 6–17 years who had received two doses of inactivated vaccine.

Methods: We performed a randomized, open-label, parallel-controlled study to assess the safety and immunogenicity of heterologous booster immunization with aerosolized (0.1 ml) or intramuscular Ad5-nCoV (0.3 ml) and homologous booster immunization with inactivated vaccines (ICVs) in children 6–12 years of age and adolescents 13–17 years of age who received two doses of inactivated vaccines (ICVs) > 3 months earlier. Adverse events within 28 days after the booster vaccination were used as the primary outcome for safety evaluation. Plasma neutralizing antibodies (NAbs) on day 28 after the booster were used as the primary endpoint for immunogenicity. This study was registered at ClinicalTrial.gov, NCT05330871.

Findings: Between April 17 and May 28, 436 participants were screened and 360 were enrolled. Of them, 180 were children, and 180 were adolescents. Overall vaccine-related adverse events (VRAEs) were reported in 19.55% (43/220) of aerosolized Ad5-nCoV, 51.43% (36/70) of intramuscular Ad5-nCoV, and 21.43% (15/70) of ICV within 28 days after immunization. Heterologous and homologous booster vaccination elicited a significantly increased neutralizing antibody (NAb) response compared to the antibody response before vaccination on day 28 after booster vaccination. The GMTs of NAb in aerosolized or intramuscular Ad5-nCoV participants were significantly higher than the GMTs in ICV-boosted participants. Heterologous and homologous booster vaccination elicited a limited IFN-γ-secreting T-cell response in children. Heterologous aerosolized Ad5-nCoV boosted the IFN-γ-secreting T-cell response in adolescents.

Interpretation: Our study shows that a heterologous booster with aerosolized Ad5-nCoV is safe and highly immunogenic in children and adolescents.

Trial Registration Details: ClinicalTrial.gov, NCT05330871.

Funding Information: This work was funded by National Key R&D Program of China, No.2021YFC0866200. CanSino Biologics provided investigational vaccines and Continuous Vapouring System for this study. We would like to thank Maijuan Ma of the Beijing Institute of Microbiology and Epidemiology for his useful feedback that improved this paper.

Declaration of Interests: J-BG, H-TH, XW and HL are employees of CanSino Biologics. All the other authors declare no competing interests.

Ethics Considerations: The study protocol and informed consent were reviewed and approved by the Ethical Committee of PLA Army General Hospital and Hunan Provincial Center for Disease Control and Prevention, China (S2021-001-03). Written informed consent was obtained from the children's and adolescents' parents or guardians.

Keywords: COVID-19 vaccine, mucosal vaccine, children, adolescents, clinical trial

Suggested Citation

Huang, Tao and Zhang, Sheng and Dai, De-Fang and Wang, Bu-Sen and Zhuang, Lu and Huang, Hai-Tao and Wang, Zhongfang and Zhao, Jun-Shi and Li, Qiu-Ping and Wu, Shi-Po and Wang, Xue and Zhang, Wen-Dan and Zhao, Zheng-Hao and Li, Hao and Gou, Jin-Bo and Hou, Li-Hua and Gao, Li-Dong and Feng, Zhi-Chun, Safety and Immunogenicity of Heterologous and Homologous Boosting with Orally Aerosolized or Intramuscular Ad5-nCoV and Inactivated Vaccines in Children and Adolescents: A Randomized, Open-Label, Parallel Controlled, Single-Center Study. Available at SSRN: https://ssrn.com/abstract=4304747 or http://dx.doi.org/10.2139/ssrn.4304747

Tao Huang

Hunan Provincial Center for Disease Control and Prevention ( email )

Sheng Zhang

Government of the People's Republic of China - Beijing Key Laboratory of Pediatric Organ Failure ( email )

De-Fang Dai

Hunan Provincial Center for Disease Control and Prevention ( email )

Changsha
China

Bu-Sen Wang

Academy of Military Medical Sciences - Institute of Biotechnology ( email )

Lu Zhuang

Government of the People's Republic of China - Beijing Key Laboratory of Pediatric Organ Failure ( email )

Hai-Tao Huang

CanSino Biologics Inc. ( email )

Tianjin
China

Zhongfang Wang

Guangzhou Medical University - State Key Laboratory of Respiratory Disease ( email )

Guangzhou, Guangdong
China

Jun-Shi Zhao

Hunan Provincial Center for Disease Control and Prevention ( email )

Changsha
China

Qiu-Ping Li

Government of the People's Republic of China - Beijing Key Laboratory of Pediatric Organ Failure ( email )

Shi-Po Wu

Academy of Military Medical Sciences - Institute of Biotechnology ( email )

Beijing
China

Xue Wang

CanSino Biologics Inc. ( email )

Tianjin
China

Wen-Dan Zhang

Government of the People's Republic of China - Beijing Key Laboratory of Pediatric Organ Failure ( email )

Zheng-Hao Zhao

Beijing Institute of Biotechnology ( email )

Beijing
China

Hao Li

CanSino Biologics Inc. ( email )

Jin-Bo Gou

CanSino Biologics Inc. ( email )

Tianjin
China

Li-Hua Hou

Academy of Military Medical Sciences - Institute of Biotechnology ( email )

Beijing
China

Li-Dong Gao

Hunan Provincial Center for Disease Control and Prevention ( email )

Changsha
China

Zhi-Chun Feng (Contact Author)

Southern Medical University - Neonatal Intensive Care Unit

Beijing
China

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