Heterologous Boost Immunization With Ad5-nCoV After Three-dose Priming With an Inactivated SARS-CoV-2 Vaccine
Study Details
Study Description
Brief Summary
This is an open-label, randomized, parallel-controlled clinical trial to evaluate the safety and immunogenicity of heterologous prime-boost immunization with an aerosolized (Ad5-nCoV-IH) or intramuscular (Ad5-nCoV-IM) Ad5-nCoV after three-dose priming with an inactivated COVID-19 vaccine (CoronaVac) in adults aged 18 years and above. A total of 360 subjects will be included. Approximately 210 subjects who have completed three doses of CoronaVac more than 6 months ago in the prior clinical trial and other 150 eligible subjects will be recruited and randomized respectively in a ratio of 1:1:1 to receive a booster dose of Ad5-nCoV-IH or Ad5-nCoV-IM or ICV. The occurrence of adverse reactions within 28 days and serious adverse events within 6 months after vaccination will be observed in all participants. In addition, blood and saliva samples will be collected from all participants on the day 0 before and 14, 28 days and 3, 6 months after the booster vaccination. Each subject will remain in this study for approximately 6 months.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 4 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Group A Approximately 70 subjects recruited from the prior clinical trial and newly enrolled 50 subjects will receive a booster dose of aerosolized Ad5-nCoV after three-dose priming with ICV |
Biological: Ad5-nCoV-IH
The orally aerosolized Ad5-nCoV is a replication defective Ad5 vectored COVID-19 vaccine expressing the full-length spike gene of wide-type SARS-CoV-2, Wuhan-Hu-1. The Ad5-nCoV vaccine was supplied in 1.5mL/vial, at a concentration of 1.0 × 1011 viral particles per mL as a liquid formulation. 0.1 ml of Ad5-nCoV vaccine will be aerosolized by using Continuous Vapouring System. Then, the aerosolized droplets will be poured into a disposable suction cup and be inhaled by participants through mouth.
Other Names:
|
Experimental: Group B Approximately 70 subjects recruited from the prior clinical trial and newly enrolled 50 subjects will receive a booster dose of intramuscular Ad5-nCoV after three-dose priming with CoronaVac |
Biological: Ad5-nCoV-IM
The Ad5-nCoV is a replication defective Ad5 vectored COVID-19 vaccine expressing the full-length spike gene of wide-type SARS-CoV-2, Wuhan-Hu-1. It was supplied in 1·5mL/vial, at a concentration of 1.0 × 1011 viral particles per mL as a liquid formulation. Participants will be administrated 0.5ml(5×1010VP)of Ad5-nCoV vaccine intramuscularly.
Other Names:
|
Experimental: Group C Approximately 70 subjects recruited from the prior clinical trial and newly enrolled 50 subjects will receive homologous fourth dose of CoronaVac. |
Biological: CoronaVac
CoronaVac is an inactivated whole-virion vaccine with aluminium hydroxide as the adjuvant, prepared with a novel coronavirus (CZ02 strain) inoculated in African green monkey kidney cells (Vero cells). One dose of CoronaVac contains 3 μg of SARS-CoV-2 virion in a 0.5 mL aqueous suspension for injection with 0.45 mg/mL of aluminium.
|
Outcome Measures
Primary Outcome Measures
- Incidence of adverse reactions within 28 days after the booster dose [Within 28 days the booster dose]
Incidence of adverse reactions within 28 days after the booster dose.
- GMT of neutralizing antibodies against live SARS-CoV-2 virus on day 28 after the booster dose. [On day 28 after the booster dose]
GMT of neutralizing antibodies against live SARS-CoV-2 virus on day 28 after the booster dose.
Secondary Outcome Measures
- Geometric Mean Fold Increase (GMI) and seroconversion of neutralizing antibodies against live SARS-CoV-2 virus on day 28 after the booster dose. [On day 28 after the boost vaccination]
GMI and seroconversion of neutralizing antibodies against live SARS-CoV-2 virus on day 28 after the booster dose in immunogenicity cohort.
- GMT, GMI and seroconversion of neutralizing antibodies against live SARS-CoV-2 virus on day 14, month 3 and 6 after the booster dose. [On day 14, month 3 and 6 after the booster dose]
GMT, GMI and seroconversion of neutralizing antibodies against live SARS-CoV-2 virus as compared to baseline on day 14, month 3 and 6 after the booster dose.
- Geometric mean concentration (GMC), GMI and seroconversion of anti-SARS-CoV-2 NP-specific, RBD-specific and NTD-specific IgG measured by ELISA on day 14, day 28 and month 3 and 6 after the booster dose. [On day 14, day 28 and month 3 and 6 after the booster dose]
Geometric mean concentration (GMC), GMI and seroconversion of anti-SARS-CoV-2 NP-specific, RBD-specific and NTD-specific IgG measured by ELISA on day 14, day 28 and month 3 and 6 after the booster dose.
- Incidence of adverse reactions within 30 minutes after the booster dose. [Within 30 minutes after the booster dose]
Incidence of adverse reactions within 30 minutes after the booster dose.
- Incidence of adverse reactions within 14 days after the booster dose. [Within 14 days after the booster dose]
Incidence of adverse reactions within 14 days after the booster dose.
- Incidence of adverse events within 28 days after the booster dose. [Within 28 days after the booster dose]
Incidence of adverse events within 28 days after the booster dose.
- Incidence of serious adverse events (SAE) until 6 months after the booster dose. [Within 6 months after the booster dose]
Incidence of SAE until 6 months after booster vaccination.
Other Outcome Measures
- GMT, GMI and seroconversion of neutralizing antibodies against VOC/VOI of SARS-CoV-2 virus on day 28 after the booster dose. [On day 28 after the booster dose]
GMT, GMI and seroconversion of neutralizing antibodies against VOC/VOI of SARS-CoV-2 virus on day 28 after the booster dose.
- The levels of IFN-γ、TNF-α、IL-2 secreted by specific T cells stimulated with a peptide pool covering the full-length spike glycoprotein on day 14 after the booster vaccination. [On day 14 after the booster vaccination]
The levels of IFN-γ、TNF-α、IL-2 secreted by specific T cells stimulated with a peptide pool covering the full-length spike glycoprotein on day 14 after the booster vaccination.
- The levels of anti-SARS-CoV-2 RBD-specific binding IgA in saliva on day 14, day 28 and month 3 and 6 after the booster dose. [On day 28 after the booster dose]
The levels of anti-SARS-CoV-2 RBD-specific binding IgA in saliva on day 14, day 28 and month 3 and 6 after the booster dose.
- GMT and GMI of neutralizing antibodies against live SARS-CoV-2 virus on day 28 after the booster dose stratified by age (aged 18-59 years and over 60 years). [On day 28 after the booster dose]
GMT and GMI of neutralizing antibodies against live SARS-CoV-2 virus on day 28 after the booster dose stratified by age (aged 18-59 years and over 60 years).
- The levels of anti-SARS-CoV-2 N protein binding IgG on day 14 after the booster dose. [On day 14 after the booster dose]
The levels of anti-SARS-CoV-2 N protein binding IgG on day 14 after the booster dose.
- The GMT of neutralizing antibodies against the Ad5 before vaccination and any exploratory analyses of other indicators stratified by pre-existing anti-Ad5 NAb titres at baseline(>1:200,≤1:200) [On day 0 before the booster dose]
The GMT of neutralizing antibodies against the Ad5 before vaccination and any exploratory analyses of other indicators stratified by pre-existing anti-Ad5 NAb titres at baseline(>1:200,≤1:200)
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Health subjects aged ≥18 years
-
The subject can provide with informed consent and sign informed consent form (ICF).
-
The subjects are able to and willing to comply with the requirements of the clinical trial program and could complete the 6-month follow-up of the study.
-
Participants who have received three-dose of inactivated SARS-CoV-2 vaccine more than 6 months ago.
Exclusion Criteria:
-
Have the medical history or family history of convulsion, epilepsy, encephalopathy and psychosis.
-
Be allergic to any component of the research vaccines, or used to have a history of hypersensitivity or serious reactions to vaccination.
-
Vaccine-related SAE occurred after previous vaccination with COVID-19 vaccine.
-
Women with positive urine pregnancy test or in lactation.
-
Have acute febrile diseases or infectious diseases or have a history of SARS.
-
Axillary temperature>37.0℃
-
Have serious cardiovascular diseases, such as arrhythmia, conduction block, myocardial infarction, severe hypertension that cannot be controlled by medication (systolic blood pressure ≥180mmHg and/or diastolic blood pressure ≥110mmHg when measured in the field)
-
Have severe chronic diseases or condition is not stable, such as asthma, diabetes, thyroid disease
-
Congenital or acquired angioedema / neuroedema.
-
Have the history of urticaria 1 year before.
-
Have asplenia or functional asplenia.
-
Patients with chronic obstructive pulmonary disease, pulmonary fibrosis and other pulmonary abnormalities.
-
Have history of SARS-CoV-2 infection or COVID-19.
-
Have symptoms of upper respiratory tract infection.
-
Have traveled to medium or high risk areas or traveled abroad in the past 21 days, and epidemiologically contacted with SARS-CoV-2.
-
Any medical, psychological, social, or other conditions that, in the investigator's judgment, are inconsistent with the protocol or affect the subject's informed consent.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Jiangsu Provincial Center for Diseases Control and Prevention | Nanjing | Jiangsu | China |
Sponsors and Collaborators
- Jiangsu Province Centers for Disease Control and Prevention
Investigators
- Principal Investigator: Jingxin Li, PhD, Jiangsu Provincial Center for Diseases Control and Prevention
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- JSVCT153