Back to resultsThe Development of a COVID19 Oral Vaccine Consisting of Bacillus Subtilis Spores
Primary Purpose
COVID-19 Pneumonia
Status
Completed
Phase
Not Applicable
Locations
Hong Kong
Study Type
Interventional
Intervention
Bacillus subtilis
Sponsored by
About this trial
This is an interventional basic science trial for COVID-19 Pneumonia focused on measuring Covid-19, Vaccine Reaction, Bacillus subtilis
Eligibility Criteria
Inclusion Criteria:
- healthy
- age over 25 years
- the outcome of the following examinations should be clinically insignificant: medical and surgical history (hypo-, hypertension, allergy, other diseases, major surgery, micturition, defecation, sleep, illness within the last 4 weeks prior to the start of the trial);
- participant vaccinated with Sinovac over 4 months
- anti-SARS CoV 2 neutralizing antibody is negative in serum.
Exclusion Criteria:
- pregnant women
- history of COVID-19 infection or showing COVID-19 infection symptoms
- having had contact to people with known COVID-19 infection in the last 14 days
- having fever (> 37.4oC in the last 24 hours), dry cough or feeling tired and having aches and pains, nasal congestion, runny nose, sore throat and diarrhea.
- positive real time RT-PCR COVID-19 test.
- persons with autoimmune diseases
- allergic diathesis or any clinically significant allergic disease (i.e. asthma)
- any condition that might impair the immune response
- recent or current immunosuppressive medication
- any other vaccine application 30 days before the first dose
Sites / Locations
- Zentrogene Bioscience Laboratory Ltd
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
generation of neutralizing antibody for unvaccinated participants
neutralizing antibody booster for vaccinated participants
Arm Description
participants received vaccine 1 capsule of 1×10^10 CFU of B. subtilis spore at day 0, 14, and 28 respectively.
participants after 4-month vaccinated with Sinovac received 1 capsule of 1×10^11 CFU of B. subtilis spore
Outcomes
Primary Outcome Measures
Serum Neutralizing Receptor Binding Domain IgG Antibody Concentration
Concentration of neutralizing IgG antibody against receptor binding domain of spike protein in SARS-COV2
Secondary Outcome Measures
Lentirival Pseudovirus Neutralization Assay (Wild Type of SARS-CoV2)
The ability of neutralization against SARS-CoV-2 was tested by an in vitro pseudo-virus neutralization assay. The lentivirus carrying a GFP gene was pseudotyped with the spike protein from a wild type of SARS-CoV-2. The pseudoviruses were then pre-incubated with serially diluted serum samples from orally vaccinated volunteers before being added to A549 lung carcinoma cells expressing human ACE2 and human TMPRSS2. The percentage of infection rate was measured with a fluorescent plate reader by counting GFP-positive cells. The results were fitted with a non-linear regression model. The dilution of the serum sample resulted in a 50% reduction of infection rate is designated as EC50. The results were presented as "NA" when the serum samples failed to neutralize pseudovirus infection.
Lentirival Pseudovirus Neutralization Assay (D614G SARS-COV2 Variant)
The ability of neutralization against SARS-CoV-2 was tested by an in vitro pseudo-virus neutralization assay. The lentivirus carrying a GFP gene was pseudotyped with the spike protein from a D614G variant of SARS-CoV-2. The pseudoviruses were then pre-incubated with serially diluted serum samples from orally vaccinated volunteers before being added to A549 lung carcinoma cells expressing human ACE2 and human TMPRSS2. The percentage of infection rate was measured with a fluorescent plate reader by counting GFP-positive cells. The results were fitted with a non-linear regression model. The dilution of the serum sample resulted in a 50% reduction of infection rate is designated as EC50. The results were presented as "NA" when the serum samples failed to neutralize pseudovirus infection.
Full Information
NCT ID
NCT05057923
First Posted
September 21, 2021
Last Updated
May 30, 2023
Sponsor
DreamTec Research Limited
1. Study Identification
Unique Protocol Identification Number
NCT05057923
Brief Title
The Development of a COVID19 Oral Vaccine Consisting of Bacillus Subtilis Spores
Official Title
The Development of a COVID19 Oral Vaccine Consisting of Bacillus Subtilis Spores Expressing and Displaying the Receptor Binding Domain of Spike Protein of SARS-COV2
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
July 10, 2021 (Actual)
Primary Completion Date
October 20, 2021 (Actual)
Study Completion Date
November 1, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
DreamTec Research Limited
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a study trial to assess the effectiveness of the immune response stimulated by the genetically engineered Bacillus subtilis which express and display Spike protein of the SARS-COV2 on the spore coat.
Detailed Description
Bacillus subtilis is regarded as safe organism by The Food and Drug Administration and it is presented in most food sources. Preliminary experiments have shown that the genetically engineered Bacillus subtilis can express and display receptor binding domain of spike protein of the SARS-COV2 on its spore coat, thus successfully induce the secretion of cytokines of human cells in vitro. Previous experiments also successfully demonstrated that a increased detection of neutralizing IgG and igM levels in mice after oral administrated with the Bacillus subtilis. This suggests that the transgenic spores of Bacillus subtilis have successfully activated the immune system, producing high-affinity neutralizing antibodies and memory B cells. Furthermore, no adverse effects were shown in all the mices. The engineered Bacillus subtilis will be further studied in a human trials through oral administration to test its safety and the immune effect resulted in human bodys.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19 Pneumonia
Keywords
Covid-19, Vaccine Reaction, Bacillus subtilis
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
two parallel experimental groups were designed.
1. the vaccinated volunteers and 2. unvaccinated groups.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
9 (Actual)
8. Arms, Groups, and Interventions
Arm Title
generation of neutralizing antibody for unvaccinated participants
Arm Type
Experimental
Arm Description
participants received vaccine 1 capsule of 1×10^10 CFU of B. subtilis spore at day 0, 14, and 28 respectively.
Arm Title
neutralizing antibody booster for vaccinated participants
Arm Type
Experimental
Arm Description
participants after 4-month vaccinated with Sinovac received 1 capsule of 1×10^11 CFU of B. subtilis spore
Intervention Type
Biological
Intervention Name(s)
Bacillus subtilis
Intervention Description
Bacillus subtilis, a harmless intestinal commensal, has earned in recent years, great reputation as a vaccine production host and delivery vector with advantages such as low cost, safe for human consumption and straightforward administration. The technology team has succeeded engineering Bacillus subtilis with spore coat proteins resembling the proteins of the nucleus and spikes of coronal virus. This product could have a vaccine like activity within the intestinal environment.
Primary Outcome Measure Information:
Title
Serum Neutralizing Receptor Binding Domain IgG Antibody Concentration
Description
Concentration of neutralizing IgG antibody against receptor binding domain of spike protein in SARS-COV2
Time Frame
Day 0, 27, 42 post oral administration
Secondary Outcome Measure Information:
Title
Lentirival Pseudovirus Neutralization Assay (Wild Type of SARS-CoV2)
Description
The ability of neutralization against SARS-CoV-2 was tested by an in vitro pseudo-virus neutralization assay. The lentivirus carrying a GFP gene was pseudotyped with the spike protein from a wild type of SARS-CoV-2. The pseudoviruses were then pre-incubated with serially diluted serum samples from orally vaccinated volunteers before being added to A549 lung carcinoma cells expressing human ACE2 and human TMPRSS2. The percentage of infection rate was measured with a fluorescent plate reader by counting GFP-positive cells. The results were fitted with a non-linear regression model. The dilution of the serum sample resulted in a 50% reduction of infection rate is designated as EC50. The results were presented as "NA" when the serum samples failed to neutralize pseudovirus infection.
Time Frame
Day 0, 27, 42 post oral administration
Title
Lentirival Pseudovirus Neutralization Assay (D614G SARS-COV2 Variant)
Description
The ability of neutralization against SARS-CoV-2 was tested by an in vitro pseudo-virus neutralization assay. The lentivirus carrying a GFP gene was pseudotyped with the spike protein from a D614G variant of SARS-CoV-2. The pseudoviruses were then pre-incubated with serially diluted serum samples from orally vaccinated volunteers before being added to A549 lung carcinoma cells expressing human ACE2 and human TMPRSS2. The percentage of infection rate was measured with a fluorescent plate reader by counting GFP-positive cells. The results were fitted with a non-linear regression model. The dilution of the serum sample resulted in a 50% reduction of infection rate is designated as EC50. The results were presented as "NA" when the serum samples failed to neutralize pseudovirus infection.
Time Frame
Day 0, 27, 42 post oral administration
10. Eligibility
Sex
All
Minimum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
healthy
age over 25 years
the outcome of the following examinations should be clinically insignificant: medical and surgical history (hypo-, hypertension, allergy, other diseases, major surgery, micturition, defecation, sleep, illness within the last 4 weeks prior to the start of the trial);
participant vaccinated with Sinovac over 4 months
anti-SARS CoV 2 neutralizing antibody is negative in serum.
Exclusion Criteria:
pregnant women
history of COVID-19 infection or showing COVID-19 infection symptoms
having had contact to people with known COVID-19 infection in the last 14 days
having fever (> 37.4oC in the last 24 hours), dry cough or feeling tired and having aches and pains, nasal congestion, runny nose, sore throat and diarrhea.
positive real time RT-PCR COVID-19 test.
persons with autoimmune diseases
allergic diathesis or any clinically significant allergic disease (i.e. asthma)
any condition that might impair the immune response
recent or current immunosuppressive medication
any other vaccine application 30 days before the first dose
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
WAI YEUNG KWONG, PhD
Organizational Affiliation
DreamTec Research Limited
Official's Role
Principal Investigator
Facility Information:
Facility Name
Zentrogene Bioscience Laboratory Ltd
City
Hong Kong
Country
Hong Kong
12. IPD Sharing Statement
Learn more about this trial
The Development of a COVID19 Oral Vaccine Consisting of Bacillus Subtilis Spores
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