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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| generation of neutralizing antibody for unvaccinated participants | Experimental | participants received vaccine 1 capsule of 1×10^10 CFU of B. subtilis spore at day 0, 14, and 28 respectively. |
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| neutralizing antibody booster for vaccinated participants | Experimental | participants after 4-month vaccinated with Sinovac received 1 capsule of 1×10^11 CFU of B. subtilis spore |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bacillus subtilis | Biological | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Serum Neutralizing Receptor Binding Domain IgG Antibody Concentration | Concentration of neutralizing IgG antibody against receptor binding domain of spike protein in SARS-COV2 | Day 0, 27, 42 post oral administration |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| WAI YEUNG KWONG, PhD | DreamTec Research Limited | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Zentrogene Bioscience Laboratory Ltd | Hong Kong | Hong Kong |
6 unvaccinated participants were recruited and their level of serum neutralizing antibody against spike protein of SARS-CoV2 were lower than 0.003 ug/ml.
Participants voluntary enrolled or recruitted by Genfortune Pharmaceuticals Limited
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| ID | Title | Description |
|---|---|---|
| FG000 | Generation of Neutralizing Antibody for Unvaccinated Participants | participants received vaccine 1 capsule of 1×10^10 CFU of B. subtilis spore at day 0, 14, and 28 respectively. Bacillus subtilis: 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
The baseline population does not differ from the participant flow.
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| ID | Title | Description |
|---|---|---|
| BG000 | Generation of Neutralizing Antibody for Unvaccinated Participants | participants received vaccine 1 capsule of 1×10^10 CFU of B. subtilis spore at day 0, 14, and 28 respectively. Bacillus subtilis: 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. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Serum Neutralizing Receptor Binding Domain IgG Antibody Concentration | Concentration of neutralizing IgG antibody against receptor binding domain of spike protein in SARS-COV2 | Participants were orally administered 5x10^7 spores/kg person of recombinant B. subtilis spores mixed with sodium alginate in enteric coated capsules at day 1, 14, and 28. Furthermore, 5 mL of blood samples were drawn at day 0, 27, 42, and the serum samples were analyzed. The titer of neutralizing antibodies was determined with a CLIA-based assay. | Posted | Mean | Standard Deviation | ug/ml | Day 0, 27, 42 post oral administration |
|
Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 30 post-final vaccination.
All AEs were presented.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Generation of Neutralizing Antibody for Unvaccinated Participants | participants received vaccine 1 capsule of 1×10^10 CFU of B. subtilis spore at day 0, 14, and 28 respectively. Bacillus subtilis: 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. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Keith Kwong | DreamTec Research Limited | +85237052355 | keithkwong@dreamtec.hk |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP_ICF | Yes | Yes | Yes | Study Protocol, Statistical Analysis Plan, and Informed Consent Form | Jun 1, 2021 | May 30, 2023 | Prot_SAP_ICF_002.pdf |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
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two parallel experimental groups were designed.
1. the vaccinated volunteers and 2. unvaccinated groups.
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|
| Day 0, 27, 42 post oral administration |
| 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. | Day 0, 27, 42 post oral administration |
| Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Secondary | 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. | Posted | Mean | Standard Deviation | Fold of dilution | Day 0, 27, 42 post oral administration |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | fold dilution | Day 0, 27, 42 post oral administration |
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| 0 |
| 6 |
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| 6 |
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| 6 |
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| D014777 |
| Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| EC50 of Day 42 Serum diltuion in Pseudovirus inhibition assay |
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| EC50 of Day 42 Serum diltuion in Pseudovirus inhibition assay |
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