The Development of a COVID19 Oral Vaccine Consisting of Bacillus Subtilis Spores

COVID-19 Pneumonia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05057923
• Other study ID #: PRP/008/21FX
• Status: Completed
• Phase: N/A
• Start date: July 10, 2021
• Est. completion date: November 1, 2021

Study information

• Verified date: May 2023
• Source: DreamTec Research Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: November 1, 2021
• Est. primary completion date: October 20, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 25 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• COVID-19 Pneumonia

Intervention

Biological:
• 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.

Locations

Country	Name	City	State
Hong Kong	Zentrogene Bioscience Laboratory Ltd	Hong Kong

Sponsors (1)

Lead Sponsor	Collaborator
DreamTec Research Limited

Country where clinical trial is conducted

Hong Kong, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
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.	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.	Day 0, 27, 42 post oral administration