Trial Outcomes & Findings for The Development of a COVID19 Oral Vaccine Consisting of Bacillus Subtilis Spores (NCT NCT05057923)

NCT ID: NCT05057923

Last Updated: 2023-05-31

Results Overview

Concentration of neutralizing IgG antibody against receptor binding domain of spike protein in SARS-COV2

Recruitment status

COMPLETED

Study phase

Target enrollment

9 participants

Primary outcome timeframe

Day 0, 27, 42 post oral administration

Results posted on

2023-05-31

Participant Flow

Participants voluntary enrolled or recruitted by Genfortune Pharmaceuticals Limited

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.

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	6
Overall Study COMPLETED	6
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Generation of Neutralizing Antibody for Unvaccinated Participants n=6 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.
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=93 Participants
Age, Categorical >=65 years	2 Participants n=93 Participants
Sex: Female, Male Female	3 Participants n=93 Participants
Sex: Female, Male Male	3 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	6 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants
Race (NIH/OMB) White	0 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Region of Enrollment East Asia	6 participants n=93 Participants

PRIMARY outcome

Timeframe: Day 0, 27, 42 post oral administration

Population: 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.

Concentration of neutralizing IgG antibody against receptor binding domain of spike protein in SARS-COV2

Outcome measures

Outcome measures
Measure	Generation of Neutralizing Antibody for Unvaccinated Participants n=6 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.
Serum Neutralizing Receptor Binding Domain IgG Antibody Concentration Day 42	35.8 ug/ml Standard Deviation 8.8
Serum Neutralizing Receptor Binding Domain IgG Antibody Concentration Day 0	0.2 ug/ml Standard Deviation 0.1
Serum Neutralizing Receptor Binding Domain IgG Antibody Concentration Day 27	9.3 ug/ml Standard Deviation 5.4

SECONDARY outcome

Timeframe: Day 0, 27, 42 post oral administration

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.

Outcome measures

Outcome measures
Measure	Generation of Neutralizing Antibody for Unvaccinated Participants n=6 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.
Lentirival Pseudovirus Neutralization Assay (Wild Type of SARS-CoV2) EC50 of Day 27 Serum diltuion in Pseudovirus inhibition assay	NA Fold of dilution Standard Deviation NA 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 (Wild Type of SARS-CoV2) EC50 of Day 0 Serum diltuion in Pseudovirus inhibition assay	NA Fold of dilution Standard Deviation NA 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 (Wild Type of SARS-CoV2) EC50 of Day 42 Serum diltuion in Pseudovirus inhibition assay	76.33 Fold of dilution Standard Deviation 38.7

SECONDARY outcome

Timeframe: Day 0, 27, 42 post oral administration

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.

Outcome measures

Outcome measures
Measure	Generation of Neutralizing Antibody for Unvaccinated Participants n=6 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.
Lentirival Pseudovirus Neutralization Assay (D614G SARS-COV2 Variant) EC50 of Day 27 Serum diltuion in Pseudovirus inhibition assay	NA fold dilution Standard Deviation NA 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) EC50 of Day 0 Serum diltuion in Pseudovirus inhibition assay	NA fold dilution Standard Deviation NA 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) EC50 of Day 42 Serum diltuion in Pseudovirus inhibition assay	82.4 fold dilution Standard Deviation 29.2

Adverse Events

Generation of Neutralizing Antibody for Unvaccinated Participants

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Keith Kwong

DreamTec Research Limited

Phone: +85237052355

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place