LTB-SA7 Vaccine for Staph Infection

(LTBSA701 Trial)

Overseen By Barbara Hubeli, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: LimmaTech Biologics AG

Must not be taking: Immunosuppressants, Antineoplastics, Chemotherapy, others

Disqualifiers: HIV, Autoimmune disease, Allergy, others

Compensation: Varies

Number of Visits: 2

Duration: 2 months

129 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have taken immunosuppressive drugs, antineoplastic agents, or systemic antibiotics recently. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the LTB-SA7 treatment for Staph infection?

Research on similar multivalent vaccines for Staphylococcus aureus, like Sta-V5 and IBT-V02, shows they can provide strong protection by generating antibodies and immune responses that target multiple components of the bacteria. These findings suggest that a multivalent approach, like LTB-SA7, could also be effective in preventing Staph infections. ^{1 2 3 4 5}

Is the LTB-SA7 vaccine for Staph infection safe for humans?

The SA4Ag vaccine, which is similar to LTB-SA7, has been tested in humans and found to be generally well tolerated, with most side effects being mild. This suggests that the LTB-SA7 vaccine may also be safe for humans. ^{6 7 8 9 10}

How is the LTB-SA7 vaccine different from other treatments for Staph infections?

The LTB-SA7 vaccine is unique because it uses the heat-labile enterotoxin B subunit (LTB) as a component, which is known for its ability to enhance immune responses. This approach is different from traditional treatments that typically involve antibiotics, as it aims to prevent infections by boosting the body's immune system to fight off Staph bacteria. ^{11 12 13 14 15}

What is the purpose of this trial?

In this study, the candidate vaccine LTB-SA7 will be tested for safety and immunogenicity in healthy adults.

Research Team

Nehkonti Adams, MD

Principal Investigator

Naval Medical Research Command

Eligibility Criteria

Healthy adults aged 18-50 who are in good general health as determined by medical history, lab tests, and physical exams. Participants must be willing to follow the study rules and visit schedule. Women of childbearing potential must have a negative pregnancy test and agree to use effective contraception.

Inclusion Criteria

WOCBP must be willing to use a highly effective method of contraception during the trial

Negative urine pregnancy test for women of childbearing potential (WOCBP)

Good general health by medical history, laboratory findings and physical examination as judged by the investigator before receiving the first injection

Exclusion Criteria

I haven't had cancer drugs or immunotherapy in the last 3 months.

History of any chronic or progressive disease that according to judgment of the investigator could interfere with the trial outcomes or pose a threat to the participant's health

Received an investigational or non-registered product (medicinal drug or vaccine), other than the trial vaccine within 3 months prior to 1st administration of trial vaccine, or planned use during the trial period

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the LTB-SA7 vaccine or placebo, with 1 or 2 vaccinations administered 1 month apart

2 months

2 visits (in-person)

Follow-up

Participants are monitored for safety and immunogenicity, including assessment of adverse events and antibody titers

6 months

Multiple visits (in-person and virtual)

Treatment Details

Interventions

• LTB-SA7

Trial Overview The trial is testing LTB-SA7, a new vaccine aimed at preventing Staphylococcus aureus infections. Volunteers will either receive the actual vaccine or a placebo (a harmless substance with no treatment effect) to compare outcomes.

Participant Groups

Group I: LTB-SA7 medium dose, 2 vaccinations Experimental Treatment 1 Intervention

The candidate toxoid vaccine (LTB-SA7) is administered twice, 1 month apart.

Group II: LTB-SA7 medium dose, 1 vaccination Experimental Treatment 1 Intervention

The candidate toxoid vaccine (LTB-SA7) is administered once, 1 month later participant receives a placebo.

Group III: LTB-SA7 low dose, 2 vaccinations Experimental Treatment 1 Intervention

The candidate toxoid vaccine (LTB-SA7) is administered twice, 1 month apart.

Group IV: LTB-SA7 low dose, 1 vaccination Experimental Treatment 1 Intervention

The candidate toxoid vaccine (LTB-SA7) is administered once, 1 month later participant receives a placebo.

Group V: LTB-SA7 high dose, 2 vaccinations Experimental Treatment 1 Intervention

The candidate toxoid vaccine (LTB-SA7) is administered twice, 1 month apart.

Group VI: LTB-SA7 high dose, 1 vaccination Experimental Treatment 1 Intervention

The candidate toxoid vaccine (LTB-SA7) is administered once, 1 month later participant receives a placebo.

Group VII: Placebo Placebo Group 1 Intervention

Participant receives placebo twice, 1 month apart.

Who Is Running the Clinical Trial?

LimmaTech Biologics AG

Lead Sponsor

Trials

9

Recruited

1,500+

Navy Medical Research Command (NMRC)

Collaborator

Trials

1

Recruited

130+

Biomedical Advanced Research and Development Authority

Collaborator

Trials

108

Recruited

574,000+

Wellcome Trust

Collaborator

Trials

236

Recruited

15,770,000+

Findings from Research

The multicomponent toxoid vaccine IBT-V02 shows promising pre-clinical efficacy in preventing acute skin infections caused by Staphylococcus aureus, generating strong neutralizing antibodies against multiple toxins.

Vaccination with IBT-V02 not only protects against initial infections but also provides lasting immunity against secondary infections, highlighting its potential as a preventive measure against S. aureus-related diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IBT-V02: A Multicomponent Toxoid Vaccine Protects Against Primary and Secondary Skin Infections Caused by Staphylococcus aureus. Karauzum, H., Venkatasubramaniam, A., Adhikari, RP., et al.[2021]

The 4-component vaccine targeting secreted toxins from Staphylococcus aureus was found to be safe in non-human primates, even at doses 5 to 10 times higher than what would be proposed for humans, with no adverse clinical signs or significant changes in health parameters.

The vaccine elicited strong immune responses, generating high levels of toxin-specific antibodies and enhancing T cell activity, suggesting it could be a promising next-generation approach for preventing staphylococcal infections if proven effective in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Immunogenicity of a 4-Component Toxoid-Based Staphylococcus aureus Vaccine in Rhesus Macaques. Venkatasubramaniam, A., Liao, G., Cho, E., et al.[2021]

The multivalent vaccine Sta-V5, developed to target methicillin-resistant Staphylococcus aureus (MRSA), provided up to 100% protection in five different murine disease models, indicating its high efficacy against various S. aureus strains.

Sta-V5 not only generates strong antibody responses that help kill the bacteria but also activates T-cell responses, including contributions from γδ T cells, suggesting a comprehensive immune response that could be crucial for effective vaccination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Broad and Effective Protection against Staphylococcus aureus Is Elicited by a Multivalent Vaccine Formulated with Novel Antigens. Deng, J., Wang, X., Zhang, BZ., et al.[2020]

A novel approach to preventing Staphylococcus aureus infections involves developing a vaccine targeting the LukAB leukotoxin, which is present in all clinical isolates and is responsible for killing human immune cells.

Several mutated LukAB toxoids were identified that can elicit strong immune responses, and combining antibodies against LukAB with other toxins can completely neutralize the cytotoxic effects of S. aureus, supporting the idea of a multivalent toxoid vaccine for better protection against these infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rational Design of Toxoid Vaccine Candidates for Staphylococcus aureus Leukocidin AB (LukAB). Kailasan, S., Kort, T., Mukherjee, I., et al.[2021]

The study evaluated a novel vaccine candidate, recombinant ScaF (r-ScaF), which successfully induced strong immune responses in mice, leading to increased production of specific antibodies and cytokines.

Immunization with r-ScaF significantly reduced mortality and bacterial load in infected mice, suggesting its potential as a key component in developing a multivalent vaccine against Staphylococcus aureus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant Staphylococcal Antigen-F (r-ScaF), a novel vaccine candidate against methicillin resistant Staphylococcus aureus infection: Potency and efficacy studies. Majelan, PA., Mahdavi, M., Yazdi, MH., et al.[2019]

The investigational SA4Ag vaccine was found to be safe and well tolerated in a Phase 1 study involving 100 healthy adults, with no significant adverse events reported.

SA4Ag successfully induced high levels of bacteria-killing antibodies against Staphylococcus aureus, with significant increases in antibody titers observed by Day 29 post-vaccination, indicating strong immunogenicity and potential effectiveness in preventing infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SA4Ag, a 4-antigen Staphylococcus aureus vaccine, rapidly induces high levels of bacteria-killing antibodies. Begier, E., Seiden, DJ., Patton, M., et al.[2017]

A meta-analysis of three studies with 1,148 participants found that the SA4Ag and SA3Ag Staphylococcus aureus vaccines did not significantly increase systemic adverse events, indicating a good safety profile.

While there was a higher incidence of local adverse events associated with these vaccines, the rate of severe local adverse events was not significantly elevated, suggesting that the vaccines are generally well-tolerated in adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Staphylococcus aureus four-antigen and three-antigen vaccines in healthy adults: A meta-analysis of randomized controlled trials. Xu, X., Zhu, H., Lv, H.[2019]

The V710 vaccine did not significantly reduce the rate of serious postoperative Staphylococcus aureus infections in 8031 patients undergoing cardiothoracic surgery, showing similar efficacy to placebo.

Patients receiving the V710 vaccine experienced more adverse effects, including a higher rate of multiorgan failure and increased mortality among those who developed S. aureus infections, leading to the conclusion that the vaccine is not recommended for surgical patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of an investigational vaccine for preventing Staphylococcus aureus infections after cardiothoracic surgery: a randomized trial. Fowler, VG., Allen, KB., Moreira, ED., et al.[2022]

The Hib PRP-CRM197 vaccine was found to be well tolerated in a study of 764 Korean children aged 1-33 months, with 66% reporting mild adverse events, most of which were unrelated to the vaccine.

The safety profile of the Hib vaccine in this post-marketing surveillance study aligns with previous clinical studies, confirming its suitability for routine immunization against Hib disease in young children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SAFETY OF A CRM197-CONJUGATED HAEMOPHILUS INFLUENZAE TYPE B VACCINE IN KOREAN CHILDREN. Song, H., Bock, H., Guadagno, A., et al.[2018]

The investigational 4-antigen S. aureus vaccine (SA4Ag) was found to be safe and well tolerated in adults undergoing elective spinal fusion surgery, with mostly mild to moderate local and systemic reactions reported.

Despite generating strong immune responses, SA4Ag showed no efficacy in preventing postoperative S. aureus infections, as infection rates were identical in both the vaccine and placebo groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of a 4-Antigen Staphylococcus aureus Vaccine in Spinal Surgery: The STaphylococcus aureus suRgical Inpatient Vaccine Efficacy (STRIVE) Randomized Clinical Trial. Hassanzadeh, H., Baber, J., Begier, E., et al.[2023]

The study developed a novel nanoparticulate vaccine using a genetically engineered fusion protein (STa-LTB) that significantly reduces the enterotoxicity of STa, making it safer for use.

In mouse models, this nanovaccine induced stronger and longer-lasting antibody responses against enterotoxigenic Escherichia coli (ETEC) compared to traditional vaccine methods, suggesting it could be an effective option for preventing ETEC infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nanoparticulated heat-stable (STa) and heat-labile B subunit (LTB) recombinant toxin improves vaccine protection against enterotoxigenic Escherichia coli challenge in mouse. Deng, G., Zeng, J., Jian, M., et al.[2018]

Immunization of chickens with Salmonella enterica serovar Enteritidis ghosts carrying the LTB adjuvant resulted in significantly higher levels of plasma IgG and intestinal secretory IgA antibodies compared to those immunized with standard S. Enteritidis ghosts, indicating enhanced immune response.

The study demonstrated that S. Enteritidis-LTB ghosts not only improved antibody production but also reduced bacterial loads in the chickens' feces and internal organs, suggesting effective protection against salmonellosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salmonella enterica serovar enteritidis ghosts carrying the Escherichia coli heat-labile enterotoxin B subunit are capable of inducing enhanced protective immune responses. Jawale, CV., Lee, JH.[2021]

The STEBVax vaccine, which includes a modified staphylococcal enterotoxin B and an alum adjuvant, was found to be safe and well-tolerated in a first-in-human study involving 28 healthy adult volunteers, with no significant adverse events reported.

The vaccine induced a strong immune response, with approximately 93% of participants seroconverting to produce toxin-neutralizing antibodies after receiving doses between 2.5 and 20 μg, indicating its potential efficacy in preventing toxic shock from Staphylococcus aureus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Immunogenicity of a Parenterally Administered, Structure-Based Rationally Modified Recombinant Staphylococcal Enterotoxin B Protein Vaccine, STEBVax. Chen, WH., Pasetti, MF., Adhikari, RP., et al.[2022]

The study successfully transformed the centella plant with the synthetic ltb gene, resulting in the production of LTB protein, which is a strong immune adjuvant, in five out of seven transgenic plants.

The LTB protein was found to bind specifically to GM1-ganglioside, indicating that it formed active pentamers, which could enhance immune responses when used as an antigen in vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expression of Escherichia coli Heat-Labile Enterotoxin B Subunit in Centella (Centella asiatica (L.) Urban) via Biolistic Transformation. Loc, NH., Tung, NV., Kim, PTA., et al.[2021]

The study developed a fusion antigen (LT(192)-STb) that significantly enhanced the immunogenicity of the heat-stable toxin b (STb), which is crucial for creating effective vaccines against ETEC-associated diarrhea in pigs.

Immunized gilts produced piglets that remained healthy after exposure to an STb-positive ETEC strain, while most piglets from unimmunized gilts developed diarrhea, demonstrating the potential efficacy of the LT(192)-STb fusion in preventing porcine diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic fusions of heat-labile toxoid (LT) and heat-stable toxin b (STb) of porcine enterotoxigenic Escherichia coli elicit protective anti-LT and anti-STb antibodies. Zhang, W., Francis, DH.[2021]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

IBT-V02: A Multicomponent Toxoid Vaccine Protects Against Primary and Secondary Skin Infections Caused by Staphylococcus aureus. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and Immunogenicity of a 4-Component Toxoid-Based Staphylococcus aureus Vaccine in Rhesus Macaques. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Broad and Effective Protection against Staphylococcus aureus Is Elicited by a Multivalent Vaccine Formulated with Novel Antigens. [2020]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Rational Design of Toxoid Vaccine Candidates for Staphylococcus aureus Leukocidin AB (LukAB). [2021]

5. England pubmed.ncbi.nlm.nih.gov

Recombinant Staphylococcal Antigen-F (r-ScaF), a novel vaccine candidate against methicillin resistant Staphylococcus aureus infection: Potency and efficacy studies. [2019]

6. Netherlands pubmed.ncbi.nlm.nih.gov

SA4Ag, a 4-antigen Staphylococcus aureus vaccine, rapidly induces high levels of bacteria-killing antibodies. [2017]

7. United States pubmed.ncbi.nlm.nih.gov

Safety of Staphylococcus aureus four-antigen and three-antigen vaccines in healthy adults: A meta-analysis of randomized controlled trials. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Effect of an investigational vaccine for preventing Staphylococcus aureus infections after cardiothoracic surgery: a randomized trial. [2022]

9. Thailand pubmed.ncbi.nlm.nih.gov

SAFETY OF A CRM197-CONJUGATED HAEMOPHILUS INFLUENZAE TYPE B VACCINE IN KOREAN CHILDREN. [2018]

10. United States pubmed.ncbi.nlm.nih.gov

Efficacy of a 4-Antigen Staphylococcus aureus Vaccine in Spinal Surgery: The STaphylococcus aureus suRgical Inpatient Vaccine Efficacy (STRIVE) Randomized Clinical Trial. [2023]

11. Japan pubmed.ncbi.nlm.nih.gov

Nanoparticulated heat-stable (STa) and heat-labile B subunit (LTB) recombinant toxin improves vaccine protection against enterotoxigenic Escherichia coli challenge in mouse. [2018]

12. United States pubmed.ncbi.nlm.nih.gov

Salmonella enterica serovar enteritidis ghosts carrying the Escherichia coli heat-labile enterotoxin B subunit are capable of inducing enhanced protective immune responses. [2021]

13. United States pubmed.ncbi.nlm.nih.gov

Safety and Immunogenicity of a Parenterally Administered, Structure-Based Rationally Modified Recombinant Staphylococcal Enterotoxin B Protein Vaccine, STEBVax. [2022]

14. Netherlands pubmed.ncbi.nlm.nih.gov

Expression of Escherichia coli Heat-Labile Enterotoxin B Subunit in Centella (Centella asiatica (L.) Urban) via Biolistic Transformation. [2021]

15. United States pubmed.ncbi.nlm.nih.gov

Genetic fusions of heat-labile toxoid (LT) and heat-stable toxin b (STb) of porcine enterotoxigenic Escherichia coli elicit protective anti-LT and anti-STb antibodies. [2021]