Breakthrough data for first vaccine against Staphylococcal-induced Toxic Shock Syndrome (TSS) published in eClinicalMedicine, part of The Lancet Discovery Science

• Phase 2 studies showed the TSS1-T vaccine to be safe and effective, offering potential preventative therapy for vulnerable groups and medical workers
• Staphylococcal-induced TSS is a serious and life-threatening condition affecting patients with compromised immunity and premenopausal women
• Results encouraging for the development of a toxoid-based, multi-component vaccine against sensitive and resistant Staphylococcus aureus infections, a significant threat to patients and financial burden for healthcare systems

Vienna, Austria, 9 January 2024 – The first vaccine to potentially prevent staphylococcal-induced toxic shock syndrome (TSS) has successfully completed a phase 2 study, with the data published in the journal eClinicalMedicine, part of the Lancet Discovery Science (1). TSS is a life-threatening condition caused by bacterial toxins, which can lead to multiple organ failure and death. The same antigens used against TSS will also form part of a multicomponent vaccine against staphylococcal infections.

Researchers from Biomedical Research & Bio-Products AG under the direction of Prof. Dr. Martha Eibl conducted the clinical phase 2 study in collaboration with the University Clinic for Clinical Pharmacology at MedUni Vienna, Austria. The promising results show that the TSST-1 vaccine is safe and effective, with immunization lasting for at least two years.

“Toxic shock syndrome is a serious condition and there are estimations that it can be fatal in almost 10% of cases (2). TSS affects people with weakened immune systems due to chronic illness, surgery or dialysis treatments. It is also associated with tampon use in young women,” said Dr. Andreas Roetzer, Head of R&D for Vaccines at Biomedical Research & Bio-Products. “With the very encouraging data from the phase 2 trial, building on a successful phase 1, we believe the TSST-1 vaccine represents a real breakthrough in protecting these vulnerable groups, as well as healthcare workers in high-risk situations. In addition to promising results against TSS, the successful development of a detoxified toxin antigen is also a first step towards developing a general staphylococcal vaccine based on toxins and other secreted antigens. We are pleased to publish the full phase 2 data and look forward taking the next steps to develop a multi-component vaccine.”

“The vaccine (3) developed from a detoxified staphylococcal toxin is administered intramuscularly and has a similar effect to a tetanus vaccination,” explained Prof. Dr. Bernd Jilma from the University Clinic for Clinical Pharmacology at MedUni Vienna. “After vaccination with TSST-1, individuals develop antibodies that offer protection. Of the 126 subjects that completed the study, more than 80% developed protection after the first vaccination. More than 85% still had protection 18 months after the third vaccination with the higher dose. The vaccination is effective irrespective of whether or not strains are resistant to antibiotics. A simple blood test can be used to determine whether someone has low antibody levels, so that people at risk can be vaccinated preventatively.”

Staphylococci pose a substantial health risk

Most people are affected by antibiotic-sensitive or resistant staphylococci colonization, especially on the skin and mucosa, but the presence of the bacteria is generally harmless and goes unnoticed. However, staphylococcus can cause serious illness in people whose immune system is compromised or who have to undergo major surgery. This includes toxic shock syndrome, which is unique and can affect previously healthy young people as well as those who are already ill. Delayed elimination of resistant staphylococci (MRSA) can encourage this outcome. Infections with MRSA are more difficult to treat and therapies are more expensive as the length of hospital stays is significantly prolonged. If treatment does not result in rapid clearance of the bacterial pathogen, potentially life-threatening conditions such as septic or toxic shock may occur.

Menstrual TSS accounts for around 50% of cases

TSS is also associated with tampon use in young women, which accounts for around 50% of all cases. The syndrome was first described in the 1980s, with general symptoms of sepsis or blood poisoning in young girls who had used so-called ‘super tampons’. This led to regulation of the absorption capacity of tampons. According to a recent study in France, the condition still has an incidence of 1/100,000 (4). According to the Robert-Koch-Institute, the incidence in Germany in 2015 was 3 to 6 cases per 100,000 women of sexually active age (5). Hospitalization at intensive care units, immediate shock management, and administration of antibiotics comprise the necessary treatment.

Multicomponent vaccine to combat staphylococcal infections

Several attempts to develop a vaccine against staphylococci using classic polysaccharide antigens have already failed in clinical trials (6). Researchers at Biomedical Research & Bio-Products have identified a specific class of toxins that are not only associated with TSS, but could also play an important role in other diseases caused by staphylococci.

Detoxified variants of the medically relevant toxins are now to be combined into a multi-component vaccine at Biomedical Research & Bio-Products. In addition to toxins, other antigens secreted by staphylococci will also be included, which can attack an important part of the human immune system, the complement system. For a successful vaccine strategy, the researchers are also focusing on surface proteins as antigens so that phagocytes of the human immune system can be activated more effectively. The first preclinical studies with variants of the multicomponent vaccine have already been successfully carried out, and more are being planned.

“We see in our preclinical data that a multicomponent vaccine based on toxins and other antigens released into the host environment would have a good chance of successfully counteracting staphylococcal infections. We are currently in discussions with partners and investors to be able to implement our strategy for a vaccine against staphylococci,” added Dr. Roetzer.

References

(1)     A Randomized, Double-Blind Study on the Safety and Immunogenicity of rTSST-1 Variant Vaccine: Phase 2 Results. EClinicalMedicine. Christian Schoergenhofer, Georg Gelbenegger, Dzenita Hasanacevic, Léa Schöner, Margarete M. Steiner, Christa Firbas, Nina Buchtele, Ulla Derhaschnig, Andreas Tanzmann, Nina Model, Julian Larcher-Senn, Manuel Drost, Martha M. Eibl, Andreas Roetzer* and Bernd Jilma*.

https://www.sciencedirect.com/science/article/pii/S2589537023005813

(2)     Toxic Shock Syndrome (book, published by StatPearls Publishing LLC. Adam Ross and Hugh W. Shoff. PMID: 29083727; https://www.ncbi.nlm.nih.gov/books/NBK459345/

(3)     Safety, tolerability, and immunogenicity of a recombinant toxic shock syndrome toxin (rTSST)-1 variant vaccine: a randomised, double-blind, adjuvant-controlled, dose escalation first-in-man-trial. Lancet Infectious Diseases, June 2016. M. Schwameis, B. Roppenser, C. Firbas, C. Gruener, N. Model, N. Stich, A. Roetzer, N. Buchtele, B. Jilma, M. Eibl. https://doi.org/10.1016/S1473-3099(16)30115-3

(4)     Association of Characteristics of Tampon Use With Menstrual Toxic Shock Syndrome in France, EClinicalMedicine. A Billion, M-P Gustin, A Tristan, T Benet, J Berthiller, CA Gustave, P Vanhems, G.

https://doi.org/10.1016/j.eclinm.2020.100308

(5)     Staphylokokken-Erkrankungen, insbesondere Infektionen durch MRSA. RKI-Ratgeber, Robert Koch-Institut. Link to read article

(6)     Vaccines for healthcare associated infections without vaccine prevention to date. Vaccine, eCollection
2022 Aug. A. Gagneux-Brunon, J. Gagnaire, C. Pelissier, B. Philippe, E. Botelho-Nevers. https://doi.org/10.1016/j.jvacx.2022.100168

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About Biomedical Research & Bio-Products AG

Biomedical Research & Bio-Products AG is a biopharmaceutical company based in Vienna, Austria, which is engaged in R&D, manufacturing and preclinical and clinical testing of potential vaccine candidates against infections caused by Staphylococcus aureus.

The company was founded in 2019 through the merger of Biomedizinische Forschungs-gesellschaft mbH and Bio-Products & Bio-Engineering AG.

For more information, please visit: https://bio.co.at/