A study in The Lancet eClinical Medicine in January 2024 presents the results of a Phase II study of a vaccine that could protect against toxic shock syndrome (TSS). Toxic shock syndrome toxin-1 (TSST-1) is a “superantigen” produced by Staphylococcus aureus that causes “life-threatening” TSS. The vaccine, a recombinant TSST-1 variant vaccine (rTTST-1v) was tested for safety, tolerability, and immunogenicity. The findings suggest that it was safe, well tolerated, and highly immunogenic.
An unmet medical need
Staphylococcus aureus-associated toxic shock syndrome was “first described as a menstruation-associated condition”, linked to the use of absorbent tampons. However, in a reported 50% of cases the “potentially lethal, rapidly progressing syndrome with rather unspecific initial symptoms” is of “non-menstrual origin”.
The authors describe how the superantigen characteristics of exotoxin TSST-1 drive it to bypass the conventional pathway of T-cell activation by “interfering directly” with the “class II major histocompatibility complex” on T-cells. This causes a subsequent release of interleukin (IL)-1, IL-6, TNF-α, TNF-β and IFN-γ and induces a cytokine storm. TSST-1 accounts for 85%-100% of menstrual toxic shock cases, in contrast to 40%-60% of nonmenstrual cases.
Although antibody titres against TSST-1 increase with age, an absence of neutralising antibodies, particularly in immunocompromised patients, children, and young adults, increases the risk of severe disease. Nonmenstrual toxic shock syndrome is often observed in conjunction with S. aureus-associated inefctions and is associated with a higher mortality than menstrual toxic shock syndrome.
“Consequently, the development of a safe and effective vaccine targeting TSST-1 remains an unmet medical need.”
rTTST-1v in trial
The rTSST-1v vaccine is a recombinant superantigen-based vaccine that contains a detoxified double-mutant rTSST-1 antigen. In a previous trial it was safe, well tolerated, and yielded a “strong” antibody response in a dose of up to 30 μg.
This Phase II trial allowed researchers to further assess these factors in increasing doses in healthy subjects through a prospective, single-centre, randomised, double-blind, parallel-group, adjuvant-controlled investigation of two doses of the vaccine. The trial lasted for 12-14 months, with an optional follow-up study for 27 months. Participants were between the ages of 18- and 64-years-old.
With similar numbers of adverse events observed across all groups, it is inferred that there is no dose dependency of adverse events. Indeed, safety results suggest that “single doses of 100 μg rTSST-1v may not be the maximum tolerated doses”, with potential to increase dosing for immunocompromised patients.
“It is our hypothesis that superantigenic exotoxins are crucial for the outcome of systemic disease. We aim to induce anti-toxic immunity with the toxic shock syndrome toxin-1 (TSST-1) as the main mTSS causative agent as target.”
Immunogenicity was demonstrated by the increase of TSST-1-binding and neutralising antibodies. Seroconversion rates were “consistently high”. A single dose of 100 μg rTSST-1v enhanced GMT>2-fold compared with the lower dose, and these higher GMT values persisted at 27 months. Despite a limited sample size, the researchers inferred that the 2 × 100 μg rTSST-1v yielded “numerically the best immune response after single and repeat injections”.
The low incidence of toxic shock syndrome “renders an efficacy trial unfeasible” like other toxoid vaccines. However, the authors think that efficacy of this vaccine could be assumed from serologic data of patients and controls.
“In summary the results of this trial represent a critical step towards a successful vaccine against S. aureus-associated toxic shock syndrome and support its continued development and testing in young adolescents.”
For more details read the paper here and let us know what you think of the study! If innovative vaccine development and research is your thing, why not join us at the Congress in Washington this April, or subscribe to our newsletters here?
