High Titer Persistent Neutralizing Antibodies Induced by TSST-1 Variant Vaccine Against Toxic Shock Cytokine Storm

• Published in: Toxins Vol. 12; no. 10; p. 640
• Main Authors: Roetzer, Andreas, Stich, Norbert, Model, Nina, Schwameis, Michael, Firbas, Christa, Jilma, Bernd, Eibl, Martha M
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 02.10.2020; MDPI
• Subjects: Antibodies; Cell activation; Cell growth; Clinical trials; Cytokine storm; Cytokines; Dilution; Endocarditis; Gene expression; Immune response; Immune system; Immunization; Immunogenicity; Immunology; Inflammation; Interleukin 2; Interleukin 6; Lymphocytes; Lymphocytes T; Menstruation; Neutralization; Neutralizing; neutralizing antibodies; Placebos; Sepsis; Septic shock; Staphylococcal enterotoxin F; Staphylococcus; Subgroups; Thymidine; Toxic shock syndrome; Toxins; Tumor necrosis factor-α; Vaccination; Vaccines; γ-Interferon; neutralizing antibodies; toxic shock syndrome; Staphylococcus; immunogenicity
• ISSN: 2072-6651; 2072-6651
• DOI: 10.3390/toxins12100640

Staphylococcal superantigen toxins lead to a devastating cytokine storm resulting in shock and multi-organ failure. We have previously assessed the safety and immunogenicity of a recombinant toxic shock syndrome toxin 1 variant vaccine (rTSST-1v) in clinical trials (NCT02971670 and NCT02340338). The current study assessed neutralizing antibody titers after repeated vaccination with escalating doses of rTSST-1v. At study entry, 23 out of 34 subjects (67.6%) had neutralizing antibody titers inhibiting T cell activation as determined by H-thymidine incorporation at a serum dilution of ≤1:100 with similar figures for inhibition of IL-2 activation (19 of 34 subjects, 55.9%) as assessed by quantitative PCR. After the first vaccination, numbers of subjects with neutralization titers inhibiting T cell activation (61.7% ≥ 1:1000) and inhibiting IL-2 gene induction (88.2% ≥ 1:1000) increased. The immune response was augmented after the second vaccination (inhibiting T cell activation: 78.8% ≥ 1:1000; inhibiting IL-2 induction: 93.9% ≥ 1:1000) corroborated with a third immunization months later in a small subgroup of subjects. Assessment of IFNγ, TNFα and IL-6 inhibition revealed similar results, whereas neutralization titers did not change in placebo participants. Antibody titer studies show that vaccination with rTSST-1v in subjects with no/low neutralizing antibodies can rapidly induce high titer neutralizing antibodies persisting over months.