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


ABSTRACT: 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 3H-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 IFN?, TNF? 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.

SUBMITTER: Roetzer A 

PROVIDER: S-EPMC7601046 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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

Roetzer Andreas A   Stich Norbert N   Model Nina N   Schwameis Michael M   Firbas Christa C   Jilma Bernd B   Eibl Martha M MM  

Toxins 20201002 10


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 inhibi  ...[more]

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