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 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.
Keywords:
Staphylococcus; immunogenicity; neutralizing antibodies; toxic shock syndrome.
Publication types
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Observational Study
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Randomized Controlled Trial
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Research Support, Non-U.S. Gov't
MeSH terms
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Antibodies, Bacterial / blood*
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Antibodies, Neutralizing / blood*
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Bacterial Toxins / administration & dosage*
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Bacterial Toxins / genetics
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Bacterial Toxins / immunology
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Cells, Cultured
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Cytokine Release Syndrome / immunology
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Cytokine Release Syndrome / microbiology
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Cytokine Release Syndrome / prevention & control*
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Cytokines / genetics
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Cytokines / metabolism
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Double-Blind Method
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Enterotoxins / administration & dosage*
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Enterotoxins / genetics
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Enterotoxins / immunology
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Humans
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Immunogenicity, Vaccine*
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Lymphocyte Activation / drug effects
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Prospective Studies
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Shock, Septic / immunology
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Shock, Septic / microbiology
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Shock, Septic / prevention & control*
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Single-Blind Method
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Staphylococcal Infections / immunology
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Staphylococcal Infections / microbiology
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Staphylococcal Infections / prevention & control*
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Staphylococcal Vaccines / administration & dosage*
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Staphylococcal Vaccines / genetics
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Staphylococcal Vaccines / immunology
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Staphylococcus aureus / drug effects*
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Staphylococcus aureus / immunology
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Staphylococcus aureus / pathogenicity
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Superantigens / administration & dosage*
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Superantigens / genetics
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Superantigens / immunology
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism
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Time Factors
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Treatment Outcome
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Vaccination
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Vaccines, Synthetic / administration & dosage
Substances
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Antibodies, Bacterial
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Antibodies, Neutralizing
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Bacterial Toxins
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Cytokines
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Enterotoxins
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Staphylococcal Vaccines
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Superantigens
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Vaccines, Synthetic
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enterotoxin F, Staphylococcal