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Safety and Immunogenicity of a Parenterally Administered, Structure-Based Rationally Modified Recombinant Staphylococcal Enterotoxin B Protein Vaccine, STEBVax
- Publication Year :
- 2016
- Publisher :
- American Society for Microbiology, 2016.
-
Abstract
- Staphylococcus aureus produces several enterotoxins and superantigens, exposure to which can elicit profound toxic shock. A recombinant staphylococcal enterotoxin B (rSEB) containing 3 distinct mutations in the major histocompatibility complex class II binding site was combined with an alum adjuvant (Alhydrogel) and used as a potential parenteral vaccine named STEBVax. Consenting healthy adult volunteers (age range, 23 to 38 years) participated in a first-in-human open-label dose escalation study of parenteral doses of STEBVax ranging from 0.01 μg up to 20 μg. Safety was assessed by determination of the frequency of adverse events and reactogenicity. Immune responses to the vaccination were determined by measurement of anti-staphylococcal enterotoxin B (anti-SEB) IgG by enzyme-linked immunosorbent assay and a toxin neutralization assay (TNA). Twenty-eight participants were enrolled in 7 dosing cohorts. All doses were well tolerated. The participants exhibited heterogeneous baseline antibody titers. More seroconversions and a faster onset of serum anti-SEB IgG toxin-neutralizing antibodies were observed by TNA with increasing doses of STEBVax. There was a trend for a plateau in antibody responses with doses of STEBVax of between 2.5 and 20 μg. Among the participants vaccinated with 2.5 μg to 20 μg of STEBVax, ∼93% seroconverted for SEB toxin-neutralizing antibody. A strong correlation between individual SEB-specific serum IgG antibody titers and the neutralization of gamma interferon production was found in vitro . STEBvax appeared to be safe and immunogenic, inducing functional toxin-neutralizing antibodies. These data support its continued clinical development. (This study has been registered at ClinicalTrials.gov under registration no. NCT00974935.)
- Subjects :
- 0301 basic medicine
Microbiology (medical)
Adult
Male
Staphylococcus aureus
Clinical Biochemistry
Immunology
Dose-Response Relationship, Immunologic
Enzyme-Linked Immunosorbent Assay
Enterotoxin
Immunoglobulin G
03 medical and health sciences
Enterotoxins
Interferon-gamma
Young Adult
Immunogenicity, Vaccine
Adjuvants, Immunologic
Immunology and Allergy
Medicine
Humans
Alum adjuvant
Vaccines
Reactogenicity
biology
business.industry
Immunogenicity
Antibody titer
Staphylococcal Vaccines
Virology
Antibodies, Bacterial
Antibodies, Neutralizing
Healthy Volunteers
Recombinant Proteins
Vaccination
030104 developmental biology
biology.protein
Female
Antibody
business
Subjects
Details
- Language :
- English
- ISSN :
- 00974935
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....ec490f0feb078d41b94fcb44983b8c81