title: Safety and immunogenicity of a recombinant Staphylococcus aureus α-toxoid and a recombinant Panton-Valentine leukocidin subunit, in healthy adults.
abstract: We conducted a randomized, double-blind, placebo-controlled dose-escalation study in healthy adults to evaluate the safety and immunogenicity of recombinant Staphylococcus aureus candidate vaccine antigens, recombinant α-toxoid (rAT) and a sub-unit of Panton-Valentine leukocidin (rLukS-PV). 176 subjects were enrolled and randomized within 1 of 11 treatment cohorts: monovalent rAT or rLukS-PV dosages of 10, 25, 50, and 100 μg; bivalent rAT:rLukS dosages of 10:10, 25:25, and 50:50 μg; and alum or saline placebo. All subjects were assessed at Days 0, 7, 14, 28, and 84. Subjects in the 50:50 μg bivalent cohort received a second injection on Day 84 and were assessed on Days 98 and 112. Incidence and severity of reactogenicity and adverse events (AEs) were compared. Geometric mean serum concentrations (GMC) and neutralizing activity of anti-rAT and anti-rLukS-PV IgG were assessed. Reactogenicity incidence was significantly higher in vaccine than placebo recipients (77% versus 55%, respectively; p = 0.006). However, 77% of reactogenicity events were mild and 19% were moderate in severity. The AE incidence and severity were similar between the cohorts. All monovalent and bivalent rAT dosages resulted in a significant increase in the anti-rAT IgG and anti- rLukS-PV GMCs between day 0 and 28 compared with placebo, and persisted through Day 84. Exploratory subgroup analyses suggested a higher GMC and neutralizing antibody titers for the 50 μg monovalent or bivalent rAT and rLukS-PV dose as compared to the other doses. No booster effect was observed after administration of the second dose. We conclude that the rAT and rLukS-PV vaccine formulations were well-tolerated and had a favorable immunogenicity profile, producing antibody with neutralizing activity through day 84. There was no benefit observed with a booster dose of the vaccine.
authors.affiliation: a Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics , Uniformed Services University of the Health Sciences , Rockville , MD , USA.|b Division of Infectious Diseases , San Antonio Military Medical Center , Fort Sam Houston , TX , USA.|c Henry M. Jackson Foundation for the Advancement of Military Medicine , Bethesda , MD , USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Landrum
authors.affiliation: a Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics , Uniformed Services University of the Health Sciences , Rockville , MD , USA.|c Henry M. Jackson Foundation for the Advancement of Military Medicine , Bethesda , MD , USA.|d Division of Infectious Diseases , Naval Medical Center Portsmouth , Portsmouth , VA , USA.
authors.forename: Tahaniyat
authors.initials: T
authors.lastname: Lalani
authors.affiliation: e Nabi Biopharmaceuticals , Rockville , MD , USA.
authors.forename: Minoo
authors.initials: M
authors.lastname: Niknian
authors.affiliation: d Division of Infectious Diseases , Naval Medical Center Portsmouth , Portsmouth , VA , USA.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Maguire
authors.affiliation: b Division of Infectious Diseases , San Antonio Military Medical Center , Fort Sam Houston , TX , USA.
authors.forename: Duane R
authors.initials: DR
authors.lastname: Hospenthal
authors.affiliation: e Nabi Biopharmaceuticals , Rockville , MD , USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Fattom
authors.affiliation: e Nabi Biopharmaceuticals , Rockville , MD , USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Taylor
authors.affiliation: a Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics , Uniformed Services University of the Health Sciences , Rockville , MD , USA.|c Henry M. Jackson Foundation for the Advancement of Military Medicine , Bethesda , MD , USA.
authors.forename: Jamie
authors.initials: J
authors.lastname: Fraser
authors.affiliation: a Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics , Uniformed Services University of the Health Sciences , Rockville , MD , USA.|c Henry M. Jackson Foundation for the Advancement of Military Medicine , Bethesda , MD , USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Wilkins
authors.affiliation: f Infectious Diseases Division , University of Toledo College of Medicine and Life Sciences , Toledo , OH , USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Ellis
authors.affiliation: e Nabi Biopharmaceuticals , Rockville , MD , USA.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Kessler
authors.affiliation: e Nabi Biopharmaceuticals , Rockville , MD , USA.
authors.forename: Rafaat E F
authors.initials: RE
authors.lastname: Fahim
authors.affiliation: a Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics , Uniformed Services University of the Health Sciences , Rockville , MD , USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Tribble
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000293:Adolescent; D000328:Adult; D000534:Alum Compounds / Q000008:administration & dosage; D000907:Antibodies, Bacterial / Q000097:blood; D057134:Antibodies, Neutralizing / Q000097:blood; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology*; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005098:Exotoxins / Q000235:genetics / Q000276:immunology*; D005260:Female; D064368:Healthy Volunteers; D006460:Hemolysin Proteins / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007956:Leukocidins / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D013203:Staphylococcal Infections / Q000517:prevention & control*; D013209:Staphylococcal Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000235:genetics / Q000276:immunology*; D014121:Toxoids / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000907:Antibodies, Bacterial; D057134:Antibodies, Neutralizing; D001427:Bacterial Toxins; D005098:Exotoxins; D006460:Hemolysin Proteins; D007074:Immunoglobulin G; D007956:Leukocidins; C078284:Panton-Valentine leukocidin; D010919:Placebos; D013209:Staphylococcal Vaccines; D014121:Toxoids; D014614:Vaccines, Synthetic; C021091:staphylococcal alpha-toxin; C041524:aluminum sulfate
keywords: Staphylococcus aureus; bacterial vaccine; recombinant Panton-Valentine leukocidin; recombinant α-toxoid