PMID- 28010246 OWN - NLM STAT- MEDLINE DCOM- 20170424 LR - 20181113 IS - 2164-554X (Electronic) IS - 2164-5515 (Print) IS - 2164-5515 (Linking) VI - 13 IP - 4 DP - 2017 Apr 3 TI - Safety and immunogenicity of a recombinant Staphylococcus aureus alpha-toxoid and a recombinant Panton-Valentine leukocidin subunit, in healthy adults. PG - 791-801 LID - 10.1080/21645515.2016.1248326 [doi] AB - 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 alpha-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 mug; bivalent rAT:rLukS dosages of 10:10, 25:25, and 50:50 mug; and alum or saline placebo. All subjects were assessed at Days 0, 7, 14, 28, and 84. Subjects in the 50:50 mug 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 mug 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. FAU - Landrum, Michael L AU - Landrum ML AD - a Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics , Uniformed Services University of the Health Sciences , Rockville , MD , USA. AD - b Division of Infectious Diseases , San Antonio Military Medical Center , Fort Sam Houston , TX , USA. AD - c Henry M. Jackson Foundation for the Advancement of Military Medicine , Bethesda , MD , USA. FAU - Lalani, Tahaniyat AU - Lalani T AD - a Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics , Uniformed Services University of the Health Sciences , Rockville , MD , USA. AD - c Henry M. Jackson Foundation for the Advancement of Military Medicine , Bethesda , MD , USA. AD - d Division of Infectious Diseases , Naval Medical Center Portsmouth , Portsmouth , VA , USA. FAU - Niknian, Minoo AU - Niknian M AD - e Nabi Biopharmaceuticals , Rockville , MD , USA. FAU - Maguire, Jason D AU - Maguire JD AD - d Division of Infectious Diseases , Naval Medical Center Portsmouth , Portsmouth , VA , USA. FAU - Hospenthal, Duane R AU - Hospenthal DR AD - b Division of Infectious Diseases , San Antonio Military Medical Center , Fort Sam Houston , TX , USA. FAU - Fattom, Ali AU - Fattom A AD - e Nabi Biopharmaceuticals , Rockville , MD , USA. FAU - Taylor, Kimberly AU - Taylor K AD - e Nabi Biopharmaceuticals , Rockville , MD , USA. FAU - Fraser, Jamie AU - Fraser J AD - a Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics , Uniformed Services University of the Health Sciences , Rockville , MD , USA. AD - c Henry M. Jackson Foundation for the Advancement of Military Medicine , Bethesda , MD , USA. FAU - Wilkins, Kenneth AU - Wilkins K AD - a Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics , Uniformed Services University of the Health Sciences , Rockville , MD , USA. AD - c Henry M. Jackson Foundation for the Advancement of Military Medicine , Bethesda , MD , USA. FAU - Ellis, Michael W AU - Ellis MW AD - f Infectious Diseases Division , University of Toledo College of Medicine and Life Sciences , Toledo , OH , USA. FAU - Kessler, Paul D AU - Kessler PD AD - e Nabi Biopharmaceuticals , Rockville , MD , USA. FAU - Fahim, Rafaat E F AU - Fahim RE AD - e Nabi Biopharmaceuticals , Rockville , MD , USA. FAU - Tribble, David R AU - Tribble DR AD - a Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics , Uniformed Services University of the Health Sciences , Rockville , MD , USA. LA - eng GR - Y01 AI005072/AI/NIAID NIH HHS/United States PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20161223 PL - United States TA - Hum Vaccin Immunother JT - Human vaccines & immunotherapeutics JID - 101572652 RN - 0 (Adjuvants, Immunologic) RN - 0 (Alum Compounds) RN - 0 (Antibodies, Bacterial) RN - 0 (Antibodies, Neutralizing) RN - 0 (Bacterial Toxins) RN - 0 (Exotoxins) RN - 0 (Hemolysin Proteins) RN - 0 (Immunoglobulin G) RN - 0 (Leukocidins) RN - 0 (Panton-Valentine leukocidin) RN - 0 (Placebos) RN - 0 (Staphylococcal Vaccines) RN - 0 (Toxoids) RN - 0 (Vaccines, Synthetic) RN - 0 (staphylococcal alpha-toxin) RN - 34S289N54E (aluminum sulfate) SB - IM MH - Adjuvants, Immunologic/administration & dosage MH - Adolescent MH - Adult MH - Alum Compounds/administration & dosage MH - Antibodies, Bacterial/blood MH - Antibodies, Neutralizing/blood MH - Bacterial Toxins/genetics/*immunology MH - Double-Blind Method MH - Drug-Related Side Effects and Adverse Reactions/epidemiology/pathology MH - Exotoxins/genetics/*immunology MH - Female MH - Healthy Volunteers MH - Hemolysin Proteins/genetics/*immunology MH - Humans MH - Immunoglobulin G/blood MH - Leukocidins/genetics/*immunology MH - Male MH - Middle Aged MH - Placebos/administration & dosage MH - Staphylococcal Infections/*prevention & control MH - Staphylococcal Vaccines/administration & dosage/*adverse effects/genetics/*immunology MH - Toxoids/genetics/*immunology MH - Vaccines, Synthetic/administration & dosage/adverse effects/genetics/immunology MH - Young Adult PMC - PMC5404372 OTO - NOTNLM OT - Staphylococcus aureus OT - bacterial vaccine OT - recombinant Panton-Valentine leukocidin OT - recombinant alpha-toxoid EDAT- 2016/12/25 06:00 MHDA- 2017/04/25 06:00 PMCR- 2017/12/23 CRDT- 2016/12/25 06:00 PHST- 2016/12/25 06:00 [pubmed] PHST- 2017/04/25 06:00 [medline] PHST- 2016/12/25 06:00 [entrez] PHST- 2017/12/23 00:00 [pmc-release] AID - 1248326 [pii] AID - 10.1080/21645515.2016.1248326 [doi] PST - ppublish SO - Hum Vaccin Immunother. 2017 Apr 3;13(4):791-801. doi: 10.1080/21645515.2016.1248326. Epub 2016 Dec 23.