PMID- 25715157
OWN - NLM
STAT- MEDLINE
DCOM- 20151222
LR  - 20240323
IS  - 2164-554X (Electronic)
IS  - 2164-5515 (Print)
IS  - 2164-5515 (Linking)
VI  - 11
IP  - 3
DP  - 2015
TI  - Safety and immunogenicity of an investigational 4-component Staphylococcus aureus 
      vaccine with or without AS03B adjuvant: Results of a randomized phase I trial.
PG  - 620-31
LID - 10.1080/21645515.2015.1011021 [doi]
AB  - We assessed the safety, reactogenicity and immunogenicity of a staphylococcal 
      vaccine combining capsular polysaccharides types 5 and 8 (CPS5/8), conjugated to 
      tetanus toxoid (TT), with mutated detoxified alpha-toxin (AT) and clumping factor A 
      (ClfA). In this phase I, randomized, placebo-controlled, observer-blind trial 
      (NCT01160172), 88 healthy 18- to 40-year-olds received CPS5-TT/CPS8-TT/AT/ClfA 
      vaccine (5/5/10/10 mug or 10/10/30/30 mug dose, each with or without AS03B 
      adjuvant) or saline, at months 0, 1, 6. Solicited and unsolicited adverse events 
      (AEs) were recorded for 7 and 30 d post-vaccination, respectively; potential 
      immune-mediated diseases (pIMDs) and serious AEs (SAEs) were recorded throughout 
      the study. Humoral and antigen-specific CD4(+)/CD8(+) T-cell immunity were 
      assessed from Day (D) 0 to D540 post-vaccination. The most frequently reported 
      solicited local and general AEs were pain (78.6%-100% of subjects), fatigue 
      (36.4%-93.3% of subjects post-dose 1-2) and headache (20%-44.4% of subjects 
      post-dose 3). Overall, 4 SAEs and 2 potential immune-mediated diseases (pIMDs) 
      (none fatal or vaccine-related) were reported. For each antigen, pre-vaccination 
      seropositivity rates were high (85.7%-100%) and geometric mean concentrations 
      (GMCs) in vaccine recipients sharply increased from D0 to D14, then plateaued to 
      study end. Exploratory group comparisons suggested higher GMCs with higher 
      dosage, without AS03B effect. Vaccine-induced antibodies were functional (CPS5 
      opsonophagocytic assays, and AT/ClfA inhibition assays). AT- and ClfA-specific 
      CD4(+) T-cells with Th0/Th1 cytokine profile were induced at low levels (median 
      <0.05%) by each formulation (intracellular cytokine staining). In conclusion, no 
      safety concerns were identified and each vaccine formulation induced robust 
      humoral immune responses after the first vaccine dose.
FAU - Levy, Jack
AU  - Levy J
AD  - a Saint-Pierre University Hospital ; Brussels , Belgium.
FAU - Licini, Laurent
AU  - Licini L
FAU - Haelterman, Edwige
AU  - Haelterman E
FAU - Moris, Philippe
AU  - Moris P
FAU - Lestrate, Pascal
AU  - Lestrate P
FAU - Damaso, Silvia
AU  - Damaso S
FAU - Van Belle, Pascale
AU  - Van Belle P
FAU - Boutriau, Dominique
AU  - Boutriau D
LA  - eng
SI  - ClinicalTrials.gov/NCT01160172
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hum Vaccin Immunother
JT  - Human vaccines & immunotherapeutics
JID - 101572652
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Antibodies, Bacterial)
RN  - 0 (Drug Combinations)
RN  - 0 (Placebos)
RN  - 0 (Polysorbates)
RN  - 0 (Staphylococcal Vaccines)
RN  - 7QWM220FJH (Squalene)
RN  - A7YT618XBV (AS03 adjuvant)
RN  - H4N855PNZ1 (alpha-Tocopherol)
SB  - IM
MH  - Adjuvants, Immunologic/administration & dosage
MH  - Adolescent
MH  - Adult
MH  - Antibodies, Bacterial/blood
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Drug Combinations
MH  - Drug-Related Side Effects and Adverse Reactions/epidemiology/pathology
MH  - Female
MH  - Healthy Volunteers
MH  - Humans
MH  - Male
MH  - Placebos/administration & dosage
MH  - Polysorbates/administration & dosage
MH  - Single-Blind Method
MH  - Squalene/administration & dosage
MH  - Staphylococcal Infections/immunology/*prevention & control
MH  - Staphylococcal Vaccines/*adverse effects/*immunology
MH  - Young Adult
MH  - alpha-Tocopherol/administration & dosage
PMC - PMC4514337
OTO - NOTNLM
OT  - AEs
OT  - According-to-Protocol; CIs
OT  - Confidence Intervals; ClfA
OT  - Panton-Valentine leucocidin; rEPA
OT  - Staphylococcus aureus
OT  - adjuvant
OT  - adverse events; AT
OT  - capsular polysaccharides types 5 and 8; GMC
OT  - clumping factor A; CPS5 and 8
OT  - geometric mean concentration; GMT
OT  - geometric mean titer; ICS
OT  - immunogenicity
OT  - interferon; IL
OT  - interleukin; LNR
OT  - intracellular cytokine staining; IFN
OT  - laboratory normal range; MRSA
OT  - methicillin-resistant S. aureus; OPA
OT  - opsonophagocytic assay; pIMDs
OT  - potential immune-mediated diseases: PVL
OT  - recombinant exoprotein A from Pseudomonas aeruginosa; SAEs
OT  - safety
OT  - serious adverse events; TT
OT  - tetanus toxoid
OT  - vaccine
OT  - alpha-toxin; ATP
EDAT- 2015/02/26 06:00
MHDA- 2015/12/23 06:00
PMCR- 2016/02/03
CRDT- 2015/02/26 06:00
PHST- 2015/02/26 06:00 [entrez]
PHST- 2015/02/26 06:00 [pubmed]
PHST- 2015/12/23 06:00 [medline]
PHST- 2016/02/03 00:00 [pmc-release]
AID - 1011021 [pii]
AID - 10.1080/21645515.2015.1011021 [doi]
PST - ppublish
SO  - Hum Vaccin Immunother. 2015;11(3):620-31. doi: 10.1080/21645515.2015.1011021.