PMID- 29172945
OWN - NLM
STAT- MEDLINE
DCOM- 20190111
LR  - 20190111
IS  - 2164-554X (Electronic)
IS  - 2164-5515 (Print)
IS  - 2164-5515 (Linking)
VI  - 14
IP  - 1
DP  - 2018 Jan 2
TI  - A phase I, randomized, controlled, dose-ranging study of investigational 
      acellular pertussis (aP) and reduced tetanus-diphtheria-acellular pertussis 
      (TdaP) booster vaccines in adults.
PG  - 45-58
LID - 10.1080/21645515.2017.1385686 [doi]
AB  - Despite high vaccination coverage worldwide, pertussis has re-emerged in many 
      countries. This randomized, controlled, observer-blind phase I study and 
      extension study in Belgium (March 2012-June 2015) assessed safety and 
      immunogenicity of investigational acellular pertussis vaccines containing 
      genetically detoxified pertussis toxin (PT) (NCT01529645; NCT02382913). 420 
      healthy adults (average age: 26.8 +/- 5.5 years, 60% female) were randomized to 1 
      of 10 vaccine groups: 3 investigational aP vaccines (containing pertussis 
      antigens PT, filamentous hemagglutinin [FHA] and pertactin [PRN] at different 
      dosages), 6 investigational TdaP (additionally containing tetanus toxoid [TT] and 
      diphtheria toxoid [DT]), and 1 TdaP comparator containing chemically inactivated 
      PT. Antibody responses were evaluated on days 1, 8, 30, 180, 365, and 
      approximately 3 years post-booster vaccination. Cell-mediated immune responses 
      and PT neutralization were evaluated in a subset of participants in pre-selected 
      groups. Local and systemic adverse events (AEs), and unsolicited AEs were 
      collected through day 7 and 30, respectively; serious AEs and AEs leading to 
      study withdrawal were collected through day 365 post-vaccination. Antibody 
      responses against pertussis antigens peaked at day 30 post-vaccination and then 
      declined but remained above baseline level at approximately 3 years 
      post-vaccination. Responses to FHA and PRN were correlated to antigen dose. 
      Antibody responses specific to PT, toxin neutralization activity and persistence 
      induced by investigational formulations were similar or significantly higher than 
      the licensed vaccine, despite lower PT doses. Of 15 serious AEs, none were 
      considered vaccination-related; 1 led to study withdrawal (premature labor, day 
      364; aP4 group). This study confirmed the potential benefits of genetically 
      detoxified PT antigen. All investigational study formulations were well 
      tolerated.
FAU - Leroux-Roels, Geert
AU  - Leroux-Roels G
AD  - a Centre for Vaccinology, Ghent University and University Hospital , Ghent , 
      Belgium.
FAU - Lattanzi, Maria
AU  - Lattanzi M
AD  - b GSK, Vaccines , Siena , Italy.
FAU - Solis, Claudia Dovali
AU  - Solis CD
AD  - b GSK, Vaccines , Siena , Italy.
FAU - Contorni, Mario
AU  - Contorni M
AD  - b GSK, Vaccines , Siena , Italy.
FAU - Costantini, Marco
AU  - Costantini M
AD  - b GSK, Vaccines , Siena , Italy.
FAU - Moraschini, Luca
AU  - Moraschini L
AD  - b GSK, Vaccines , Siena , Italy.
FAU - Bardelli, Monia
AU  - Bardelli M
AD  - b GSK, Vaccines , Siena , Italy.
FAU - Bertholet, Sylvie
AU  - Bertholet S
AD  - b GSK, Vaccines , Siena , Italy.
FAU - Borgogni, Erica
AU  - Borgogni E
AD  - b GSK, Vaccines , Siena , Italy.
FAU - Buricchi, Francesca
AU  - Buricchi F
AD  - b GSK, Vaccines , Siena , Italy.
FAU - Cantisani, Rocco
AU  - Cantisani R
AD  - b GSK, Vaccines , Siena , Italy.
FAU - Faenzi, Elisa
AU  - Faenzi E
AD  - b GSK, Vaccines , Siena , Italy.
FAU - Finco, Oretta
AU  - Finco O
AD  - b GSK, Vaccines , Siena , Italy.
FAU - Leuzzi, Rosanna
AU  - Leuzzi R
AD  - b GSK, Vaccines , Siena , Italy.
FAU - Pizza, Mariagrazia
AU  - Pizza M
AD  - b GSK, Vaccines , Siena , Italy.
FAU - Rosa, Domenico
AU  - Rosa D
AD  - b GSK, Vaccines , Siena , Italy.
FAU - Schiavetti, Francesca
AU  - Schiavetti F
AD  - b GSK, Vaccines , Siena , Italy.
FAU - Seubert, Anja
AU  - Seubert A
AD  - b GSK, Vaccines , Siena , Italy.
FAU - Spensieri, Fabiana
AU  - Spensieri F
AD  - b GSK, Vaccines , Siena , Italy.
FAU - Volpini, Gianfranco
AU  - Volpini G
AD  - b GSK, Vaccines , Siena , Italy.
FAU - Zedda, Luisanna
AU  - Zedda L
AD  - b GSK, Vaccines , Siena , Italy.
FAU - Giudice, Giuseppe Del
AU  - Giudice GD
AD  - b GSK, Vaccines , Siena , Italy.
FAU - Galgani, Ilaria
AU  - Galgani I
AD  - b GSK, Vaccines , Siena , Italy.
LA  - eng
SI  - ClinicalTrials.gov/NCT01529645
SI  - ClinicalTrials.gov/NCT02382913
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20171127
PL  - United States
TA  - Hum Vaccin Immunother
JT  - Human vaccines & immunotherapeutics
JID - 101572652
RN  - 0 (Antibodies, Bacterial)
RN  - 0 (Diphtheria-Tetanus-acellular Pertussis Vaccines)
RN  - 0 (Pertussis Vaccine)
RN  - EC 2.4.2.31 (Pertussis Toxin)
SB  - IM
MH  - Adult
MH  - Antibodies, Bacterial/analysis
MH  - Belgium
MH  - Diphtheria-Tetanus-acellular Pertussis Vaccines/*administration & dosage/adverse 
      effects/genetics/immunology
MH  - Female
MH  - Humans
MH  - Immunity, Cellular
MH  - Immunization, Secondary/*methods
MH  - Immunogenicity, Vaccine
MH  - Male
MH  - Pertussis Toxin/genetics/*immunology
MH  - Pertussis Vaccine/*administration & dosage/adverse effects/genetics/immunology
MH  - Treatment Outcome
MH  - Vaccination/*methods
MH  - Whooping Cough/blood/immunology/*prevention & control
MH  - Young Adult
PMC - PMC5791588
OTO - NOTNLM
OT  - adults
OT  - genetically detoxified PT
OT  - immunogenicity
OT  - persistence
OT  - pertussis
OT  - safety
EDAT- 2017/11/28 06:00
MHDA- 2019/01/12 06:00
PMCR- 2017/11/27
CRDT- 2017/11/28 06:00
PHST- 2017/11/28 06:00 [pubmed]
PHST- 2019/01/12 06:00 [medline]
PHST- 2017/11/28 06:00 [entrez]
PHST- 2017/11/27 00:00 [pmc-release]
AID - 1385686 [pii]
AID - 10.1080/21645515.2017.1385686 [doi]
PST - ppublish
SO  - Hum Vaccin Immunother. 2018 Jan 2;14(1):45-58. doi: 
      10.1080/21645515.2017.1385686. Epub 2017 Nov 27.