PMID- 23153437
OWN - NLM
STAT- MEDLINE
DCOM- 20130912
LR  - 20160608
IS  - 1873-2518 (Electronic)
IS  - 0264-410X (Linking)
VI  - 31
IP  - 2
DP  - 2013 Jan 2
TI  - Safety and immunogenicity of the pneumococcal pneumolysin derivative PlyD1 in a 
      single-antigen protein vaccine candidate in adults.
PG  - 327-33
LID - S0264-410X(12)01598-8 [pii]
LID - 10.1016/j.vaccine.2012.11.005 [doi]
AB  - BACKGROUND: Pneumococcal vaccines based on conserved protein antigens have the 
      potential to offer expanded protection against Streptococcus pneumoniae. 
      OBJECTIVE: This study examined the safety and immunogenicity in adults of three 
      doses of a pneumococcal single-antigen protein vaccine candidate formulated with 
      aluminum hydroxide adjuvant and recombinantly derived, highly detoxified, 
      genetically mutated pneumolysin protein (PlyD1). METHODS: This phase I, 
      randomized, placebo-controlled, observer-blinded, dose-escalating study enrolled 
      adults (18-50 years). In a pilot safety study, participants received a single 
      injection of 10 mug PlyD1 and were observed for 24 h. Following review of the 
      pilot safety data, participants were randomized (2:1) to receive two injections 
      of PlyD1 at one of three doses or placebo 30 days apart. Assignment of second 
      injection and successive dose cohorts was made after blinded safety reviews after 
      each injection at each dose level. Safety endpoints included rates of solicited 
      injection site reactions, solicited systemic reactions, unsolicited adverse 
      events (AEs), serious AEs (SAEs), and safety laboratory tests. Immunogenicity 
      endpoints included geometric mean concentrations of anti-PlyD1 IgG as determined 
      by ELISA and functional assessment in an in vitro toxin neutralization assay. 
      RESULTS: The study included a total of 100 participants, including 10 in the 
      pilot study and 90 in the randomized study. None of the participants in the pilot 
      study had SAEs, allergic reactions, or other safety concerns. Ninety participants 
      received two doses of or placebo (n=30) or active vaccine candidate at 10 (n=20), 
      25 (n=20), or 50 mug (n=20). No vaccine-related SAE or discontinuation due to an 
      AE occurred. Most solicited reactions were mild and transient. The most 
      frequently reported solicited reactions were pain at the injection site and 
      myalgia. Antigen-specific IgG levels and functional activity showed dose-related 
      increases. When comparing the three dose levels, a plateau effect was observed at 
      the 25 mug dose. CONCLUSIONS: All dose levels were safe and immunogenic. Repeat 
      vaccination significantly increased the level of anti-PlyD1 antibodies. 
      Functional antibody activity was demonstrated in sera from vaccinated individuals 
      (ClinicalTrials.gov no. NCT01444352).
CI  - Copyright (c) 2012 Elsevier Ltd. All rights reserved.
FAU - Kamtchoua, Thierry
AU  - Kamtchoua T
AD  - Covance Clinical Research Unit AG, SPC 327-10, Lettenweg 118, CH-4123 Allschwil, 
      Switzerland. thierry.kamtchoua@covance.com
FAU - Bologa, Monica
AU  - Bologa M
FAU - Hopfer, Robert
AU  - Hopfer R
FAU - Neveu, David
AU  - Neveu D
FAU - Hu, Branda
AU  - Hu B
FAU - Sheng, Xiaohua
AU  - Sheng X
FAU - Corde, Nicolas
AU  - Corde N
FAU - Pouzet, Catherine
AU  - Pouzet C
FAU - Zimmermann, Gloria
AU  - Zimmermann G
FAU - Gurunathan, Sanjay
AU  - Gurunathan S
LA  - eng
SI  - ClinicalTrials.gov/NCT01444352
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20121112
PL  - Netherlands
TA  - Vaccine
JT  - Vaccine
JID - 8406899
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Bacterial Proteins)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Pneumococcal Vaccines)
RN  - 0 (Streptolysins)
RN  - 0 (plY protein, Streptococcus pneumoniae)
RN  - 5QB0T2IUN0 (Aluminum Hydroxide)
SB  - IM
MH  - Adjuvants, Immunologic
MH  - Adult
MH  - Aluminum Hydroxide/immunology
MH  - Antibody Formation
MH  - Bacterial Proteins/immunology
MH  - Female
MH  - Humans
MH  - Immunoglobulin G/immunology
MH  - Male
MH  - Middle Aged
MH  - Neutralization Tests/methods
MH  - Pilot Projects
MH  - Pneumococcal Vaccines/*adverse effects/*immunology
MH  - Streptococcus pneumoniae/*immunology
MH  - Streptolysins/*immunology
MH  - Young Adult
EDAT- 2012/11/17 06:00
MHDA- 2013/09/13 06:00
CRDT- 2012/11/17 06:00
PHST- 2012/06/29 00:00 [received]
PHST- 2012/10/24 00:00 [revised]
PHST- 2012/11/04 00:00 [accepted]
PHST- 2012/11/17 06:00 [entrez]
PHST- 2012/11/17 06:00 [pubmed]
PHST- 2013/09/13 06:00 [medline]
AID - S0264-410X(12)01598-8 [pii]
AID - 10.1016/j.vaccine.2012.11.005 [doi]
PST - ppublish
SO  - Vaccine. 2013 Jan 2;31(2):327-33. doi: 10.1016/j.vaccine.2012.11.005. Epub 2012 
      Nov 12.