PMID- 23123106
OWN - NLM
STAT- MEDLINE
DCOM- 20130429
LR  - 20191210
IS  - 1873-2518 (Electronic)
IS  - 0264-410X (Linking)
VI  - 30
IP  - 52
DP  - 2012 Dec 14
TI  - Safety and immunogenicity of pneumococcal protein vaccine candidates: monovalent 
      choline-binding protein A (PcpA) vaccine and bivalent PcpA-pneumococcal histidine 
      triad protein D vaccine.
PG  - 7461-8
LID - S0264-410X(12)01537-X [pii]
LID - 10.1016/j.vaccine.2012.10.076 [doi]
AB  - BACKGROUND: Pneumococcal vaccines based on protein antigens may provide expanded 
      protection against Streptococcus pneumoniae. OBJECTIVE: To evaluate safety and 
      immunogenicity in adults of pneumococcal vaccine candidates comprising S. 
      pneumoniae pneumococcal histidine triad protein D (PhtD) and pneumococcal 
      choline-binding protein A (PcpA) in monovalent and bivalent formulations. 
      METHODS: This was a phase I, randomized, observer-blinded, placebo-controlled, 
      step-wise dose-escalation study. Following a pilot safety study in which 
      participants received one intramuscular injection of either aluminum hydroxide 
      (AH)-adjuvanted PcpA (25 mug) or PhtD-PcpA (10 mug each), participants in the main 
      study received AH-adjuvanted PcpA (25 mug), AH-adjuvanted PhtD-PcpA (10, 25, or 50 
      mug each), unadjuvanted PhtD-PcpA (25 mug each), or placebo as 2 injections 30 days 
      apart. Assignment of successive dose cohorts was made after blinded safety 
      reviews after each dose level. Safety endpoints included rates of solicited 
      injection site and systemic reactions, unsolicited adverse events (AEs), serious 
      AEs (SAEs), and safety laboratory tests. Immunogenicity endpoints included levels 
      of anti-PhtD and anti-PcpA antibodies (ELISA). RESULTS: Six adults 18-50 years of 
      age were included in the pilot study and 125 in the main study. No obvious 
      increases in solicited reactions or unsolicited AEs were reported with escalating 
      doses (adjuvanted vaccine) after either injection, or with repeated 
      administration. Adjuvanted vaccine candidates were associated with a higher 
      incidence of solicited reactions (particularly injection site reactions) than 
      unadjuvanted vaccine candidates. However, no SAE or discontinuation due to an AE 
      occurred. Geometric mean concentrations of anti-PhtD IgG and anti-PcpA IgG 
      increased significantly after injection 2 compared with injection 1 at each dose 
      level. No enhancement of immune responses was shown with adjuvanted vaccine 
      candidates compared with the unadjuvanted vaccine candidate. In the 
      dose-escalating comparison, a plateau effect at the 25 mug dose was observed as 
      measured by geometric mean concentrations and by fold increases. CONCLUSIONS: 
      Promising safety profiles and immunogenicity of these monovalent and bivalent 
      protein vaccine candidates were demonstrated in an adult population 
      (ClinicalTrials.gov registry no. NCT01444339).
CI  - Copyright (c) 2012 Elsevier Ltd. All rights reserved.
FAU - Bologa, Monica
AU  - Bologa M
AD  - Sanofi Pasteur, Toronto, ONT M2R 3T4, Canada. monica@mbpharma.ca
FAU - Kamtchoua, Thierry
AU  - Kamtchoua T
FAU - Hopfer, Robert
AU  - Hopfer R
FAU - Sheng, Xiaohua
AU  - Sheng X
FAU - Hicks, Bryony
AU  - Hicks B
FAU - Bixler, Garvin
AU  - Bixler G
FAU - Hou, Victor
AU  - Hou V
FAU - Pehlic, Vildana
AU  - Pehlic V
FAU - Yuan, Tao
AU  - Yuan T
FAU - Gurunathan, Sanjay
AU  - Gurunathan S
LA  - eng
SI  - ClinicalTrials.gov/NCT01444339
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20121102
PL  - Netherlands
TA  - Vaccine
JT  - Vaccine
JID - 8406899
RN  - 0 (Antibodies, Bacterial)
RN  - 0 (Bacterial Proteins)
RN  - 0 (Carrier Proteins)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (PcpA protein, Streptococcus)
RN  - 0 (Placebos)
RN  - 0 (Pneumococcal Vaccines)
RN  - 0 (Vaccines, Subunit)
RN  - 0 (Vaccines, Synthetic)
RN  - 0 (histidine triad protein)
RN  - EC 3.- (Hydrolases)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Antibodies, Bacterial/blood
MH  - Bacterial Proteins/genetics/*immunology
MH  - Carrier Proteins/genetics/*immunology
MH  - Drug-Related Side Effects and Adverse Reactions/epidemiology/pathology
MH  - Female
MH  - Humans
MH  - Hydrolases/genetics/*immunology
MH  - Immunoglobulin G/blood
MH  - Intracellular Signaling Peptides and Proteins
MH  - Male
MH  - Middle Aged
MH  - Pilot Projects
MH  - Placebos/administration & dosage
MH  - Pneumococcal Vaccines/*administration & dosage/adverse 
      effects/genetics/*immunology
MH  - Single-Blind Method
MH  - Streptococcus pneumoniae/genetics/*immunology
MH  - Vaccines, Subunit/administration & dosage/adverse effects/genetics/immunology
MH  - Vaccines, Synthetic/administration & dosage/adverse effects/genetics/immunology
MH  - Young Adult
EDAT- 2012/11/06 06:00
MHDA- 2013/04/30 06:00
CRDT- 2012/11/06 06:00
PHST- 2012/06/27 00:00 [received]
PHST- 2012/09/24 00:00 [revised]
PHST- 2012/10/20 00:00 [accepted]
PHST- 2012/11/06 06:00 [entrez]
PHST- 2012/11/06 06:00 [pubmed]
PHST- 2013/04/30 06:00 [medline]
AID - S0264-410X(12)01537-X [pii]
AID - 10.1016/j.vaccine.2012.10.076 [doi]
PST - ppublish
SO  - Vaccine. 2012 Dec 14;30(52):7461-8. doi: 10.1016/j.vaccine.2012.10.076. Epub 2012 
      Nov 2.