PMID- 20732470
OWN - NLM
STAT- MEDLINE
DCOM- 20101230
LR  - 20101011
IS  - 1873-2518 (Electronic)
IS  - 0264-410X (Linking)
VI  - 28
IP  - 43
DP  - 2010 Oct 8
TI  - A phase 1 study of a group B meningococcal native outer membrane vesicle vaccine 
      made from a strain with deleted lpxL2 and synX and stable expression of opcA.
PG  - 6970-6
LID - 10.1016/j.vaccine.2010.08.048 [doi]
AB  - This phase 1 clinical trial assessed the safety and immunogenicity of a native 
      outer membrane vesicle (NOMV) vaccine prepared from a lpxL2(-) synX(-) mutant of 
      strain 44/76 with opcA expression stabilized. Thirty-four volunteers were 
      assigned to one of the three dose groups (25 mcg, 25 mcg with aluminum hydroxide 
      adjuvant, and 50 mcg) to receive three intramuscular injections at 0, 6 and 24 
      weeks. Specific local and systemic adverse events (AEs) were solicited by diary 
      and at visits on days 1, 2, 7 and 14 after each vaccination and at the end of the 
      study at 30 weeks. Blood chemistries, complete blood count, and coagulation 
      studies were measured on each vaccination day and again two days later. Blood for 
      antibody measurements and bactericidal assays were drawn 0, 14, and 42 days after 
      each vaccination. The proportion of volunteers who developed a fourfold or 
      greater increase in serum bactericidal activity (SBA) to the wild-type parent of 
      the vaccine strain with high opcA expression at 6 weeks after the third dose was 
      12/26 (0.46, 95% confidence interval 0.27-0.65). Antibody levels to OpcA were 
      significantly higher in vaccine responders than in non-responders (p=0.008), and 
      there was a trend for higher antibody levels to the lipooligosaccharide (LOS) 
      (p=0.059). Bactericidal depletion assays on sera from volunteers with high-titer 
      responses also indicate a major contribution of anti-OpcA and anti-LOS antibodies 
      to the bactericidal response.These results suggest that genetically modified NOMV 
      vaccines can induce protection against group B meningococcus.
CI  - Copyright (c) 2010 Elsevier Ltd. All rights reserved.
FAU - Keiser, Paul B
AU  - Keiser PB
AD  - Walter Reed Army Institute of Research (WRAIR), Silver Spring, MD, USA. 
      paul.keiser@us.army.mil
FAU - Gibbs, Barnett T
AU  - Gibbs BT
FAU - Coster, Trinka S
AU  - Coster TS
FAU - Moran, E Ellen
AU  - Moran EE
FAU - Stoddard, Mark B
AU  - Stoddard MB
FAU - Labrie, Joseph E 3rd
AU  - Labrie JE 3rd
FAU - Schmiel, Deborah H
AU  - Schmiel DH
FAU - Pinto, Valerian
AU  - Pinto V
FAU - Chen, Ping
AU  - Chen P
FAU - Zollinger, Wendell D
AU  - Zollinger WD
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100821
PL  - Netherlands
TA  - Vaccine
JT  - Vaccine
JID - 8406899
RN  - 0 (Antibodies, Bacterial)
RN  - 0 (Bacterial Outer Membrane Proteins)
RN  - 0 (Bacterial Proteins)
RN  - 0 (Meningococcal Vaccines)
RN  - 0 (OpcA protein, Neisseria meningitidis)
RN  - EC 5.1.- (Racemases and Epimerases)
RN  - EC 5.1.3.- (NeuC protein, Neisseria meningitidis)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Antibodies, Bacterial/blood
MH  - Antibody Formation
MH  - Bacterial Outer Membrane Proteins/genetics/*immunology
MH  - Bacterial Proteins/genetics
MH  - Female
MH  - Humans
MH  - Immunization Schedule
MH  - Male
MH  - Meningitis, Meningococcal/immunology/*prevention & control
MH  - Meningococcal Vaccines/adverse effects/genetics/*immunology
MH  - Middle Aged
MH  - Neisseria meningitidis, Serogroup B/genetics/*immunology
MH  - Racemases and Epimerases/genetics
MH  - Serum Bactericidal Antibody Assay
MH  - Young Adult
EDAT- 2010/08/25 06:00
MHDA- 2010/12/31 06:00
CRDT- 2010/08/25 06:00
PHST- 2010/04/02 00:00 [received]
PHST- 2010/08/04 00:00 [revised]
PHST- 2010/08/07 00:00 [accepted]
PHST- 2010/08/25 06:00 [entrez]
PHST- 2010/08/25 06:00 [pubmed]
PHST- 2010/12/31 06:00 [medline]
AID - S0264-410X(10)01193-X [pii]
AID - 10.1016/j.vaccine.2010.08.048 [doi]
PST - ppublish
SO  - Vaccine. 2010 Oct 8;28(43):6970-6. doi: 10.1016/j.vaccine.2010.08.048. Epub 2010 
      Aug 21.