PMID- 29140444
OWN - NLM
STAT- MEDLINE
DCOM- 20190412
LR  - 20190412
IS  - 1537-6613 (Electronic)
IS  - 0022-1899 (Print)
IS  - 0022-1899 (Linking)
VI  - 217
IP  - 4
DP  - 2018 Jan 30
TI  - Safety and Immunogenicity of Different Formulations of Norovirus Vaccine 
      Candidate in Healthy Adults: A Randomized, Controlled, Double-Blind Clinical 
      Trial.
PG  - 597-607
LID - 10.1093/infdis/jix572 [doi]
AB  - BACKGROUND: We investigated safety and immunogenicity of 1-2 doses of different 
      bivalent virus-like particle (VLP) norovirus vaccine candidate (NoV) formulations 
      in healthy 18- to 64-year-olds. METHODS: On days 1 and 28, participants (n = 420) 
      randomized to 14 equal groups received intramuscular control vaccine (hepatitis 
      A) or 1 of 11 NoV formulations containing varying dosages of GI.1 and GII.4c 
      genotype VLP antigens with aluminum hydroxide [Al(OH)3], and 0 mug, 15 mug, or 50 
      mug monophosphoryl lipid A (MPL). Immunogenicity was assessed on days 1, 28, 56, 
      208 and 393. Solicited local and systemic reactions were recorded for 7 days, 
      unsolicited adverse events (AEs) until day 56, and serious AEs throughout the 
      trial. RESULTS: All NoV formulations induced similar increases in 
      pan-immunoglobulin, immunoglobulin A, and histo-blood group binding 
      antigen-blocking antibodies by day 56, mostly after 1 dose, that persisted above 
      baseline to day 393. Higher GI.1 content interfered with GII.4c responses, and 
      responses did not benefit from MPL. Overall reactogenicity consisted of mainly 
      mild injection site pain, headache, and fatigue. No vaccine-related serious AEs 
      were reported. CONCLUSIONS: All candidate NoV formulations were well tolerated. 
      Overall, 15 mug GI.1/50 mug GII.4c elicited the best balance of immunogenicity with 
      no clear benefit of MPL, and is the candidate formulation being taken forward in 
      clinical development. CLINICAL TRIALS REGISTRATION: NCT02038907.
CI  - (c) The Author 2017. Published by Oxford University Press for the Infectious 
      Diseases Society of America.
FAU - Leroux-Roels, Geert
AU  - Leroux-Roels G
AD  - Center for Vaccinology, Ghent University and University Hospital, Belgium.
FAU - Cramer, Jakob P
AU  - Cramer JP
AD  - Takeda Pharmaceuticals International AG, Zurich, Switzerland.
FAU - Mendelman, Paul M
AU  - Mendelman PM
AD  - Takeda Vaccines Inc, Boston, Massachusetts.
FAU - Sherwood, James
AU  - Sherwood J
AD  - Takeda Pharmaceuticals International AG, Zurich, Switzerland.
FAU - Clemens, Ralf
AU  - Clemens R
AD  - Takeda Pharmaceuticals International AG, Zurich, Switzerland.
FAU - Aerssens, Annelies
AU  - Aerssens A
AD  - Center for Vaccinology, Ghent University and University Hospital, Belgium.
FAU - De Coster, Ilse
AU  - De Coster I
AD  - Centre for the Evaluation of Vaccination, Vaccine and Infectious Disease 
      Institute, University of Antwerp, Belgium.
FAU - Borkowski, Astrid
AU  - Borkowski A
AD  - Takeda Pharmaceuticals International AG, Zurich, Switzerland.
FAU - Baehner, Frank
AU  - Baehner F
AD  - Takeda Pharmaceuticals International AG, Zurich, Switzerland.
FAU - Van Damme, Pierre
AU  - Van Damme P
AD  - Centre for the Evaluation of Vaccination, Vaccine and Infectious Disease 
      Institute, University of Antwerp, Belgium.
LA  - eng
SI  - ClinicalTrials.gov/NCT02038907
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Infect Dis
JT  - The Journal of infectious diseases
JID - 0413675
RN  - 0 (Antibodies, Viral)
RN  - 0 (Viral Vaccines)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Antibodies, Viral/*blood
MH  - Antibody Formation
MH  - Caliciviridae Infections/*prevention & control
MH  - Double-Blind Method
MH  - Drug Compounding
MH  - Drug-Related Side Effects and Adverse Reactions/epidemiology/pathology
MH  - Female
MH  - Genotype
MH  - Healthy Volunteers
MH  - Humans
MH  - Immunization Schedule
MH  - Injections, Intramuscular
MH  - Male
MH  - Middle Aged
MH  - Norovirus/genetics/immunology
MH  - Viral Vaccines/administration & dosage/*adverse effects/*immunology
MH  - Young Adult
PMC - PMC5853300
OTO - NOTNLM
OT  - adults
OT  - immunogenicity
OT  - norovirus
OT  - reactogenicity
OT  - vaccine
EDAT- 2017/11/16 06:00
MHDA- 2019/04/13 06:00
PMCR- 2017/11/13
CRDT- 2017/11/16 06:00
PHST- 2017/08/15 00:00 [received]
PHST- 2017/11/06 00:00 [accepted]
PHST- 2017/11/16 06:00 [pubmed]
PHST- 2019/04/13 06:00 [medline]
PHST- 2017/11/16 06:00 [entrez]
PHST- 2017/11/13 00:00 [pmc-release]
AID - 4623790 [pii]
AID - jix572 [pii]
AID - 10.1093/infdis/jix572 [doi]
PST - ppublish
SO  - J Infect Dis. 2018 Jan 30;217(4):597-607. doi: 10.1093/infdis/jix572.