PMID- 31125055
OWN - NLM
STAT- MEDLINE
DCOM- 20201104
LR  - 20201210
IS  - 1537-6591 (Electronic)
IS  - 1058-4838 (Print)
IS  - 1058-4838 (Linking)
VI  - 70
IP  - 1
DP  - 2020 Jan 1
TI  - A Phase 2 Study Evaluating the Safety, Tolerability, and Immunogenicity of Two 
      3-Dose Regimens of a Clostridium difficile Vaccine in Healthy US Adults Aged 65 
      to 85 Years.
PG  - 1-10
LID - 10.1093/cid/ciz153 [doi]
AB  - BACKGROUND: Clostridium difficile causes toxin-mediated nosocomial diarrhea and 
      community-acquired infections; no preventive vaccine is licensed. In this phase 2 
      study, we explored safety, tolerability, and immunogenicity in older US adults of 
      an investigational bivalent C. difficile vaccine that contains equal dosages of 
      genetically and chemically detoxified toxins A and B. METHODS: Conducted from 
      July 2015 through March 2017, 855 healthy adults aged 65-85 years from 15 US 
      centers were randomized 3:3:1 to receive vaccine (100 or 200 mug) or placebo at 0, 
      1, and 6 months (month regimen) or 1, 8, and 30 days (day regimen). Serum toxin 
      A- and B-specific neutralizing antibodies were measured. Participant-reported 
      local reactions (LRs) and systemic events (SEs), adverse events (AEs), serious 
      AEs, newly diagnosed chronic medical conditions, and immediate AEs were recorded. 
      RESULTS: The 200-mug dose level elicited higher immune responses than the 100-microg 
      dose level across regimens. Compared with the day regimen, the month regimen 
      induced stronger and more persistent immune responses that remained elevated 12 
      months after dose 3. Responses peaked at month 7 (month regimen) and day 37 (day 
      regimen). LRs (primarily injection site pain) were more frequent in vaccine 
      recipients than controls; SE frequency was similar across groups. More related 
      AEs were reported in the day regimen group than the month regimen group. 
      CONCLUSIONS: The C. difficile vaccine was safe, well tolerated, and immunogenic 
      in healthy US adults aged 65-85 years. Immune responses were particularly robust 
      in the 200-mug month regimen group. These results support continued vaccine 
      development. CLINICAL TRIALS REGISTRATION: NCT02561195.
CI  - (c) The Author(s) 2019. Published by Oxford University Press for the Infectious 
      Diseases Society of America. All rights reserved. For permissions, e-mail: 
      journals.permissions@oup.com.
FAU - Kitchin, Nicholas
AU  - Kitchin N
AD  - Pfizer Vaccine Clinical Research & Development, Hurley, United Kingdom.
FAU - Remich, Shon A
AU  - Remich SA
AD  - Pfizer Vaccine Research & Development, Collegeville, Pennsylvania.
FAU - Peterson, James
AU  - Peterson J
AD  - Foothill Family Clinic, Salt Lake City, Utah.
FAU - Peng, Yahong
AU  - Peng Y
AD  - Pfizer Vaccine Research & Development, Collegeville, Pennsylvania.
FAU - Gruber, William C
AU  - Gruber WC
AD  - Pfizer Vaccine Research & Development, Pearl River, New York.
FAU - Jansen, Kathrin U
AU  - Jansen KU
AD  - Pfizer Vaccine Research & Development, Pearl River, New York.
FAU - Pride, Michael W
AU  - Pride MW
AD  - Pfizer Vaccine Research & Development, Pearl River, New York.
FAU - Anderson, Annaliesa S
AU  - Anderson AS
AD  - Pfizer Vaccine Research & Development, Pearl River, New York.
FAU - Knirsch, Charles
AU  - Knirsch C
AD  - Pfizer Vaccine Research & Development, Pearl River, New York.
FAU - Webber, Chris
AU  - Webber C
AD  - Pfizer Vaccine Clinical Research & Development, Hurley, United Kingdom.
LA  - eng
SI  - ClinicalTrials.gov/NCT02561195
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Infect Dis
JT  - Clinical infectious diseases : an official publication of the Infectious Diseases 
      Society of America
JID - 9203213
RN  - 0 (Antibodies, Bacterial)
RN  - 0 (Bacterial Vaccines)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies, Bacterial/*blood
MH  - Bacterial Vaccines/*administration & dosage
MH  - Clostridioides difficile/*immunology
MH  - Clostridium Infections/microbiology/*prevention & control
MH  - Drug Administration Schedule
MH  - Female
MH  - Healthy Volunteers
MH  - Humans
MH  - *Immunogenicity, Vaccine
MH  - Male
MH  - United States
MH  - Vaccination/methods
PMC - PMC6912159
OTO - NOTNLM
OT  - Clostridium difficile infection
OT  - United States
OT  - adults
OT  - nosocomial diarrhea
OT  - toxoid vaccine
EDAT- 2019/05/28 06:00
MHDA- 2020/11/05 06:00
PMCR- 2019/05/24
CRDT- 2019/05/25 06:00
PHST- 2018/11/20 00:00 [received]
PHST- 2018/03/18 00:00 [accepted]
PHST- 2019/05/28 06:00 [pubmed]
PHST- 2020/11/05 06:00 [medline]
PHST- 2019/05/25 06:00 [entrez]
PHST- 2019/05/24 00:00 [pmc-release]
AID - 5498282 [pii]
AID - ciz153 [pii]
AID - 10.1093/cid/ciz153 [doi]
PST - ppublish
SO  - Clin Infect Dis. 2020 Jan 1;70(1):1-10. doi: 10.1093/cid/ciz153.