PMID- 37977942
OWN - NLM
STAT- MEDLINE
DCOM- 20240102
LR  - 20240102
IS  - 1873-2518 (Electronic)
IS  - 0264-410X (Linking)
VI  - 41
IP  - 50
DP  - 2023 Dec 7
TI  - A phase 3 study evaluating the lot consistency, immunogenicity, safety, and 
      tolerability of a Clostridioides difficile vaccine in healthy adults 65 to 85 
      years of age.
PG  - 7548-7559
LID - S0264-410X(23)01296-3 [pii]
LID - 10.1016/j.vaccine.2023.11.003 [doi]
AB  - BACKGROUND: A toxoid-based Clostridioides difficile vaccine is currently in 
      development. Here, we report lot-to-lot consistency, immunogenicity, safety, and 
      tolerability of 3 C difficile vaccine doses in healthy older adults. METHODS: 
      This phase 3, placebo-controlled study randomized (1:1:1:1) healthy adults 65 to 
      85 years of age to 1 of 3 C difficile vaccine lots or placebo. Participants 
      received C difficile vaccine (200 mug total toxoid) or placebo (Months 0, 1, 6). 
      The primary immunogenicity objective was lot-to-lot consistency (2-sided 95 % CIs 
      within 0.5 and 2 for comparisons of geometric mean concentration [GMC] ratios) 
      for toxins A- and B-specific neutralizing antibody levels 1 month after Dose 3. 
      Safety outcomes included local reactions and systemic events </=7 days after 
      vaccination, adverse events (AEs), and serious AEs (SAEs). RESULTS: Of 1317 
      enrolled participants, 1218 completed the study. C difficile vaccine 
      immunogenicity was consistent across lots, with neutralizing antibody responses 
      1 month after Dose 3 for both toxin A (GMC [95 % CI]: lot 1, 878.8 [786.3, 
      982.2]; lot 2, 873.0 [779.2, 978.1]; lot 3, 872.9 [782.6, 973.5]) and toxin B 
      (lot 1, 5823.9 [5041.0, 6728.4]; lot 2, 5462.8 [4733.4, 6304.7]; lot 3, 5426.0 
      [4724.4, 6231.8]). Two-sided 95 % CIs for GMC ratios were within 0.5 and 2 for 
      toxins A and B, indicating lot-to-lot consistency was achieved. C difficile 
      vaccine was well tolerated, with similar rates of local reactions and systemic 
      events among vaccine lots. AE and SAE rates were similar across C difficile 
      vaccine (36.5 % and 4.5 %, respectively) and placebo (35.3 % and 6 %). 
      CONCLUSIONS: Three doses (Months 0,1,6) of toxoid-based C difficile vaccine 
      induced robust neutralizing antibody responses and were well tolerated in healthy 
      participants 65 to 85 years of age. Lot-to-lot consistency was excellent, 
      indicating the manufacturing process for this C difficile vaccine formulation was 
      well controlled. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: 
      NCT03579459.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Christensen, Shane
AU  - Christensen S
AD  - J. Lewis Research, Salt Lake City, UT, USA.
FAU - Bouguermouh, Salim
AU  - Bouguermouh S
AD  - Pfizer Inc, Pearl River, NY, USA. Electronic address: 
      salim.bouguermouh@pfizer.com.
FAU - Ilangovan, Kumar
AU  - Ilangovan K
AD  - Pfizer Inc, Collegeville, PA, USA.
FAU - Pride, Michael W
AU  - Pride MW
AD  - Pfizer Inc, Pearl River, NY, USA.
FAU - Webber, Chris
AU  - Webber C
AD  - Pfizer Ltd, Hurley, UK.
FAU - Lockhart, Stephen P
AU  - Lockhart SP
AD  - Pfizer Ltd, Hurley, UK.
FAU - Shah, Rupal
AU  - Shah R
AD  - Pfizer Inc, Pearl River, NY, USA.
FAU - Kitchin, Nicholas
AU  - Kitchin N
AD  - Pfizer Ltd, Hurley, UK.
FAU - Lamberth, Erik
AU  - Lamberth E
AD  - Pfizer Inc, Collegeville, PA, USA.
FAU - Zhang, Haiying
AU  - Zhang H
AD  - Pfizer Inc, Collegeville, PA, USA.
FAU - Gao, Qi
AU  - Gao Q
AD  - Pfizer Inc, Collegeville, PA, USA.
FAU - Brock, Linda
AU  - Brock L
AD  - Pfizer Inc, Pearl River, NY, USA.
FAU - Anderson, Annaliesa S
AU  - Anderson AS
AD  - Pfizer Inc, Pearl River, NY, USA.
FAU - Gruber, William C
AU  - Gruber WC
AD  - Pfizer Inc, Pearl River, NY, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT03579459
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20231117
PL  - Netherlands
TA  - Vaccine
JT  - Vaccine
JID - 8406899
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (Antibodies, Viral)
RN  - 0 (Bacterial Vaccines)
RN  - 0 (Toxoids)
SB  - IM
MH  - Aged
MH  - Humans
MH  - Antibodies, Neutralizing
MH  - Antibodies, Viral
MH  - Bacterial Vaccines
MH  - Clostridioides
MH  - *Clostridioides difficile
MH  - Double-Blind Method
MH  - Immunogenicity, Vaccine
MH  - Toxoids
MH  - Aged, 80 and over
OTO - NOTNLM
OT  - CDI
OT  - Clostridiodes difficile infection
OT  - Clostridioides difficile
OT  - Nosocomial diarrhea
OT  - Toxin neutralization assay
OT  - Toxoid vaccine
COIS- Declaration of Competing Interest The authors declare the following financial 
      interests/personal relationships which may be considered as potential competing 
      interests: SC: has no conflicts of interest to declare. SB, KI, MWP, CW, SPL, RS, 
      NK, EL, HZ, QG, LB, ASA, WCG are employees of Pfizer and may own stock or stock 
      option.
EDAT- 2023/11/18 11:41
MHDA- 2023/12/04 12:42
CRDT- 2023/11/17 22:02
PHST- 2023/07/24 00:00 [received]
PHST- 2023/10/31 00:00 [revised]
PHST- 2023/11/01 00:00 [accepted]
PHST- 2023/12/04 12:42 [medline]
PHST- 2023/11/18 11:41 [pubmed]
PHST- 2023/11/17 22:02 [entrez]
AID - S0264-410X(23)01296-3 [pii]
AID - 10.1016/j.vaccine.2023.11.003 [doi]
PST - ppublish
SO  - Vaccine. 2023 Dec 7;41(50):7548-7559. doi: 10.1016/j.vaccine.2023.11.003. Epub 
      2023 Nov 17.