Defining the optimal formulation and schedule of a candidate toxoid vaccine against Clostridium difficile infection: A randomized Phase 2 clinical trial.
Vaccine
; 34(19): 2170-8, 2016 Apr 27.
Article
in En
| MEDLINE
| ID: mdl-27013431
ABSTRACT
BACKGROUND:
Clostridium difficile, a major cause of nosocomial and antibiotic-associated diarrhea, carries a significant disease and cost burden. This study aimed to select an optimal formulation and schedule for a candidate toxoid vaccine against C. difficile toxins A and B.METHODS:
Randomized, placebo-controlled, two-stage, Phase 2 study in a total of 661 adults aged 40-75 years. Stage I low (50 µg antigen) or high (100 µg antigen) dose with or without aluminum hydroxide (AlOH) adjuvant, or placebo, administered on Days 0-7-30. Stage II Days 0-7-30, 0-7-180, and 0-30-180, using the formulation selected in Stage I through a decision tree defined a priori and based principally on a bootstrap ranking approach. Administration was intramuscular. Blood samples were obtained on Days 0, 7, 14, 30, 60 (Stage I and II), 180, and 210 (Stage II); IgG to toxins A and B was measured by ELISA and in vitro functional activity was measured by toxin neutralizing assay (TNA). Safety data were collected using diary cards.RESULTS:
In Stage I the composite immune response against toxins A and B (percentage of participants who seroconverted for both toxins) was highest in the high dose+adjuvant group (97% and 92% for Toxins A and B, respectively) and was chosen for Stage II. In Stage II the immune response profile for this formulation through Day 180 given on Days 0-7-30 ranked above the other two administration schedules. There were no safety issues.CONCLUSIONS:
The high dose+adjuvant (100 µg antigen+AlOH) formulation administered at 0-7-30 days elicited the best immune response profile, including functional antibody responses, through Day 180 and was selected for use in subsequent clinical trials.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Toxoids
/
Bacterial Vaccines
/
Immunization Schedule
/
Clostridium Infections
Type of study:
Clinical_trials
/
Prognostic_studies
Limits:
Adult
/
Aged
/
Humans
/
Middle aged
Language:
En
Journal:
Vaccine
Year:
2016
Document type:
Article