Defining the optimal formulation and schedule of a candidate toxoid vaccine against Clostridium difficile infection: A randomized Phase 2 clinical trial

Autor: Guy, de Bruyn, Jamshid, Saleh, David, Workman, Richard, Pollak, Victor, Elinoff, Neil J, Fraser, Gigi, Lefebvre, Mark, Martens, Richard E, Mills, Richard, Nathan, Miguel, Trevino, Martin, van Cleeff, Ginamarie, Foglia, Ayca, Ozol-Godfrey, Dhaval M, Patel, Patricia J, Pietrobon, Richard, Gesser, Ronald, Blisard
Rok vydání: 2016
Předmět:
Adult
0301 basic medicine
medicine.medical_specialty
medicine.medical_treatment
030106 microbiology
Phases of clinical research
Placebo
Gastroenterology
Immunoglobulin G
03 medical and health sciences
0302 clinical medicine
Adjuvants
Immunologic
Antigen
Immunology and Microbiology(all)
Internal medicine
medicine
Humans
030212 general & internal medicine
Seroconversion
Immunization Schedule
Aged
General Veterinary
General Immunology and Microbiology
biology
Clostridioides difficile
business.industry
Public Health
Environmental and Occupational Health
Clostridium difficile
Middle Aged
Toxoids
veterinary(all)
Antibodies
Bacterial
Bacterial vaccine
Schedule
Infectious Diseases
Formulation
Bacterial Vaccines
Immunology
Clostridium Infections
biology.protein
Molecular Medicine
business
Vaccine
Adjuvant
Zdroj: Vaccine. 34:2170-2178
ISSN: 0264-410X
DOI: 10.1016/j.vaccine.2016.03.028
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: