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on a blood agar plate
Credit: CDC
BOSTON—Results of a phase 2 study suggest an investigational vaccine may be able to prevent Clostridium difficile infection (CDI).
The vaccine generated an immune response against C difficile toxins A and B. And adverse reactions were generally mild and of short duration.
Researchers presented these results at the 114th General Meeting of the American Society for Microbiology. The study was sponsored by Sanofi, the company developing the vaccine.
“C diff infection threatens the many people who frequently use antibiotics, as well as older hospitalized patients and residents in long-term healthcare facilities,” said study investigator Jamshid Saleh, MD of the Northern California Clinical Research Center in Redding, California.
“It would be great if we could offer patients a way to help prevent this contagious and debilitating disease versus just treating it after it happens.”
To find out if Sanofi’s vaccine would do the job, Dr Saleh and his colleagues conducted a randomized, multicenter trial split into 2 stages.
The first stage, conducted with 455 volunteers, was placebo-controlled, double-blind, and designed for dose and formulation selection. The second stage, which included 206 additional volunteers, was designed to compare the dose and formulation chosen in the first stage against 2 alternate dosing schedules.
Volunteers ranged in age from 40 to 75 years and were at risk of CDI due to impending hospitalization or residence in a long-term healthcare facility.
In stage 1, volunteers were randomized into 1 of 5 study groups: high-dose or low-dose vaccine, either with or without adjuvant, or placebo. Each formulation was administered on days 0, 7, and 30.
Researchers measured immune responses using both enzyme linked immunosorbent assay (ELISA), which assesses antitoxin A and B immunoglobulin G (IgG) concentrations, and toxin neutralization activity (TNA), which measures antitoxin A and B neutralizing activity.
Composite ELISA ranking analysis determined that the high-dose plus adjuvant vaccine formulation (group 3) generated the greatest immune response over a 60-day period. ELISA results also showed a 4-fold increase in the development of detectable antibodies for both toxins A and B.
So the researchers selected the high-dose plus adjuvant vaccine formulation for further study in stage 2 of the trial. They compared its use across 3 schedules: days 0, 7, and 30 (group 3, n=101); days 0, 7, and 180 (group 6, n=103); and days 0, 30, and 180 (group 7, n=103). The team analyzed subjects on days 0, 7, 14, 30, 60, 180, and 210.
There were increased immune responses in all vaccine groups and with each dose, according to ELISA and TNA. Overall, group 3 demonstrated the most favorable immune profile over the 30-, 60- and 180-day periods, particularly in volunteers aged 65-75 years.
The safety profile of all vaccine doses was deemed acceptable throughout the study. Reactions were monitored until day 210 and were generally grade 1, of short duration, did not lead to study discontinuation, and were not considered clinically significant.
“Sanofi Pasteur’s investigational vaccine stimulates a person’s immune system to fight C diff toxins upon exposure and, ultimately, may help prevent a future CDI from occurring,” Dr Saleh said.
“Like other toxoid vaccines—such as tetanus, diphtheria, and whooping cough—this investigational vaccine targets the symptom-causing toxins generated by C diff bacteria and could be an important public health measure to help protect individuals from CDI.”
Based on the phase 2 results, researchers started a phase 3 trial in August 2013. 
on a blood agar plate
Credit: CDC
BOSTON—Results of a phase 2 study suggest an investigational vaccine may be able to prevent Clostridium difficile infection (CDI).
The vaccine generated an immune response against C difficile toxins A and B. And adverse reactions were generally mild and of short duration.
Researchers presented these results at the 114th General Meeting of the American Society for Microbiology. The study was sponsored by Sanofi, the company developing the vaccine.
“C diff infection threatens the many people who frequently use antibiotics, as well as older hospitalized patients and residents in long-term healthcare facilities,” said study investigator Jamshid Saleh, MD of the Northern California Clinical Research Center in Redding, California.
“It would be great if we could offer patients a way to help prevent this contagious and debilitating disease versus just treating it after it happens.”
To find out if Sanofi’s vaccine would do the job, Dr Saleh and his colleagues conducted a randomized, multicenter trial split into 2 stages.
The first stage, conducted with 455 volunteers, was placebo-controlled, double-blind, and designed for dose and formulation selection. The second stage, which included 206 additional volunteers, was designed to compare the dose and formulation chosen in the first stage against 2 alternate dosing schedules.
Volunteers ranged in age from 40 to 75 years and were at risk of CDI due to impending hospitalization or residence in a long-term healthcare facility.
In stage 1, volunteers were randomized into 1 of 5 study groups: high-dose or low-dose vaccine, either with or without adjuvant, or placebo. Each formulation was administered on days 0, 7, and 30.
Researchers measured immune responses using both enzyme linked immunosorbent assay (ELISA), which assesses antitoxin A and B immunoglobulin G (IgG) concentrations, and toxin neutralization activity (TNA), which measures antitoxin A and B neutralizing activity.
Composite ELISA ranking analysis determined that the high-dose plus adjuvant vaccine formulation (group 3) generated the greatest immune response over a 60-day period. ELISA results also showed a 4-fold increase in the development of detectable antibodies for both toxins A and B.
So the researchers selected the high-dose plus adjuvant vaccine formulation for further study in stage 2 of the trial. They compared its use across 3 schedules: days 0, 7, and 30 (group 3, n=101); days 0, 7, and 180 (group 6, n=103); and days 0, 30, and 180 (group 7, n=103). The team analyzed subjects on days 0, 7, 14, 30, 60, 180, and 210.
There were increased immune responses in all vaccine groups and with each dose, according to ELISA and TNA. Overall, group 3 demonstrated the most favorable immune profile over the 30-, 60- and 180-day periods, particularly in volunteers aged 65-75 years.
The safety profile of all vaccine doses was deemed acceptable throughout the study. Reactions were monitored until day 210 and were generally grade 1, of short duration, did not lead to study discontinuation, and were not considered clinically significant.
“Sanofi Pasteur’s investigational vaccine stimulates a person’s immune system to fight C diff toxins upon exposure and, ultimately, may help prevent a future CDI from occurring,” Dr Saleh said.
“Like other toxoid vaccines—such as tetanus, diphtheria, and whooping cough—this investigational vaccine targets the symptom-causing toxins generated by C diff bacteria and could be an important public health measure to help protect individuals from CDI.”
Based on the phase 2 results, researchers started a phase 3 trial in August 2013.
on a blood agar plate
Credit: CDC
BOSTON—Results of a phase 2 study suggest an investigational vaccine may be able to prevent Clostridium difficile infection (CDI).
The vaccine generated an immune response against C difficile toxins A and B. And adverse reactions were generally mild and of short duration.
Researchers presented these results at the 114th General Meeting of the American Society for Microbiology. The study was sponsored by Sanofi, the company developing the vaccine.
“C diff infection threatens the many people who frequently use antibiotics, as well as older hospitalized patients and residents in long-term healthcare facilities,” said study investigator Jamshid Saleh, MD of the Northern California Clinical Research Center in Redding, California.
“It would be great if we could offer patients a way to help prevent this contagious and debilitating disease versus just treating it after it happens.”
To find out if Sanofi’s vaccine would do the job, Dr Saleh and his colleagues conducted a randomized, multicenter trial split into 2 stages.
The first stage, conducted with 455 volunteers, was placebo-controlled, double-blind, and designed for dose and formulation selection. The second stage, which included 206 additional volunteers, was designed to compare the dose and formulation chosen in the first stage against 2 alternate dosing schedules.
Volunteers ranged in age from 40 to 75 years and were at risk of CDI due to impending hospitalization or residence in a long-term healthcare facility.
In stage 1, volunteers were randomized into 1 of 5 study groups: high-dose or low-dose vaccine, either with or without adjuvant, or placebo. Each formulation was administered on days 0, 7, and 30.
Researchers measured immune responses using both enzyme linked immunosorbent assay (ELISA), which assesses antitoxin A and B immunoglobulin G (IgG) concentrations, and toxin neutralization activity (TNA), which measures antitoxin A and B neutralizing activity.
Composite ELISA ranking analysis determined that the high-dose plus adjuvant vaccine formulation (group 3) generated the greatest immune response over a 60-day period. ELISA results also showed a 4-fold increase in the development of detectable antibodies for both toxins A and B.
So the researchers selected the high-dose plus adjuvant vaccine formulation for further study in stage 2 of the trial. They compared its use across 3 schedules: days 0, 7, and 30 (group 3, n=101); days 0, 7, and 180 (group 6, n=103); and days 0, 30, and 180 (group 7, n=103). The team analyzed subjects on days 0, 7, 14, 30, 60, 180, and 210.
There were increased immune responses in all vaccine groups and with each dose, according to ELISA and TNA. Overall, group 3 demonstrated the most favorable immune profile over the 30-, 60- and 180-day periods, particularly in volunteers aged 65-75 years.
The safety profile of all vaccine doses was deemed acceptable throughout the study. Reactions were monitored until day 210 and were generally grade 1, of short duration, did not lead to study discontinuation, and were not considered clinically significant.
“Sanofi Pasteur’s investigational vaccine stimulates a person’s immune system to fight C diff toxins upon exposure and, ultimately, may help prevent a future CDI from occurring,” Dr Saleh said.
“Like other toxoid vaccines—such as tetanus, diphtheria, and whooping cough—this investigational vaccine targets the symptom-causing toxins generated by C diff bacteria and could be an important public health measure to help protect individuals from CDI.”
Based on the phase 2 results, researchers started a phase 3 trial in August 2013.