In the Journals

Single-dose live oral cholera vaccine safely reduces diarrhea

A single-dose live cholera vaccine taken orally appeared to reduce the incidence of diarrhea among adults with no increase in adverse events, according to a recently published study.

“For travelers on short notice to areas of intense cholera transmission, an [oral cholera vaccine] that rapidly confers protection after a single dose would be advantageous,” the researchers wrote. “Such a vaccine would also be useful for reactive mass vaccination to control cholera in explosive unsettled ‘virgin soil’ epidemics where administering more than one dose is logistically challenging.”

PXVX0200 is a reformulation of CVD 103-HgR — a live-attenuated cholera vaccine that was commercially available outside of the United States from 1994 to 2004. Acquired in 2009 by PaxVax, the newer vaccine has since demonstrated early results similar to those reported during trials of its predecessor.

Vaccine efficacious at 10 days, 3 months

To further investigate the vaccine’s efficacy, Wilbur H. Chen, MD, MS, of the Center for Vaccine Development at the University of Maryland School of Medicine, and colleagues enrolled healthy adults aged 18 to 45 years to randomly receive either the PXVX0200 vaccine (n = 95) or placebo (n = 102). Either 10 days or 3 months after vaccination, participants were challenged with wild type Vibrio cholera O1 El Tor Inaba strain N16961. Researchers reported adverse events following inoculation, and collected blood for antibody testing. Participants’ stools were monitored after the challenge for illness and graded by consistency. The primary endpoint for efficacy was the incidence of moderate or severe diarrhea, defined as the passage of at least 3 or 5 liters of loose stool, respectively.

Among volunteers randomly assigned to the vaccine or placebo arms of the trial, 63% were male, and the mean age was 31 years. Sixty-eight participants were challenged with vaccine or placebo at 10 days, and 66 were challenged at 3 months.

The vaccine was well-tolerated, with monitored diarrhea or adverse events insignificantly reduced among those who received immunization vs. those who did not. No serious adverse events were related to the treatment. Antibody seroconversion following vaccination was 90.4%, and no differences were observed among participants with blood type O.

Moderate or significant diarrheal purge was greatly reduced with the vaccine. Compared with the 59.1% rate observed among the placebo arm, only 5.7% (P < .0001) of those challenged at 10 days and 12.1% (P < .0001) of those challenged at 3 months experienced diarrhea. Median volume and stool quantity also were lower (P < .0001) in either group compared with placebo, as was the incidence of fever, nausea/vomiting, abdominal cramping and malaise.

The researchers wrote that these findings, along with the practicality of the single-dose oral vaccine, make PXVX0200 an ideal choice for travelers from countries unaffected by endemic cholera, and also may serve a role in suppressive “explosive” epidemics.

“Our first priority for PXVX0200 is to achieve FDA licensure so that travelers from the [U.S.] can have access to a cholera vaccine,” Chen and colleagues wrote. “If licensed, we would encourage that PXVX0200 be particularly targeted for at-risk travelers to endemic or epidemic regions, hosts especially vulnerable to severe cholera such as individuals of blood group O or with hypochlorhydria, and persons at risk for complications, such as individuals with cardiac or renal impairment.”

Further work needed for long-term protection

In a related editorial, Jason B. Harris, MD, of the division of infectious diseases at Massachusetts General Hospital, reaffirmed the researchers’ belief that the short-term protection offered by the single-dose vaccine would be of exceptional use to travelers. However, he stressed that its efficacy among those living in endemic regions remains unknown and may face several hurdles.

“Is the reformulated version of CVD 103-HgR worth re-evaluating for people living in cholera-endemic areas or who are at risk for epidemic cholera? “Harris wrote. “The answer to this will depend on the cost of the vaccine and the feasibility of delivering it under field conditions.

“While a single-dose vaccine has obvious advantages in the setting of a reactive vaccination campaign, the ability to rapidly produce or stockpile a large supply of the vaccine may also determine whether the vaccine could be used in a humanitarian crisis. While these obstacles may not be insurmountable, it will clearly take a significant commitment to advance CVD 103-HgR to the point where it could be used to help those at greatest risk of dying from cholera.” – by Dave Muoio

Disclosures: Chen and colleagues report full study funding from PaxVax. Harris reports serving on a related data safety and monitoring board as well as on a scientific advisory committee for PaxVax. Please see the full study for a list of all other authors’ relevant financial disclosures.

A single-dose live cholera vaccine taken orally appeared to reduce the incidence of diarrhea among adults with no increase in adverse events, according to a recently published study.

“For travelers on short notice to areas of intense cholera transmission, an [oral cholera vaccine] that rapidly confers protection after a single dose would be advantageous,” the researchers wrote. “Such a vaccine would also be useful for reactive mass vaccination to control cholera in explosive unsettled ‘virgin soil’ epidemics where administering more than one dose is logistically challenging.”

PXVX0200 is a reformulation of CVD 103-HgR — a live-attenuated cholera vaccine that was commercially available outside of the United States from 1994 to 2004. Acquired in 2009 by PaxVax, the newer vaccine has since demonstrated early results similar to those reported during trials of its predecessor.

Vaccine efficacious at 10 days, 3 months

To further investigate the vaccine’s efficacy, Wilbur H. Chen, MD, MS, of the Center for Vaccine Development at the University of Maryland School of Medicine, and colleagues enrolled healthy adults aged 18 to 45 years to randomly receive either the PXVX0200 vaccine (n = 95) or placebo (n = 102). Either 10 days or 3 months after vaccination, participants were challenged with wild type Vibrio cholera O1 El Tor Inaba strain N16961. Researchers reported adverse events following inoculation, and collected blood for antibody testing. Participants’ stools were monitored after the challenge for illness and graded by consistency. The primary endpoint for efficacy was the incidence of moderate or severe diarrhea, defined as the passage of at least 3 or 5 liters of loose stool, respectively.

Among volunteers randomly assigned to the vaccine or placebo arms of the trial, 63% were male, and the mean age was 31 years. Sixty-eight participants were challenged with vaccine or placebo at 10 days, and 66 were challenged at 3 months.

The vaccine was well-tolerated, with monitored diarrhea or adverse events insignificantly reduced among those who received immunization vs. those who did not. No serious adverse events were related to the treatment. Antibody seroconversion following vaccination was 90.4%, and no differences were observed among participants with blood type O.

Moderate or significant diarrheal purge was greatly reduced with the vaccine. Compared with the 59.1% rate observed among the placebo arm, only 5.7% (P < .0001) of those challenged at 10 days and 12.1% (P < .0001) of those challenged at 3 months experienced diarrhea. Median volume and stool quantity also were lower (P < .0001) in either group compared with placebo, as was the incidence of fever, nausea/vomiting, abdominal cramping and malaise.

The researchers wrote that these findings, along with the practicality of the single-dose oral vaccine, make PXVX0200 an ideal choice for travelers from countries unaffected by endemic cholera, and also may serve a role in suppressive “explosive” epidemics.

“Our first priority for PXVX0200 is to achieve FDA licensure so that travelers from the [U.S.] can have access to a cholera vaccine,” Chen and colleagues wrote. “If licensed, we would encourage that PXVX0200 be particularly targeted for at-risk travelers to endemic or epidemic regions, hosts especially vulnerable to severe cholera such as individuals of blood group O or with hypochlorhydria, and persons at risk for complications, such as individuals with cardiac or renal impairment.”

Further work needed for long-term protection

In a related editorial, Jason B. Harris, MD, of the division of infectious diseases at Massachusetts General Hospital, reaffirmed the researchers’ belief that the short-term protection offered by the single-dose vaccine would be of exceptional use to travelers. However, he stressed that its efficacy among those living in endemic regions remains unknown and may face several hurdles.

“Is the reformulated version of CVD 103-HgR worth re-evaluating for people living in cholera-endemic areas or who are at risk for epidemic cholera? “Harris wrote. “The answer to this will depend on the cost of the vaccine and the feasibility of delivering it under field conditions.

“While a single-dose vaccine has obvious advantages in the setting of a reactive vaccination campaign, the ability to rapidly produce or stockpile a large supply of the vaccine may also determine whether the vaccine could be used in a humanitarian crisis. While these obstacles may not be insurmountable, it will clearly take a significant commitment to advance CVD 103-HgR to the point where it could be used to help those at greatest risk of dying from cholera.” – by Dave Muoio

Disclosures: Chen and colleagues report full study funding from PaxVax. Harris reports serving on a related data safety and monitoring board as well as on a scientific advisory committee for PaxVax. Please see the full study for a list of all other authors’ relevant financial disclosures.