By Marie Rosenthal, MS
A single high-dose CVD 103-HgR live oral cholera vaccine (Vaxcora, PaxVax) has shown effectiveness in controlling cholera epidemics in developing countries.
“Immunization with a single-dose cholera vaccine that could rapidly protect people in developing countries who have not previously been exposed to cholera would be a significant asset in helping control outbreaks and lower mortality rates,” said Myron M. Levine, MD, DTPH, a professor and an associate dean for Global Health, Vaccinology and Infectious Diseases, and the founder and former director of the Center for Vaccine Development, University of Maryland School of Medicine, in Baltimore. “Given the highly encouraging results, we recommend that high-dose CVD 103-HgR is evaluated in developing countries as a matter of priority,” added Dr. Levine, who was the lead author of the study (Clin Vaccine Immunol 2017;24:12-13).
This phase 2 clinical trial, in Mali, compared the vibriocidal responses of participants 18 to 45 years of age, who were randomly assigned to ingest a single standard dose (108 colony-forming units [cfu]) or a high dose (109 cfu) of CVD 103-HgR with buffer, or two doses of an inactivated cholera vaccine that is currently recommended by the World Health Organization. For purposes of blinding, CVD 103-HgR recipients also received a placebo two weeks before or after ingesting the study vaccine.
The primary outcomes were seroconversion between baseline and 14 days after live cholera vaccine ingestion and following the first and second doses of inactivated vaccine.
By day 14, the rate of seroconversion after ingestion of a single high dose of CVD 103-HgR was 83.3% versus 71.7% for a standard dose of CVD 103-HgR, which is the dose that is currently approved in the United States for use in travelers, and 56.0% for a single dose of the inactivated vaccine.
By day 28 (14 days after the second dose of the inactivated cholera vaccine), the rate of seroconversion was 89.4% for a single high dose of CVD 103-HgR versus 83.7% and 76.1% for a standard dose of the live vaccine and for the second dose of the inactivated vaccine, respectively.
All formulations evaluated in this trial were well tolerated.
CVD 103-HgR is an oral vaccine indicated for active immunization against disease caused by Vibrio cholerae serogroup O1. The FDA approved its use in June 2016, as the only vaccine available in the United States for active immunization against cholera. In May 2017, the Advisory Committee on Immunization Practices recommended CVD 103-HgR for adults traveling to an area of active cholera transmission.
Cholera, an intestinal infection transmitted by ingestion of food and water contaminated with V. cholerae, presents a global public health challenge. It can cause fever, diarrhea, vomiting, painful cramping and dehydration. In severe cases, patients pass large amounts of diarrhea—up to 1 L per hour—that causes rapid dehydration and can be fatal if left untreated. Cholera transmission is endemic in many areas of Africa, Asia and the Caribbean. There are an estimated 3 million cases of cholera worldwide every year. Outbreaks, such as those recently seen in Yemen, Bangladesh and Haiti, continue to have devastating effects on public health and can cause massive social disruption and high rates of death, especially in developing countries that lack infrastructure, modern sanitation and access to clean water.
Although there is a WHO stockpile of cholera vaccines for control of outbreaks, currently available vaccines are two-dose regimens administered two weeks apart. While these vaccines have been useful in reducing seasonal increases in cholera rates in areas where this disease is endemic and where targeting of populations is possible, there are logistical challenges in providing the second dose.