DUKORAL® Cholera Vaccine Clinical Trials, Dosage, Indication, Side Effects
Valneva SE's DUKORAL® is an oral, inactivated vaccine for preventing diarrhea caused by Vibrio cholerae and/or heat-labile toxin-producing enterotoxigenic Escherichia coli (ETEC). Since the 1980s, either killed or live oral cholera vaccines (OCVs) have been developed, and efficacy and effectiveness studies have been conducted. DUKORAL contains four different inactivated strains (types) of V. cholerae serotype O1 and part of a toxin from one of these strains as active substances, says the European Medicine Agency (EMA). Dukoral is a vaccine given by mouth to protect people against cholera. DUKORAL suspension and effervescent granules for oral suspension. DUKORAL's ATC code: J07AE01, J07AE02, J07AE51.
The World Health Organization (WHO) has prequalified the DUKORAL vaccine. It is authorized in Europe, Australia, Canada, Ireland, New Zealand, Switzerland, Thailand, and the United Kingdom to protect people against cholera and Enterotoxigenic Escherichia coli (ETEC). The EMA (EMEA/H/C/000476) says Dukoral is used in people aged from 2 years who will be visiting areas with a high risk of cholera. The WHO announced on February 12, 2024, that the global demand (74 million) for OCVs has exceeded the supply (38 million). Valneva announced on November 7, 2024, that DUKORAL® sales in the third quarter of 2024 grew 85% year-over-year, as marketing investments resumed in the third quarter following a successful regulatory inspection of the company’s new manufacturing site in Sweden.
France-based Valneva SE's strategy stems from its vision to contribute to a world where no one dies or suffers from a vaccine-preventable disease. Dukoral was initially produced by SBL Vaccine.
DUKORAL Cholera Vaccine Indication
The U.S. CDC recommends vaccination for people traveling to or living in areas of active cholera transmission. In addition, active immunization against disease caused by Vibrio cholerae serogroup O1 is advised for adults and children (2 years) who will be visiting endemic/epidemic areas. But, cholera vaccines are not 100% effective. Check CDC's Travel Health Notices to identify areas with active cholera transmission.
DUKORAL Cholera Vaccine Dosage
DUKORAL is administered orally with a buffer solution that, for adults, requires 150 ml of clean water. The standard primary course for adults and children over six years is two doses; Children to 6 should receive three doses. Doses are to be administered at intervals of at least one week but less than six weeks apart. The primary immunization course should be restarted if more than six weeks have elapsed between doses. Immunization should be completed at least one week before potential exposure to Vibrio cholerae O1.
Each dose of DUKORAL vaccine suspension (3ml) contains a total of 1.25 x 1011 bacteria of the following strains: Vibrio cholerae O1 Inaba, classical biotype (heat inactivated) 31.25 x 109 bacteria, Vibrio cholerae O1 Inaba, El Tor biotype (formalin inactivated) 31.25x 109 bacteria, Vibrio cholerae O1 Ogawa, classical biotype (heat inactivated) 31.25x 109 bacteria, Vibrio cholerae O1 Ogawa, classical biotype (formalin inactivated) 31.25x 109 bacteria. Recombinant cholera toxin B subunit (rCTB) 1mg.
DUKORAL Vaccine Production
Valneva’s global manufacturing network includes three in-house operations to cover the internal and external production of clinical and commercial products. Valneva’s U.S. FDA approved manufacturing site in Livingston is located just outside Edinburgh and is currently dedicated to drug substance production for our viral vaccines. Valneva’s manufacturing site in Solna is just outside Stockholm. The site has a long tradition of vaccine manufacturing and is connected to Sweden’s state-owned vaccine institute. Valneva’s new manufacturing site in Sweden underwent regulatory evaluation and approval in 2024. Along with Valneva’s development center in Vienna (Austria), the Company operates GMP laboratories and facilities for the testing and quality control of Valneva’s commercial and clinical-stage vaccines.
DUKORAL Cholera Vaccine Warnings and Precautions
DUKORAL® confers protection specific to Vibrio cholerae serogroup O1. Immunization does not protect against V. cholerae serogroup O139 or other species of Vibrio. Administration of DUKORAL® should be postponed for subjects suffering from acute gastrointestinal or febrile illness. DUKORAL® is not recommended for use in children less than two years of age. Formaldehyde is used during manufacturing, and trace amounts may be present in the final product. Caution should be taken in subjects with known hypersensitivity to formaldehyde. DUKORAL® contains approximately 1.1 g sodium per dose, which patients should consider on a controlled sodium diet. The vaccine does not provide complete protection.
Cholera Outbreaks
Various countries have reported cholera outbreaks in 2024.
DUKORAL Vaccine News
March 20, 2024 - The Company confirmed that DUKORAL® vaccine sales benefitted from the significant recovery in the private travel markets.
September 30, 2022 - Cholera Vaccine: Recommendations of the U.S. CDC Advisory Committee on Immunization Practices.
DUKORAL Clinical Studies
In September 2023, a Research Article focused on cholera vaccine clinical trials: A cross-sectional analysis of clinical trials registries.
Challenge studies in human volunteers provided the first demonstration of efficacy. The challenge study at the University of Maryland enrolled healthy participants aged 19–35. Participants receiving either WC-BS (with 5 mg of CTB) or WC were given three doses at 2-week intervals. In addition, Cimetidine was administered three hours before receipt of the vaccine in addition to the sodium bicarbonate solution mixed with the vaccine. Vaccinated participants and unvaccinated controls were challenged with 2 × 106 El Tor Inaba V. cholerae (strain N16961) four weeks after completion of the third dose of WC (n = 9) and five weeks after completion of WC-BS (n = 11). The vaccine efficacy of WC was found to be 56%, and for WC-BS, 64% (Table 2). Vaccinated participants in both groups that developed cholera had less severe illness than controls and complete protection from severe diarrhea.
The EMA says the Company presented data from the published literature and results of 3 central studies involving almost 113,000 people to support the use of Dukoral. In all three studies, Dukoral, given in either two or three doses, was compared with a placebo (a dummy vaccine). The studies took place in areas where cholera is found. The primary measure of effectiveness was the 'protective effectiveness' of the vaccine, calculated by comparing the number of people in the studies who developed cholera after receiving Dukoral and a placebo.
The first study involved over 89,000 people in Bangladesh and compared Dukoral with the same vaccine without the toxin and with a placebo. In this study, Dukoral was made using cholera toxin extracted from cholera bacteria instead of the newer recombinant toxin. The protective effectiveness of Dukoral was 85% over six months. Protection lasted for six months in children and two years in adults. In adults, two doses of the vaccine were as effective as 3.
The other two studies compared Dukoral (containing recombinant cholera toxin) with a placebo in over 22,000 people in Peru. In the first of the two studies, Dukoral's protective effectiveness was 85% for the first five months. The people in the second study also received a booster dose 10 to 12 months later. The protective effectiveness of Dukoral after the booster dose was 61% during the second year of follow-up.
