DUKORAL® Cholera Vaccine
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). DUKORA suspension and effervescent granules for oral suspension. The World Health Organization (WHO) has prequalified the DUKORAL vaccine. DUKORAL is authorized in Europe, Australia, Canada, Switzerland, New Zealand, Thailand, and the United Kingdom to protect people against cholera and ETEC. The European Medicines Agency (EMA) Dukoral is a vaccine given by mouth to protect people against cholera, a serious disease that causes severe diarrhea. It is used in people aged from 2 years who will be visiting areas with a high risk of cholera. Cholera is caused by the bacterium Vibrio cholerae (V. cholerae), which is caught in contaminated food or water. The vaccine 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 EMA.
Since the 1980s, either killed or live oral cholera vaccines (OCVs) have been developed, and efficacy and effectiveness studies have been conducted. OCV development was initiated at the University of Gothenburg in Sweden using killed whole-cell bacteria. With a vaccine development history of nearly 50 years, both efficacy and effectiveness data on OCV have accumulated.
In the first half of 2023, DUKORAL® sales increased by 197% to €17.1 million, benefiting from the recovery in the private travel markets and price increases. In 2023, cholera outbreaks increased by 20%.
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 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. Check CDC's Travel Health Notices to identify areas with active cholera transmission.
DUKORAL Dosage
Standard primary course for adults and children over six years: two doses; Children 2 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 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 illness or acute 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 2023
Various countries reported cholera outbreaks in August 2023.
DUKORAL News 2023
May 4, 2023 - Valneva SE announced sales increased by 302.6% to €10.2 million in the first quarter of 2023 compared to €2.5 million in 2022, benefitting from the resurgence of the private travel market and as price increases.
March 23, 2023 - The Company announced DUKORAL sales increased to €17.3 million in 2022 compared to €2.4 million in 2021.
March 8, 2023 - OCV vaccinations launched in Syria for about 1.7 million children.
February 24, 2023 - The WHO reported A request for approximately 700,000 doses of OCV was approved, and a vaccination campaign in affected Mozambique districts in Gaza, Niassa, Sofala, and Zambezia provinces.
September 30, 2022 - Cholera Vaccine: Recommendations of the U.S. CDC Advisory Committee on Immunization Practices.
DUKORAL Clinical Studies
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, the protective effectiveness of Dukoral 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.
