ABSTRACT. PXVX0200 is an oral cholera vaccine that is approved for use by the U.S. Food and Drug Administration and European Medicines Agency under the tradename Vaxchora. The vaccine is supplied as two packets, one containing buffer component and the other the active component, that are mixed with water and ingested. The aim of this study was to develop vaccine preparation methods that are appropriate for administering PXVX0200 to children. Developing oral liquid medication for children has unique challenges, including administration volume and palatability. These challenges were addressed by preparing PXVX0200 in different volumes and testing the potency of the vaccine in the presence of sweeteners, flavorings, and food and drinks. Vaccine potency, defined as colony-forming units/dose, was used to determine the compatibility of PXVX0200 with different vaccine preparation methods. We found that the reconstitution volume can be reduced from 100 to 50 mL to accommodate children aged 2 to 6 years and to 10 mL for children aged 6 months to 2 years, as long as the buffer concentration is the same as for the approved (100 mL) dose. Sucrose or stevia sweeteners may also be added without affecting the vaccine potency. Reconstitution in juices or foods was challenging because of effervescence caused by bicarbonate in the buffer component. An alternate preparation method was developed for reconstitution in baby formula. Vaccine preparation methods to make PXVX0200 appropriate for pediatric administration will facilitate administration of the vaccine to improve compliance and protect children from cholera infection while traveling.

Vaccination is a well-established means for prevention and spread of disease in people traveling abroad. Although vaccines to diseases such as cholera are recommended by world health agencies, they are seldom required even when traveling to endemic regions. Consequences of noncompliance can affect traveler’s health and spread diseases to new regions, as occurred in Haiti in 2010 when United Nations peacekeepers from Nepal, where a cholera outbreak was underway, introduced the disease to the region. Steps to increase vaccine recommendation compliance should therefore be an integral part of vaccine development. PXVX0200 contains Center for Vaccine Development 103-HgR live, attenuated recombinant Vibrio cholerae vaccine strain, and is indicated for single-dose immunization against the bacteria that causes cholera. It is supplied as one buffer and one active component packet to be mixed into water and ingested. Administration instructions are designed to be “user friendly” with flexibility for self-administration, thus promoting compliance. Studies to support self-administration were conducted to cover stability of the vaccine outside of normal storage conditions, potency in case of misadministration, and disposal procedures to minimize environmental impact. The principal findings showed that the stability of vaccine was maintained under conditions allowing for transport times and temperature conditions as well as when misadministration errors were made. Finally, the vaccine was effectively neutralized with hot water and soap to prevent bacterial environmental contamination in the event of an accidental spill. The conclusion is that PXVX0200 oral vaccine is stable, easy to formulate and dispose of, and is amenable to self-administration.

CVD 103-HgR live, attenuated oral cholera vaccine strain is indicated for single dose immunization against Vibrio cholerae, the causative agent for cholera. The vaccine packets containing buffer powder and lyophilized CVD 103-HgR are reconstituted in water and consumed. Studies were performed to explore the viability of CVD 103-HgR in drinking waters from common sources. CVD 103-HgR vaccine was reconstituted in bottled and tap waters from the United States and Europe, and viability was measured via colony forming units assay. Chemical analysis of select water samples was used to identify chemicals that have a negative effect on CVD 103-HgR viability. CVD 103-HgR titers were stable in all bottled waters tested, including purified bottled water, bottled spring water, and sparkling waters. However, tap water from certain cities in the US and Europe affected viability and are not compatible with vaccine. Water chemistry revealed that these tap waters contained copper, likely leached from copper plumbing. These studies give high confidence in the stability of CVD 103-HgR reconstituted in a variety of bottled waters. Waters containing copper, including tap water, should not be used to reconstitute CVD 103-HgR strain oral vaccine due to the common use of copper plumbing.