Presentation matters: Buffers, packaging, and delivery devices for new, oral enteric vaccines for infants

Abstract

Oral administration of vaccines is simpler and more acceptable than injection via needle and syringe, particularly for infants (Fig. 1) This route is promising for new vaccines in development against enterotoxigenic Escherichia coli (ETEC) and Shigella that cause childhood diarrhea with devastating consequences in low-resource countries. However, vaccine antigens and adjuvants given orally need buffering against the degradative effects of low stomach pH, and the type and volume of antacid buffer require special attention for infants. In addition, container/closure systems must be compatible with vaccine formulations, protect against water and gas transfer, and have minimal impact on the cold chain. Health care workers in demanding low-resource settings need an administration device that is easy to use, yet will accurately measure and safely deliver the correct vaccine dose. Developers must consider manufacturing capabilities, and immunization program managers want affordable vaccines. As new combination enteric vaccine candidates advance into clinical evaluation, features of the final vaccine presentation—liquid or dry format, diluent, buffer, primary and secondary packaging, and administration device—should be taken into account early in product development to achieve the greatest possible impact for the vaccine.

Cost of goods sold and total cost of delivery for oral and parenteral vaccine packaging formats

“…Key issues include technical compatibility of the selected packaging format with the vaccine, usability and acceptability, and the logistical and programmatic impacts of introducing novel container types [31] , [32] , [33] . For example, certain adjuvants may be susceptible to adhering to polymer containers making them less suitable packaging solutions than glass containers [34] . In addition, the usability of the device is of critical importance to health care workers and can impact the degree of training required [35] , [36] .…”

“…In addition, the usability of the device is of critical importance to health care workers and can impact the degree of training required [35] , [36] . Usability factors such as intuitiveness of use and the ability to easily squeeze and deliver vaccines from both oral and parenteral polymer packaging formats are dependent on the geometry and thickness of the container and viscosity of the vaccine [34] . Stakeholder input on the currently available Uniject™ CPAD has highlighted the simplicity, safety, and cold chain benefits of this preformed polymer container for vaccines [30] , [37] .…”

Anti‐tick and pathogen transmission blocking vaccines

“…With subunit and recombinant vaccines, protection of the antigen from the harsh stomach environment will need to be addressed, and formulations can be tailored to the target species. [116][117][118][119][120] With distribution in the wild, vaccine formulations will need to be protected from environmental factors such as rain and sunshine.…”

“…Formulations can be tailored to aid in oral delivery and immune stimulation. With subunit and recombinant vaccines, protection of the antigen from the harsh stomach environment will need to be addressed, and formulations can be tailored to the target species 116‐120 …”

Preformulation studies with the Escherichia coli double mutant heat-labile toxin adjuvant for use in an oral vaccine

“…Oral vaccines have a number of advantages over traditional parenteral vaccines, including the ability to elicit a protective mucosal immune response, ease of administration, and simplicity of manufacturing compared to vaccines intended for parenteral injection ( Lal and Jarrahian, 2016 ). Oral vaccines also can help facilitate vaccine coverage improvements, as they can sometimes be provided by community health workers outside of formal clinical settings.…”