Microcontainers for oral vaccine delivery

Research output: Book/ReportPh.D. thesisResearch

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Abstract

The positive impact of vaccines on global human health is second only to clean drinking water, sanitation and hygiene. The emphasis on safety in modern vaccines has motivated use of highly purified antigens to create subunit vaccines. However, these need to be formulated with adjuvants to be effective. Most vaccines require cold chain distribution and are administered via injection by trained healthcare personnel. This is logistically and economically challenging causing many people to be insufficiently vaccinated. Temperature stable oral subunit vaccines are ideal to overcome these challenges, but subunit vaccines require sophisticated oral delivery systems to survive the harsh conditions of the gastrointestinal tract. Vaccines in powder form are most suitable for use with such delivery systems and are often more stable than liquid forms.
In this PhD project, a subunit vaccine formulation was designed using the protein ovalbumin as model antigen and an adjuvant system composed of cubosomes with Quil-A. Spray drying was used to produce a powder that formed the particulate vaccine formulation upon hydration. The vaccine was evaluated in vitro and showed good properties for vaccination. In addition, the antigen was stable in the powder during dry storage at 25ºC for at least 6 months. A design of experiments approach was used to investigate the effects of four important spray drying parameters on key product characteristics. Input-output correlations were established and it was concluded that the method is robust with little impact of the parameters on vaccine-related characteristics thus allowing optimisation to focus on process or powder characteristics. The vaccine was highly immunogenic in vivo in mice when administered by s.c. injection, but ineffective following oral administration.
The main goal of this PhD project was to evaluate microcontainers as oral vaccine delivery system. Microcontainers are small cylindrical polymer-reservoirs with an opening at one end. These were filled with the vaccine and then sealed with a pH-sensitive lid to carry the vaccine safely through the stomach and release it in the intestine. In vitro studies indicated that the microcontainers could protect the vaccine from the challenges of the gastrointestinal tract and deliver it safely to the small intestinal wall. However, they were unable to improve the oral immunogenicity of cubosomes with OVA and Quil-A in vivo.
These results indicate that oral delivery systems such as microcontainers should be used to make vaccines with weak oral immunogenicity more potent rather than to deliver orally ineffective vaccines.
Original languageEnglish
PublisherDTU Nanotech
Number of pages138
Publication statusPublished - 2018

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