Development of a Transgenic Flammulina velutipes Oral Vaccine for Hepatitis B

Summary

Scientists have developed a novel way to create an oral vaccine for hepatitis B using genetically modified enoki mushrooms. Instead of requiring needles and refrigeration, this approach could potentially make vaccines more accessible and easier to distribute worldwide. The researchers successfully modified the mushrooms to produce a hepatitis B protein and showed that pigs eating these mushrooms developed an immune response. Impacts on everyday life: – Could lead to needle-free vaccines that are easier to transport and store – May reduce vaccination costs and increase global access to vaccines – Demonstrates potential for using edible mushrooms as medicine delivery systems – Could make vaccination more acceptable for people afraid of needles – Shows promise for developing other oral vaccines using similar methods

Background

Although vaccinations have saved millions of lives from infectious diseases, full implementation of global vaccination remains challenging due to high costs of conventional vaccinations including mass production, refrigeration, transportation, and administration personnel. Oral vaccines are known to stimulate multiple types of immunity, including mucosal and humoral immunity. While plant-based oral vaccines have been explored, edible mushrooms present unique advantages as vaccine hosts due to fast growth, scaled-up production under controlled conditions and less gene contamination.

Objective

To develop and evaluate a transgenic Flammulina velutipes mushroom expressing the hepatitis B virus surface antigen (HBsAg) as an oral vaccine candidate. The study aimed to obtain stable HBsAg expression through Agrobacterium-mediated transformation followed by fruiting and basidiospore mating, and to assess immunogenicity in pigs.

Results

Three stable transgenic F. velutipes lines were generated expressing HBsAg at levels of 129.3±15.1, 110.9±1.7 and 161.1±8.5 ng/g total soluble protein. In the animal study, two of four pigs fed the transgenic mushrooms developed positive anti-HBsAg antibody responses. One pig showed titers of 5.36 and 14.9 mIU/mL at weeks 10 and 14, while another displayed increasing titers of 9.75, 17.86 and 39.87 mIU/mL at weeks 14, 18 and 20 respectively.

Conclusion

The study successfully generated stable HBsAg-expressing F. velutipes mushrooms through a novel mating scheme and demonstrated their ability to stimulate anti-HBsAg antibody production in pigs when administered orally. This represents the first report showing immunogenicity achieved by feeding transgenic HBsAg mushrooms to pigs, demonstrating the potential application of F. velutipes as an oral vaccine platform.
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