Formulation of recombinant Lactococcus lactis as an oral vaccine candidate for COVID-19

Background: Lactococcus lactis is a promising oral vaccine carrier. However, to improve the stability of the bacteria, the freeze-drying method and formulation need to be optimised. Objective: To develop a formulation of oral recombinant food-grade Lactococcus lactis as a candidate oral vaccine for coronavirus disease 2019 (COVID-19). Method: To preserve bacteria during storage, a combination of skim milk, trehalose, and sucrose concentrations was adjusted. The impacts of the freeze-drying procedure were investigated using a bacterial viability test, and bacterial morphology was assessed using scanning electron microscopy. Bacteria produced from the freeze-drying technique were combined with excipients to create granules, tablets, and capsules. After one month of storage, the bacterial viability of each product was assessed after one-month storage in 4°C and 25°C, and physicochemical testing was conducted on each product. Results: The cryoprotectant formula containing 8% of skim milk and 7.5% of sucrose protected the bacteria the most from the freeze-drying process. The tablets and capsules complied with current specifications, including disintegration test, tablet hardness, capsule weight uniformity, and bacteria viability. Conclusion: Among the products, tablets stored for one month at 4°C had the best bacterial viability. This study demonstrated the potential to develop and administer an easy-to-use oral COVID-19 vaccine candidate using L. lactis.