Scientists develop an oral Covid-19 vaccine

Scientists have developed an oral COVID-19 vaccine, which could provide a more convenient and effective way to combat the SARS-CoV-2 virus, according to a study published in Biology Methods and Protocols by Oxford University Press, US, on Wednesday.

The researchers from Intelligence & Technology Lab, Japan, employed a sublingual vaccine approach designed for under-the-tongue administration. This innovative vaccine contains a crucial component, the spike protein receptor binding domain (RBD) antigen, responsible for the COVID-19 pandemic. To enhance its effectiveness, the vaccine incorporates an adjuvant called poly(I:C), a substance added to the vaccine to help it work more effectively by boosting the immune system's response against the virus.

The scientists said that the best way to neutralise viruses is before they can enter human cells and while they are on the external surface of epithelial cells that line and produce mucus in the lungs, nose, and mouth. A specific class of antibodies known as immunoglobulin A operates in mucus and can disable viruses. However, the production of these specific antibodies for a given virus must be induced by vaccination. Rapid production of immunoglobulin A antibodies through vaccination would better prevent disease, the study said.

Since the coronavirus, like the flu, infects bronchial cells, it is crucial to induce the secretion of virus antigen-specific immunoglobulin A in the mucosa rather than in the blood. Scientists have recently developed vaccines administered via alternative routes, such as nasal or oral administration. These vaccines are more effective in inducing immunoglobulin A than conventional subcutaneous vaccinations, said the scientists. However, nasal vaccines have been known to produce side effects, such as headaches and fever, that affect the central nervous system or lungs.

SARS-CoV-2 shares similarities with the flu virus in that it infects bronchial cells. Researchers stressed the importance of inducing the secretion of virus antigen-specific IgA antibodies in the mucosa lining the respiratory passages rather than in the bloodstream. Recent scientific endeavours have focused on developing vaccines that can be administered through alternative routes, such as nasal and oral administration. These alternative vaccines have demonstrated enhanced efficacy in eliciting IgA responses compared to conventional subcutaneous vaccinations. However, nasal vaccines are known to induce side effects like headaches and fever, often affecting the central nervous system or the lungs, according to scientists.

The primary objective of this study was to assess the vaccine's efficacy using Cynomolgus macaques, a type of monkey employed in scientific research. The sublingual vaccine was crafted with varying doses of the RBD antigen and a consistent amount of poly(I:C) adjuvant. N-acetylcysteine (NAC), a medication used for various purposes, including breaking down mucus in the respiratory system, was used to optimize the delivery of the vaccine to mucosal immune cells lining the respiratory passages, said the scientists.

Results demonstrated the sublingual vaccine’s ability to stimulate a robust mucosal immune response, leading to the production of antigen-specific secretory IgA antibodies in a mucous-like substance found in the nose and mouth. Furthermore, IgG antibodies were detected in the plasma, indicating a strong systemic immune response. A dose-dependent response was observed, suggesting that customising the vaccine's dosage could optimise its efficacy.

The research, scientists said, found little to no allergic response, as indicated by the absence of RBD-specific IgE antibodies in plasma. Importantly, the sublingual vaccination did not produce negative side effects such as inflammation or decreased appetite, the scientists said.

The study suggested that the sublingual Covid-19 vaccine with poly(I:C) adjuvant holds immense promise, effectively triggering mucosal and systemic immune responses in monkeys without causing adverse reactions. Further research is needed to assess safety and efficacy in more detail.

This innovative approach to vaccine administration targets mucosal immunity in the nose and mouth, key entry points for respiratory viruses like SARS-CoV-2. It offers a simpler and more user-friendly alternative to traditional vaccine methods, such as injections. While the study shows promise, additional studies and clinical trials will be necessary to determine the vaccine’s safety and effectiveness in humans, the scientists said.