Radix Astragali polysaccharide RAP: an ideal intestinal M cell-targeted oral vaccine carrier and immunostimulant?

An oral vaccine could be key to fighting pandemics. In our fresh experience of fighting against COVID-19, the timely use of vaccines is limited by the huge logistical burden, concerns of needle-associated side effects, and complicated manufacturering procedure, which, in turn, affected the vaccination efficiency finally. An oral vaccine that can be mailed worldwide and taken anytime anywhere will be a preferable solution for the next pandemic wave.

The major difficulty in developing oral vaccines is their poor accessibility to immune cells, so the efforts to develop oral vaccines focus on delivering the antigen in a form that maximizes the chances of its uptake by M cells of Peyer’s patches (PPs, the major intestinal mucosal immune organ) for initiation of the immune response. Besides, the oral tolerance and low immunogenicity of vaccines are also difficulties to solve, where adjuvants are needed.

In our preliminary studies, we found Radix Astragali polysaccharide RAP a promising vaccine material. Orally-dosed RAP quickly entered PPs via M-cell uptake which was mediated by GP2 as verified on gen-deficient mice. Besides, RAP remained indigestive and intact in the gastric intestinal tract, showing sufficient stability and tolerance to the acidic and biodegradable environment. More importantly, M-cell targeted transport of RAP also applied to human subjects. It is suggested that RAP could be an efficient vaccine carrier. Further investigation indicated that after entering PPs, RAP directly and specifically targeted Dendric cells which triggered a series of immune responses in PPs
in terms of inducing signaling pathways and cytokine production, DC/B cell activation, and IgM/IgA production. RAP’s additional potential as immunostimulant was therefore highlighted. So we hypothesize that RAP-nanocapsule could be a promising oral vaccine dual-function adjuvant of both carrier and immunostimulant.

To test this hypothesis, the current project aims 1) to systematically evaluate RAPinduced immunogenicity and determine the molecular mechanism; 2) to determine if RAP-nanocapsule can specifically deliver antigens (e.g. OVA) to intestinal lymphatic system and characterize the properties of RAP-based oral vaccine.

Whether RAP’s potential as vaccine carrier and immunostimulant is verified, financial investment will be sought to further test the efficacy on animal models and in clinic. RAP’s success may generate a new broad-spectrum platform for designing effective oral vaccines with clearly determined molecular mechanism, which will directly benefit the R&D of oral vaccines and therefore the fight against pandemics such as COVID19, and Ebola. The medical use of Chinese medicine polysaccharides will be also extended, which may facilitate, to some extent, the modernization of Chinese medicines.