Chitosan as antigen platform for pneumococcal vaccines

Chitosan shows great potential as part of drug release systems of orally administered drug formulations. Another interesting use is as an antigen platform for vaccines. We present an article in which pneumococcal membrane protein-loaded chitosan capsules were prepared and evaluated for their efficacy for a nasally administered vaccine.

CHITOSAN-BASED NANOSYSTEM AS PNEUMOCOCCAL VACCINE PLATFORM

A chitosan‑based nanosystem as pneumococcal vaccine delivery platform. Sandra Robla, Maruthi Prasanna, Rubén Varela‑Calviño, Cyrille Grandjean, Noemi Csaba. Drug Delivery and Translational Research, 11, 581–597, 2021, https://doi.org/10.1007/s13346-021-00928-3.

Streptococcus pneumoniae infects the upper respiratory tract and can cause pneumonia, meningitis or sepsis. Infants, seniors and immunocompromised persons are particularly at risk from pneumococci.
The surface proteins and capsular polysaccharides of S. pneumoniae located on the cell membrane provide a target for vaccines. Different capsular polysaccharides can distinguish between more than 96 serotypes of S. pneumoniae. Cell surface proteins, on the other hand, are less variable than capsular polysaccharides.
Current vaccines are based on the capsular polysaccharides and only lead to immunization against certain serotypes. Alternatively, vaccines could be based on the less variable membrane proteins, such as pneumococcal surface adhesin A (PsaA). Intranasal immunizations are non-mucosal and elicit systemic immune responses. Due to its good mucoadhesion, biocompatibility and biodegradability, chitosan promises high potential as a vaccine platform.
The nanocapsules were studied for their physicochemical properties and association efficiency during fabrication. Subsequently, the morphology of the particles was analyzed by electron microscopy and the stability of the nanocapsules was studied in vitro using simulated nasal fluid. In addition, the release of antigen from the nanocapsules and toxicity were also analyzed in vitro. Finally, the interactions with immune cells were investigated.

RESULTS

• produced nanocapsules were monodisperse and between 245 - 266 nm in size
• association of more PsaA antigens by covalent binding to chitosan nanocapsules
• nanocapsules were stable in simulated nasal fluid
• no change in physicochemical properties of nanocapsules after lyophilization followed by reconstitution
• antigen release in two phases, first rapid release of half of the charged antigens, followed by delayed and slow release of the remaining charge
• antigen release occurred by covalent binding to chitosannanocapsules for a longer period of time than without covalent binding
• no toxicity below a concentration of 150 μg/ml
• successful activation and maturation of dendritic cells by chitosannanocapsules with covalently bound PsaA antigen
• successful activation and differentiation of lymphocytes after presentation by dendritic cells
• triggering the release of TNFα and successful activation of CD4 and CD8 T-lymphocytes

Conclusion: The use of chitosannanocapsules is promising to achieve targeted activation of nasal immune cells. This is caused by an increased residence time in the nasal secretion due to a high mucoadhesion. Due to the covalent binding of PsaA to the chitosannanocapsule, a high loading of the antigen could be achieved. The loaded nanocapsules were shown to interact with immune cells and elicit a stronger response than the membrane proteins alone. Also, the high stability and maintenance of the properties of the nanocapsules during freeze-drying is promising for use as a vaccine. Last, by using the membrane protein PsaA, a serotype-independent vaccine can be generated. since the protein does not vary greatly between serotypes, unlike polysaccarides. Link to article: https://link.springer.com/article/10.1007%2Fs13346-021-00928-3