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Chitosan in an inhalable nanovaccine against SARS-CoV-2

The global corona pandemic requires effective vaccines to achieve herd immunity. In the study presented here, an inhalable chitosan-based nanovaccine containing the viral spike protein (S) was developed to specifically induce immunity at the mucosal sites of the respiratory tract.


Zhuo, SH., Wu, JJ., Zhao, L. et al. A chitosan-mediated inhalable nanovaccine against SARS-CoV-2. Nano Res. (2022).

SARS-CoV-2 has infected millions of people and caused many deaths since the pandemic began in late 2019. Especially due to the emergence of new mutations, it is urgent to achieve herd immunity to end the pandemic. Suitable vaccines are needed for this purpose.
The virus preferentially enters the human body via the respiratory tract, nose and mucous membranes through cell surface receptor angiotensin-converting enzyme 2 (ACE2) and viral spike protein (S). For the reason, mucosal immunity plays an important role for direct and effective protection against SARS-CoV-2. Recent findings showed that mucosal-related vaccines also elicited a strong IgA and IgG response. In addition, such vaccines, which could be administered as a nasal spray, for example, would have the advantage of not requiring needles and fewer medical personnel, as opposed to conventional vaccines, and could allow an easier handling.
Mucoadhesives are needed to make such a vaccine possible. Chitosan is a natural mucoadhesive that is suitable as an additive for many antigens due to its positive charge. It is also capable of temporarily opening tight junctions to allow easy penetration of drugs into the intercellular space.
Therefore, in the presented study, a pulmonary inhalable nanovaccine (S@CS) against SARS-CoV-2 was developed using the positively charged chitosan (CS) and the negatively charged spike protein S (S). For this purpose, CS and S were assembled into nanoparticles (NP) via physical mixing and electrostatic interaction. After verifying NP formation, the immunological effect and toxicity of the nanovaccine was investigated in vitro using bone marrow dendritic cells (BMDCs). Subsequently, immunity to the spike protein was tested in vivo in BALB/c mice.


  • Spherical morphology of nanoparticles with an average diameter of 210 nm
  • Change in zeta potential after physical mixing of S and CS→ Evidence of electrostatic interaction and NP formation
  • Significant increase in cytokines CXCL10, FN-β, IL-0, TFN-α in vitro (BMDC cells)
  • No evidence of cytotoxicity in vitro
  • In the presence of CS, there were 113.3 and 10.6-fold higher antigen titers of IgG in vivo compared with administration of S only and injection of S, respectively
  • In addition to ratio of 2.4 between IgG1 and IgG2a, the results induced humoral and moderate cellular immunity against SARS-CoV-2
  • Analysis of bronchoalveolar fluid via ELISA revealed that S@CS increased spike protein specific immune response and not free spike protein

Summary: In the presented study, a pulmonary inhalable nanovaccine composed of chitosan and spike protein S was developed against SARS-CoV-2. The chitosan-based vaccine was able to induce both humoral and cellular immunity. It also demonstrated comparable immunity to an injected vaccine. Therefore, an inhalable nanovaccine to induce mucosal immunity could provide an alternative to conventional vaccines. Link to article:


chitosan, nanoparticles, vaccine

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