Table 2.

Advantages and Disadvantages of different vaccine technologies in mucosal vaccination.

Antigen Delivery	Advantage	Disadvantage	References
mRNA	Synthetic, non-infectious, and free from cellular or egg proteins.	Sensitive to pH and degradation by enzymes.	[71,123,124]
	Short development and manufacturing time.	Inability to penetrate mucus barriers.
	Produces high systemic antibody titers.	Adjuvants are required to break mucosal immune tolerance.
	Transient expression.	Poor mucosal immune response.
	Cannot modify host genome.	Ultra-low cold chain required for storage.
Protein Subunit	Can be lyophilized for good environmental stability.	High antigen requirement.	[71,123]
	Can be used regardless of age or immunocompromised status	Sensitive to pH and degradation by enzymes.
	Cannot modify host genome.	Inability to penetrate mucus barriers.
		Adjuvants are required to break mucosal immune tolerance.
		Poor mucosal immune response.
		Complex manufacturing requirements (conjugation chemistry).
		Difficult to isolate the most relevant antigens.
Live Viral	Well-established technology. Better stability than mRNA vaccines.	Complex manufacturing and safety requirements.	[71,123,125]
	Naturally capable of penetrating mucus barriers, tolerating high/low pH, and infecting target cells.	Cannot be given to immunocompromised patients.
	Induces strong mucosal and systemic immune responses.	Small chance of reverting to a pathogenic form and causing disease.
	May not need adjuvants	Takes time to develop.
	Simple to manufacture.
Viral Vector	Induces strong mucosal and systemic immune responses.	Concerns for host genome modification/integration.	[71,123,126]
	Naturally capable of penetrating mucus barriers, tolerating high/low pH, and infecting target cells.	Complex manufacturing and safety requirements.
	May not need adjuvants. Better stability than mRNA vaccines.	Response reduced due to pre-existing immunity against the vector.
	Simple to manufacture.	Takes time to develop.
	Cannot cause diseases like live attenuated viruses.