Table 3.

Comprehensive summary for the comparison of EV-protein vaccines and LNP-mRNA vaccines

Aspect	EV-Protein vaccines	LNP-mRNA vaccines
Advantages
Immune response	Superior immunogenicity with both humoral and cell-mediated responses	Limited ability to induce mucosal immunity, primarily systemic
Storage and distribution	Efficient global manufacturing and accessibility	Ultra-cold storage requirements pose distribution challenges
Protein loading	Accommodates transmembrane glycoproteins for effective antigen display	Limited to purified synthetic or soluble recombinant proteins
Safety	Inherent safety, no documented significant toxicity	Inherent toxicity associated with LNPs, leading to adverse effects
Scalable mManufacturing	Large-scale, continuous manufacturing process	Non-continuous, complex, and expensive manufacturing process
Stability	Could be lyophilized. No need for cold chain logistics	Ultra-cold storage requirements. Required cold chain logistics
Antigen presentation	Direct antigen presentation	Required additional step of translation for presentation
Mucosal immunity	Potential to stimulate both mucosal and systemic responses	Primarily induces systemic immunity, weak in mucosal immunity
Rapid response to emerging pathogens	Yes	Yes
Disadvantages
Heterogeneity	EVs are a heterogeneous population; achieving consistency may be challenging	LNPs are chemically constituted and are more precisely defined
Targeting precision	EV targeting is not well defined	LNPs designed for specific targeting may have higher targeting precision
Stability in biological fluids	EVs are subjected to the same degradation and clearance as most biologicals in biological fluids	LNPs as synthetics could be engineered to overcome biological degradation
Biological barriers	EVs may face challenges in crossing tissue barriers and escaping lysosomal degradation	LNPs may also encounter biological barriers, influencing efficacy