Liposomal vaccine formulations as prophylactic agents: design considerations for modern vaccines

Liposome design
When designing liposomal vaccines, we should take into 
consideration certain factors within the liposome struc-
ture and its physicochemical properties (Fig. 
1
). Previ-
ous reviews on the topic have discussed the different 
parameters that could affect the functions and efficacy of 
liposomes as vaccine agents [
23
, 
24
]. Liposomal subunit 
vaccines are safe, with low reactogenicity, biodegradable 
and versatile. Reactogenicity refers to the low incidence 
of expected immune responses, causing symptoms like 
allergies, fever or pain at injection site among others. 
This type of vaccine contains antigen(s) (either a protein, 
lipid, lipopeptide etc.) from the pathogen of interest that 
is incorporated (depending on the antigen physicochemi-
cal nature) in the lipid bilayer or core of the liposome. 
The liposome will serve as an adjuvant, which potentiates 
the immune responses of the vaccine, improving its effi-
cacy. Antigen incorporation can be achieved by covalent 
lipid conjugation (at pre- or post-vesicle formation), non-
covalent surface attachment (by antibody–epitopes inter-
actions), encapsulation, electrostatic interactions (with 
lipids of opposite charge) or surface adsorption. Seminal 
articles published earlier covered the effects of antigen 
encapsulation or adsorption on innate immune response 
differentiation [
25
–
27
]. Researchers reported that both 
incorporation methods dichotomously induced immune 
responses that enhanced T cell differentiation, when 
albumin was used as the incorporated model antigen in 
the liposomal formulations. However, when antigen size 
and complexity decreases (like in virus- or tumor-derived 
antigens), a surface adsorption incorporation method 
will induce better immune responses than encapsulation 
[
28
, 
29
].