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

Liposome-immune cell interactions to improve 
vaccine effectiveness
Early vaccination strategies included the development of 
attenuated or inactivated vaccines, which are composed 
mainly of weakened or dead pathogens, respectively. 
Currently these kinds of vaccines are facing challenges 
with variabilities in immune response induction [
57
, 
58
]. 
Modern vaccination strategies are emphasizing the study 
of subunit vaccines and proving their effectiveness in 
immune response modulation [
59
, 
60
]. Subunit vaccines 
are characterized by the co-delivery of adjuvants and 
antigens for immunostimulatory purposes (Fig. 
2
). The 
antigen is either a natural or recombinant peptide, pro-
tein or molecule derived from the pathogen. The adju-
vant will enhance the immune response of the vaccine 
and potentiate the effect of the antigen during the pro-
cess. It is very important to know how to present the anti-
gen incorporated in the liposomes to APCs because this 
will ensure their proper immune cell maturation, antigen 
presentation and eventual induction of adaptive immune 
responses as previously reviewed [
61
, 
62
]. Cell target-
ing studies have been investigated and produced signifi-
cant data and observations of how antigen presentation 
plays a significant role. Aramaki et al. investigated the 
utilization of liposomes as carriers for antigens related 
to gut-associated lymphoid tissue and their uptake by rat 
Peyer’s patches [
63
]. Preferential uptake was observed 
for liposomes in the rat Peyer’s patches than non-patch 
tissues, specifically for DSPC:PS:Chol liposomes. This 
suggests that liposome composition affects their uptake. 
Fluorescently labeled liposomes were internalized by 
patch tissue in the lower ileum with size (> 374 nm) play-
ing an important direct correlation with uptake. Another 
report looked at how cationic vesicles composed of DDA 
could interact with normal and transformed mouse fibro-
blasts cells [
64
]. Cell–cell adhesion was observed when 
DDA concentration was equal or greater to 50 µM. Inves-
tigators determined that normal cells were susceptible for 
DDA vesicles meanwhile transformed cells were resistant 
to DDA-mediated (> 1 mM) cell death. The interaction 
with cationic vesicles created a change in cell charge from 
anionic to cationic, making this system of cationic vesi-
cles ideal for the delivery of negatively charged macro-
molecules like proteins and DNA.