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

Surface charge
The surface charge of liposomes would be of impor-
tant consideration for appropriate vaccine design. The 
overall charge can determine the adsorption or antigen 
interaction with the liposomes (e.g. anionic antigens 
will prefer to interact with cationic lipids) which affects 
antigen loading in the vaccine [
18
]. Hussain et al. found 
that replacing the cationic lipid DDA with the neutral 
lipid distearoyl-sn-glycero-3-phosphocholine (DSPC) 
decreases the amount of the tuberculosis recombinant 
antigen H56 from 84 down to 15%. In addition, the func-
tion of the vaccine in relation to immune response induc-
tion is well documented. Joseph et al. were studying an 
intranasal influenza vaccine model based on the lipo-
somal formulation of the HN antigen with the polyca-
tionic sphingolipid ceramide carbamoyl-spermine (CCS) 
or other monocationic, neutral and anionic lipids [
45
]. 
Neutral and anionic lipid-based formulations were not 
immunogenic upon intranasal administration in a murine 
model. However, two out of five monoccationic-based 
liposomal formulations (containing lipids 1,2-dimyris-
toyl-3-trimethylammonium-propane, DMTAP; and 
1,2-dioleoyl-3-trimethylammonium-propane, DOTAP) 
induced vigorous local and systemic immune responses 
(T
H
1 and T
H
2 type responses). Researchers compared 
the monocationic liposomal formulations with the 
CCS-based liposomal formulation and the only com-
mercially available influenza vaccine, demonstrating 
the efficacy of the sphingolipid as an immunopotentia-
tor with higher antibody titers and protective immunity 
for approximately 9 months. Another study with New-
castle disease virus compared the immunization effects 
in chickens of neutrally- (EPC-Lip), anionically- (PS-
Lip) and cationically-charged (SA-Lip) liposomes [
46
]. 
Strong humoral responses (local and systemic) were 
observed in neutral formulations of EPC-Lip, contrasting 
to the cationic SA-Lip. The anionic formulation mainly 
composed of phosphatidyl serine (PS-Lip) elicited the 
higher hemagglutination titers. Recently, Hussain et al. 
determined that replacing the cationic lipid DDA with 
the neutral DSPC reduced the T
H
1-mediated immune 
response of the formulation [
18
]. Based on the studies 
presented above we can conclude that cationic formula-
tions might be the most suitable option to elicit strong 
immune responses, increasing antibody titers. There is 
additional information available about cationic lipids, like 
DDA, which possess significant immunostimulatory and 
adjuvanting properties [
47
, 
48
] and further explanations 
will be provided ahead.