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

Immunostimulatory lipids and liposome deposition
Immunostimulatory lipids might be of value in the vac-
cine design process. The lipids can act as adjuvants in the 
vaccine formulation and enhance the immune response 
we are looking for (innate or adaptive) as previously 
reported and reviewed [
2
, 
5
, 
6
, 
47
]. In a study developed 
by Rao et al., two adjuvants (lipid A and CpG-contain-
ing oligodeoxynucleotides, CpG-ODN) were studied 
in a liposomal formulation based on the HIV envelop 
protein ogp140 [
55
]. Both lipid A and CpG-ODN-con-
taining liposomes elicited six and threefold anti-ogp140 
antibodies, respectively. Immunization of BALBc mice 
with the HIV antigen incorporated in lipid A-containing 
liposomes produced a mixed T
H
1/T
H
2 immune response. 
Combining both adjuvants in the liposomal formulation 
generated a T
H
1 immune response. Puangpetch et al. 
presented the effect of using zwitterionic or cationic 
lipids in vaccine liposomal formulations [
2
]. Research-
ers compared DOTAP (cationic phospholipid) vs. DOPC 
(neutral phospholid) containing the adjuvant CpG-ODN. 
DOTAP-based liposomes with adjuvant enhanced the 
immune response against Burkholderia pseudomallei, 
which suggest an alternative approach for the treatment 
of melioidosis. The published data available suggests that 
certain lipids can induce, or enhance, immune responses. 
Very important is the fact that cationic liposomes are 
the ideal model to design effective vaccines due to their 
immunostimulatory properties.
Finally, the immunostimulation of the vaccine can be 
affected by the deposition of liposomes at the site of 
injection which in turn is affected by particle size. Hen-
riksen-Lacey et al. reported this in two separate articles 
[
6
, 
56
]. On Henriksen-Lacey et al. researchers utilized 
the phospholipid DDA as the building block for the 
liposomes containing the adjuvant TDB. The antigen for 
tuberculosis infection, Ag85B-ESAT-6, was co-admin-
istered or incorporated to liposomes in mice. Antigen 
administered alone to mice did not created a depot 
at the site of injection, causing the antigen to diffuse 
away from the site and reduce immune responses. The 
observations directed them to conclude that cationic 
liposomes made up of DDA promotes depot formation 
at the site of injection mainly due to size characteristics 
between antigen-loaded liposomes and antigen admin-
istered alone. Later, Henriksen-Lacey et al. [
30
] stud-
ied the effect of liposome composition [DOTAP, DDA 
or DC-Chol (dimethylaminoethane-carbamoyl-choles-
terol)] and the depot formation and antigen distribu-
tion. DDA and DC-Chol represented the phospholipids 
where liposomes induced the migration of monocytes to 
the site of injection and a significant increase of IFN-γ 
levels. In general, larger liposomes will form a depot at 
the site of injection meanwhile smaller liposomes will 
migrate to lymphoid tissue for antigen presentation and 
processing.

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De Serrano and Burkhart  J Nanobiotechnol (2017) 15:83