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

participate in pathogen opsonization. However, most 
PRRs are transmembrane (like C-type lectin and Toll-
like receptors; CLRs and TLRs, respectively) or cytosolic 
(retinoic acid-inducible gene I and nucleotide-binding 
domain and leucine-rich repeat containing receptors; 
RLRs and NLRs, respectively). For the purposes of this 
review, we will discuss the uses of liposomes in vaccines 
that target CLRs and TLRs. The TLRs identified so far 
amount to 10 in humans, each one recognizing specific 
PAMPs from microbial pathogens (Table 
1
) [
10
–
12
]. TLR 
10 has been recently described as a modulatory recep-
tor; however, no known ligand has been linked to it [
13
]. 
Therefore, further research should be done on TLR 10 to 
uncover the ligand involved in innate immune responses.
Contrary to the transmembrane TLRs, CLRs are clas-
sified as soluble or membrane bound. Soluble CLRs (e.g. 
galectins and collectins) have been reviewed extensively 
[
9
, 
14
]. The mostly studied membrane-associated CLRs 
are DC-SIGN (DC-specific ICAM3-grabbing non-integ-
rin), Dectin-1 (dendritic cell-associated C-type lectin 1), 
Dectin-2 (dendritic cell-associated C-type lectin 2), MCL 
(macrophage C-type lectin) and MINCLE (macrophage-
inducible C-type lectin) receptors [
8
, 
9
]. These receptors 
play a significant role in immunomodulatory responses, 
triggering the differentiation of T-helper cells (T
H
cells) 
from naïve CD4
+
T cells, through the assistance of an 
APC. CLRs not only recognize PAMPs but also the dam-
aged-associated molecular patterns (DAMPs) and tumor-
associated molecular patterns (TAMPs) from the host 
[
15
] during the processes of apoptosis and tumorigenesis, 
respectively. Glycans from a myriad of pathogens (para-
sitic, fungal, bacterial or viral) are recognized by CLRs 
(Table 
2
); the most common being mannan [
16
], Man-
LAM (mannose lipoarabinomannan) [
17
], mycobacterial 
cord factor [
18
], β-1,3-glucans [
8
] and α-1,2-mannose [
8
, 
19
]. In humans, DC-SIGN recognizes both mannan and 
ManLAM; Dectin-1 recognizes β-1,3-glucans and Dec-
tin-2 recognizes α-1,2-mannose. In mice, mycobacterial 
cord factor is recognized by MINCLE and currently no 
glycans have been identified for the human MINCLE. We 
can observe from the literature review available, there 
is still more work to be done to determine ligands or 
PAMPs that interact with specific PRRs. Scientists must