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

Table 1 Pathogen-associated molecular patters (PAMPs) recognized by specific TLRs
ds double stranded, ss single stranded
Pathogen-associated molecular pattern (PAMP)
Microorganism or classification
TLRs
Lipoproteins
Bacteria
TLR 1
Peptidoglycan and lipoteichoic acid
Gram positive bacteria
TLR 2
β-glucans
Fungi
dsRNA
Double-stranded and negative-stranded viruses
TLR 3
Lipopolysacharide (LPS)
Gram negative bacteria
TLR 4
Flagelin
Bacteria
TLR 5
Profilin
Toxoplasma gondii
Lipoproteins
Mycoplasma
TLR 6
Imidazoquinolines and ssRNA
Single-stranded viruses
TLR 7 and 8
Unmethylated CpG DNA motifs
Prokaryotic genomes and viral DNA
TLR 9

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De Serrano and Burkhart  J Nanobiotechnol (2017) 15:83 
pay close attention to interspecies differences in PAMP 
recognition by PRRs, since we can obtain unwanted 
immune responses once we study them at the human 
level. Unwanted immunomodulatory responses can com-
promise the patient’s outcome from the disease.
In the vaccine development field, we can identify the 
importance of collaboration between medicinal chem-
istry, immunology and formulation science. This arti-
cle will present and discuss several parameters that 
play prominent roles in liposomal vaccine develop-
ment. Liposome size, charge and bilayer composition 
are some of those parameters to be discussed. Evidence 
will be presented to the reader for understanding of 
the mechanisms or effects of such liposome physico-
chemical characteristics, which impact vaccine devel-
opment, safety, integrity and efficacy. Furthermore, 
we present different applications of liposomal vaccine 
studies that have been published for the treatment of 
certain infections of distinct etiological origins (viral, 
bacterial, fungal and parasitic). Finally, the article pre-
sents a special section on the development of subu-
nit cationic liposomal vaccines for the prophylactic 
treatment of tuberculosis infections, one of the most 
sought-after indications in contemporary vaccinol-
ogy. The section for tuberculosis vaccine development 
is focused on DDA-based liposomes; and additional 
information is available that presents other lipids or 
phospholipids [
20
, 
21
]. The manuscript objective is to 
present liposomal formulations that are not currently 
commercially available and inform the scientific com-
munity about liposomal formulation for early vaccine 
development. To date, there are only two commercially 
approved liposomal vaccines Epaxal and Inflexal, both 
by Crucell/Berna Biotech. We recommend the reader 
to further their knowledge in commercially available 
liposome-based vaccines with another review [
22
], 
which discusses the topic extensively.