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

Conclusion
Vaccination represents the major advancement of modern 
medicine, second in effect only to clean water, in decreas-
ing the spread of detrimental diseases and providing better 
quality of life. To develop effective and safe vaccines, col-
laboration between immunologists and formulation sci-
entists must exist. This collaboration will ensure that the 
vaccine is designed adequately and that the therapy will not 
cause unwanted immune responses. Also, it is important 
to understand the basic concepts in immunology (innate 
vs. adaptive immunity) so we can target the correspond-
ing receptors with the ligands and antigens employed in the 
vaccine. Many types of cell receptors participate in PAMPs 
recognition (innate immunity), namely NLRs, STING, 
RLRs, TLRs and CLRs. Each receptor contributes to signifi-
cant responses that lead to T helper cell activation and dif-
ferentiation, with eventual B cell (antibody-mediated) and 
CD8 T cell-mediated adaptive immune responses.
For liposomal vaccines, we must pay close attention 
to liposome size, surface charge (ζ potential), morphol-
ogy (lamellarity) and lipid bilayer fluidity. Size may affect 
antigen presentation to APCs and consequently immune 
responses. Likewise, surface charge of the liposome may 
affect antigen adsorption on the liposome and could 
affect liposome-cell interactions (cationic liposomes 
interact better with the anionic membrane of immune 
cells). MLVs may reduce antigen presentation due to their 
concentric vesicle morphological nature, contrasting to 
ULVs which enhances antigen presentation. Antigen leak-
age and immune response reduction may occur on how 
the antigen was formulated (adsorption vs. absorption). 
Absortion is explained by the T
m
of the lipids or phos-
pholipids used when developing the vaccine. Lipids with 

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De Serrano and Burkhart  J Nanobiotechnol (2017) 15:83 
lower T
m
tend to be fluid meanwhile lipids with higher 
T
m
would increase bilayer rigidity. During adsorption, 
the antigen is exposed in the outer layer of the lipid mem-
brane, which could allow easy release or presentation of 
the antigen. Additionally, we must pay special attention 
to how liposomes would interact with immune cells and 
how we can target those cells, enhancing proper immune 
responses. Adjuvants play a significant role in APCs acti-
vation and maturation for eventual T and B cell activation. 
The adjuvants, properly selected, will interact with their 
corresponding TLRs or CLRs in a process called targeted 
cell vaccine delivery. This cell targeted process is also 
affected by the vaccine route of administration.
We observed in the sections previously discussed key 
developments in contemporary vaccine research for the 
treatment of viral, bacterial, fungal and parasitic infections. 
The studies presented to the reader demonstrated the col-
laborative and interdisciplinary nature of the field. Cell tar-
geting and adjuvants dominated most of the approaches 
to develop effective prophylactic subunit vaccines for the 
treatment of detrimental diseases. In some instances, 
infection was hindered by the antimicrobial, antiviral, 
antifungal or antiparasitic activities of the vaccines due to 
the induction of adequate immune responses (cell- and 
antibody-mediated), leading to the survival of selected ani-
mal models. Additionally, we can conclude that cationic 
liposomal vaccines are of great interest for future vaccine 
development due to their enhanced interaction with the 
negatively charged immune cells. In specific, DDA-based 
liposomes are being tested in diverse vaccine studies which 
promise significant advances in the field. Such DDA appli-
cations as a building block of liposomal vaccines represent a 
step forward towards the prophylactic treatment of diverse 
infections. These developments will improve the current 
vaccine approaches and will provide better treatments for 
patients. Additional research efforts must be made towards 
the development of novel adjuvants that will contribute 
to the induction of significant immune responses. Both 
authors read and approved the final manunscript.