Other delivery methods:

1. Liposome mediated:
Liposomes are formed when certain amphiphilic lipids self assemble in aqueous
buffer.
Liposome-based adjuvants may act as both delivery systems for subunit antigens
and as immunopotentiators.
They can be modified via: (i) the choice of lipid composition, (ii) the inclusion of
immunostimulating compounds, (iii) the choice of formulation method and
(iv) the mode of antigen and immunostimulator association

Image: By Kosi Gramatikoff w:user:kosigrim, Public Domain, https://commons.wikimedia.org/w/index.php?

curid=88999267
Classification of liposomes
1. Multilamellar vesicle (MLV, with several lamellar phase lipid bilayers)
2. Small unilamellar liposome vesicle (SUV, with one lipid bilayer),
3. Large unilamellar vesicle (LUV), and
4. Cochleate vesicle.
5. Multivesicular liposomes (one vesicle contains one or more smaller
vesicles).

Registered vaccines: hepatitis A (Epaxal) and influenza (Inflexal V)

Extra read:
1.Tandrup Schmidt, S., Foged, C., Korsholm, K. S., Rades, T., & Christensen, D. (2016). Liposome-Based Adjuvants for
Subunit Vaccines: Formulation Strategies for Subunit Antigens and Immunostimulators. Pharmaceutics, 8(1),
7. https://doi.org/10.3390/pharmaceutics8010007
2. https://doi.org/10.3389/fimmu.2018.00155
• Liposomes can be surface modified- add antibody , PEG
• Liposomes can contain drug/mRNA/DNA inside
• Liposomes can contain nucleic acid attached outside, in between lipids
Characteristics of different liposome mediated vaccine delivery
 How to form liposomes

1. Drying
2. Dispersal into
aqueous
3. Purification and
check

https://www.youtube.com/watch?v=vGz-qDE3Go4
 Phase transition temperature

Conditions that can be varied:

lipid composition, concentration, water content, different buffers ( varying ionic

strength, pH, etc); use of cholesterol ??
 Differences in liposomes – factors

1. Size of particle of liposomes

2. Surface charge
3. Surface modification?- stealth liposomes
4. How fluid is the layer ?
Incorporation of antigen/nucleic acid inside liposomes
Passive
Active

Advantages and disadvantages of liposomes

2. Immune stimulating complexes (ISCOMs):

•Spherical open cage-like structures (typically 40 nm in diameter) that are

spontaneously formed from cholesterol, phospholipids and Quillaja saponins under a
specific ratio (ISCOM matrix).
•The complex displays immune stimulating properties
•Works best for peptide
•Vaccine adjuvant- particularly T cells
•Can stimulate T cells
•Chemically stable, at 2-8°C, stable for a long time
•Long lasting effect

Extra reading:  
1. Morein, B; Sundquist, B; Höglund, S; Dalsgaard, K; Osterhaus, A (1984). "Iscom, a novel structure for antigenic
presentation of membrane proteins from enveloped viruses". Nature. 308 (5958): 457–60. Bibcode:
1984Natur.308..457M. doi:10.1038/308457a0. PMID 6709052.
2. Lövgren Bengtsson K, Morein B, Osterhaus AD. ISCOM technology-based Matrix M™ adjuvant: success in
future vaccines relies on formulation. Expert Rev Vaccines. 2011 Apr;10(4):401-3. doi: 10.1586/erv.11.25.
PMID: 21506635.
Image: https://www.creative-biolabs.com/vaccine/immune-stimulating-complexes-
iscoms.htm
3. Micro and Nanoparticles

Extensively tried, particularly with DNA vaccines

Most common polymer for DNA vaccine development is poly(lactide-co-glycolide)
poly(ethyleneimine) very successful as non-viral gene delivery vector; but DNA
complexes are toxic and aggregate in presence of serum proteins.

Natural polymers like chitosan used

What kind of materials?

Why use micro when you can use nano ?
Liposome , nanoparticles, microparticle, microspheres, microcapsules– The
myriad of confusing terms
4. Dendrimers: ( multiple antigen peptide approach (MAP))

Aimed at replacing a protein carrier in a peptide based vaccine, with a small structural unit
that can amplify peptide antigens without the disadvantages associated with protein carriers.

https://www.youtube.com/watch?v=zDj2rjeaHXE

Image: https://commons.wikimedia.org/wiki/File:Graphs.jpg
 Why dendrimers?
• Good for Encapsulation of hydrophobic compounds

• Properties: monodispersity, water solubility, encapsulation ability, and large number of

functionalizable peripheral groups
The framework of the dendrimer is a core matrix consisting of branching trifunctional
amino acids with the following properties: (i) non-immunogenic; (ii) ability to amplify
the peptide antigens into a macromolecule; (iii) flexibility to incorporate multiple
epitopes and (iv) accessible for chemical synthesis.
5. Cell penetrating peptides (CPP) or membrane translocating peptides (MTP):

Group of cationic peptides that have the ability to enter into the cytoplasm of cells. CPP
are able to deliver a number of antigens, including RNA, DNA, peptides, proteins, drugs
and virus particles into cells.

Read:
1. Xie, Jing et al. “Cell-Penetrating Peptides in Diagnosis and Treatment of Human
Diseases: From Preclinical Research to Clinical Application.” Frontiers in
pharmacology vol. 11 697. 20 May. 2020, doi:10.3389/fphar.2020.00697
2. Derakhshankhah H, Jafari S. Cell penetrating peptides: A concise review with emphasis
on biomedical applications. Biomed Pharmacother. 2018 Dec;108:1090-1096.
Antibodies as vaccine ?
 Human Immunome
https://www.immgen.org/
https://www.humanvaccinesproject.org/

Harvard Human Immunome

Why are some people protected from disease while others remain healthy?
Why do some people respond to cancer immunotherapy while others do not?
Why are some vaccines more effective for certain populations than others?
1000 Immunome project -Standford
 BTE 722 Vaccine technology
History of vaccine development- Importance of vaccines . Immunological response to vaccines
Vaccine safety-the debate.

Different types of vaccines: Inactivated toxins, Inactivated whole bacteria or viruses, Live
attenuated bacteria or viruses; Subunit vaccines, Polysaccharide vaccines, Conjugated vaccines ;
Recombinant DNA vaccines, Edible vaccines, Virus like particles; Next-generation vaccines:
Human Immunome project; Human antibodies as vaccines.

Vaccine design and development: Epitope identification; Adjuvants ; Delivery methods:

microspheres, nanoparticles; ISCOMS and immunomodulators.

Vaccine efficacy, Production techniques used for vaccines ; Storage and preservation of vaccines.

Regulatory issues in vaccine production: OIE guidelines for production and seed lot
management; Manufacturing recommendation; Final product release tests.