1. Course Contents An introduction to Vaccinology
Vaccine history and types
Epidemiologic basis of Vaccinology
Role of combination vs. single vaccines
The immune responses to the pathogen & vaccine development
Immunology of Vaccines
Antigen and Vaccine Delivery Strategies
Determinants of Vaccine Availability
Vaccine development strategies: New approaches
Live versus attenuated vaccines
Role of multinational companies in vaccines production
DNA as vaccine
Peptide & Subunits vaccine
Adjuvants in vaccines
Population Genetic analysis: immunity to vaccine
Recombinant vaccine
Animal models of vaccine testing
Vaccine Delivery Systems
Practical issues in relation to trials
Ethical issues related to clinical evaluation of vaccines
Vaccine safety
Review of vaccines in current use
Vaccine-economics
Future of Vaccines/Vaccination

2. Course Contents PART 1 : INTRODUCTION Definition History Types
Combination vs single vaccine
Part 2: Principles of Vaccine Design
Immunologic Memory: T and B Cells memory
Antigen Processing and Presentation by MHC Class I, II, and Nonclassical Molecules
Understanding the Mucosal Immune System for Better Mucosal Vaccine Design
Part 3: ANIMAL MODELS FOR VACCNE TESTING
Utility of Mouse Models in Vaccine Design and Development,
Utility of Nonhuman Primate Models for Vaccines,

3. Part 4: Delivery Systems
Transcutaneous Immunization via Vaccine Patch Delivery System
Needle-free Jet Injection for Vaccine Administration
Oral Vaccines: An Old Need and Some New Possibilities Adjuvants:
PART 7: Population genetics and vaccines
Ethical issues
Vaccine safety
Part 6: Regulatory Considerations
Regulatory Issues
Role of international companies
Vaccine economics
Part 5: Evaluating Vaccine Efficacy
Trials in human and practical issues

4. VACCINE DELIVERY SYSTEMS

5. VACCINE DELIVERY SYSTEMS
1. VIRAL VECTORS BASED
2. NON VIRAL

6. VACCINE DELIVERY SYSTEMS
MUCOSAL DELIVERY OF VACCINES
LIPOSOMAL DELIVERY SYSTEMS
VIROSOMES DELIVERY SYSTEMS
POLIMERIC NANOPARTICLE DELIVERY SYSTEMS
DENDRIMER-BASED DELIVERY SYSTEMS
NEEDLE-FREE DELIVERY
EDIBLE VACCINES
DNA VACCINES:

12. Nanopatch
A stamp-size patch similar to an adhesive bandage contains about 20,000 microscopic projections per square inch. 
When worn on the skin, it will deliver vaccine directly to the skin, which has a higher concentration of immune cells than the muscle tissue does, which is one of the tissues where injections commonly deliver vaccines.

14. Dermal administration by nanopatches thus increases the effectiveness of vaccination,
requiring less vaccine than injection.

22. LIPOSOMAL DELIVERY SYSTEMS

23. Liposomes and their derivatives “lipoplexes” (liposome/DNA complexes) are hollow spherical constructs of phospholipid bilayers capable of entrapping hydrophilic moieties in the aqueous compartment and hydrophobic moieties in the lipid bilayers with cholesterol imparting rigidity to the bilayer.
Viruses, proteins, glycoproteins, nucleic acids, carbohydrates, and lipids can be entrapped and targeted at cellular and subcellular level for evoking immune responses
Diphtheria liposomal vaccine shows good immunogenicity and tolerance in humans

24. VIROSOMES DELIVERY SYSTEMS
Virosomes represent vesicular systems into which antigens can be loaded into virosomes or adsorbed onto the virosomal surface through hydrophobic interactions

25. VIROSOMES DELIVERY SYSTEMS
Virosomes are small spherical unilamellar lipid membranes of nucleocapsid including vesicles (150 nm) embedded with viral membrane proteins such as hemagglutin and neuraminidase of influenza virus but devoid the genetic material of the source virus.
Once they have delivered the antigens, the virosomes are completely degraded within the cells

27. DENDRIMER-BASED DELIVERYSYSTEMS
Dendrimers are branched, synthetic polymers with layered Architectures. to bind the DNA and get it into the cell.

28. DENDRIMER-BASED DELIVERYSYSTEMS
Dendrimers, available under the trademark name of “Starburst” serve as nonviral gene transfer agents, enhancing the transfection of DNA by endocytosis and, ultimately, into the cell nucleus.
A novel approach for the treatment of renal cell carcinomas uses a chimeric molecule comprising a granulocyte macrophage colony stimulating factor (GM-CSF) attached to a G250 kidney cancer specific antigen which is transfected in to the cancerous cell by the use of dendrimer

29. POLIMERIC NANOPARTICLE DELIVERY
SYSTEMS
Polymeric nanoparticles because of their size are preferentially taken up by the mucosa associated lymphoid tissue. They are extensively reviewed for nasal and oral delivery of vaccines

30. EDIBLE VACCINES

31. CONCLUSION
Vaccine drug delivery systems are gaining popularity these days due to the benefits they offer.
As they avoid the need to administer booster doses and provide a long term therapy in small dose.
Needle free technologies, Edible vaccines on the other hand open an attractive avenue for the oral delivery of vaccines.

33. VECTORS IN VACCINE DELIVERY
To transfer the desired
gene into a target cell,
a carrier is required.
Such vehicles of gene
delivery are known
as vectors.
2 main classes
Viral vectors
Non viral vectors

36. Cancer Vaccines CD4 T Cell Activated Dendritic TCR Cell Class II MHC
Cytokines = HELP
CD8 T Cell
Activated CD8 T Cells Traffic to Tumor and Lysis Cells
Burch et al, 2000; Small et al 2000; Fong et al, 1997.
Class II MHC
TCR
Figure 2. T cell and dendritic cell interaction in draining lymph nodes.
Tumor Antigen
Class I MHC

37. Viral Vaccines – Same Idea: But Starting At A Different Step
PSA
LFA-3
ICAM-1
B7-1
Co-Stimulatory Molecules
Target Antigen
Plasmid DNA
Vaccinia Virus
Fowlpox Virus
rV-PSA-TRICOM
rF-PSA-TRICOM
Packaging Cell Line
Vaccine
ProstVac VF
PSA= prostate-specific antigen.
Madan et al, 2009; Sonpavde et al, 2011; Drake, 2010.

38. ProstVac VF CD4 T Cell TCR Class II MHC Class I MHC Epithelial Cells
ACTIVATED
Madan et al, 2009; Sonpavde et al, 2011.
Figure 2. T cell and dendritic cell interaction in draining lymph nodes.

39. he antigen prostatic acid phosphatase (PAP), which is present in 95% of prostate cancer cells, and
an immune signaling factor granulocyte-macrophage colony stimulating factor (GM-CSF) that helps the APCs to mature.
The only cell-based therapy currently approved for the treatment of prostate cancer.

41. APPLICATIONS
Basic research
Gene therapy
vaccines

43. MOST COMMON VIRAL VECTORS
Retroviruses
can create double-stranded DNA copies of their RNA genomes. Can integrate into genome. HIV, MuLV, Rous sarcoma virus
dsDNA viruses that cause respiratory, intestinal, and eye infections in humans. Virus for common cold
ssDNA viruses that can insert their genetic material
at a specific site on chromosome 19
dsDNA viruses that infect a neurons. Cold sores virus
Adenoviruses
Adeno-associated viruses
Herpes simplex viruses

46. ADENOVIRUSES
As opposed to Lentiviruses, adenoviral DNA does not integrate into the genome and is not replicated during cell division.
with adenoviruses, which cause respiratory, gastrointestinal and eye infections, they trigger a rapid immune response with potentially dangerous consequences. To overcome this problem scientists are currently investigating adenovirusesto which humans do not have immunity.

48. their basic biology has been studied extensively
the viral genome can accommodate large heterologous transgene insertions,
they readily infect quiescent and dividing cells,
they can be amplified to high titers and
they have previously been shown to be relatively safe for use in humans.

50. ADENO-ASSOCIATED VIRUSES
AAV is not currently known to cause disease and consequently the virus causes a very mild immune response. AAV can infect both dividing and non-dividing cells and may incorporate its genome into that of the host cell. These features make AAV a very attractive candidate for creating viral vectors for gene therapy

52. HERPEX SIMPLEX VIRUS VECTOR

54. VIRAL VECTORS 1) RETROVIRUS VECTOR SYSTEM
The recombinant retroviruses  have the ability to integrate into the host genome in a stable fashion.
Can carry a DNA of
size – less than 3.4kb
Target cell - dividing

55. Retroviruses
number of FDA-approved clinical trials such as the SCID-X1 trial.
either be replication-competent or replication-defective..
involves the requirement for cells to be actively dividing for transduction.
cells such as neurons are very resistant to infection and transduction by retroviruses.
There is concern that insertional mutagenesis due to integration into the host genome might lead to cancer or leukemia

56. Retro virus

60. A PRACTICAL EXAMPLE OF RETROVIRAL VECTOR
VIRAL VECTOR xlox(NGFR)TERT AG
LNGFR
GP2-293
GP2xTERT11 PRODUCER CELL LINE
ENVELOPE CONSTRUCT
PRIMARY T CELLS
PACKAGED TERT RECOMBINANT VECTOR N S
Staining with anti-NGFR ab beads
A PRACTICAL EXAMPLE OF RETROVIRAL VECTOR