Importance of Vaccines and how the 9/11 change the face of vaccine field. A glimpse of world/Indian vaccine industry

1. “Life or death for a young child too
often depends on whether he is born
in a country where vaccines are
available or not”

2. accines: All the things considered

3. The Spanish FLU
1918-1919 more than 50million people

4. G
O
O
D

5.  ARI
 HIV
 Diarrhoeal diseases
 Tuberculosis
 Malaria
 Measles, Hepatitis B virus
The infectious diseases

6. The World Health Organisation

7.  Vaccination is probably the most beneficial
therapy that a physician can provide a patient
 Vaccines are an excellent, technically feasible
defense against these threats with the potential
to limit disease spread
Prevention is better than cure

8. Success stories of vaccines
 Small pox
 Polio, by 99.9% from 3,50,000 cases in
1998 to 800 in 2002
 39% decrease in mortality because of Measles
 End of 2003 78% of world population got
immunized with DTP

9. Biological basis for immune
response to a vaccine ?

10. Late 20th
Century T cell
21st
Century Dendritic Cell
Controller of immune response
Dendritic cell
T cell

11. “Unfortunately the DC biology is still very confusing”“Unfortunately the DC biology is still very confusing”
Immature DC
Pathogens
DC
Cytokines
APC
APC T-Cell Cytokines Activated Cells

12. Conserved microbial molecules shared by many pathogens
 Bacterial lipopolysaccharides – TLR4
 Peptidoglycan – TLR2
 Flagellin – TLR5
 Nucleic acids
Pathogen-associated molecular patterns (PAMPS)
Pattern Recognition Receptors
(PRR) Toll like receptors

13. Toll-like receptors & Host-Pathogen Interaction

14. What decides Th1 or Th2 response ?
IL-12, IFN-γ, Controll Intra cellular pathogens
Combination of both antibody and CMI
Th1
Th2 Predominantly antibody response
Th1 Th2
Antagonistic

15. Need to look for new adjuvants
 What is the role of adjuvants ?
 Alum based adjuvants are only approved and
Problem with Alum ?
 IL-12 cytokines and antigen loaded dendritic cells
as adjuvants are in pipeline

16.  MPL (monophosphoryl lipid A)
 Montanide ISA51 (seppic)
 MF59
 Mix of different adjuvants (Alum+MPL) also used
in few vaccines ex. Human papillomavirus ,
Herplex simplex virus (GlaxoSmithkline)
 LEAPS (Ligand epitope antigen presentation system)
 ICBL (Immune cell binding ligands)
Newer adjuvants
Problems with small peptide vaccines

17. Reason for these Studies
 Increased understanding of the immune response
 Technology advances in
Proteomics
Genomics
Structural biology
Instrumentation
New developments in vaccine designNew developments in vaccine design

18. Hurdles to the development and
licensing of new vaccines

19.  Difficulty in preparing 100% safe and effective
 Almost unavoidable minor adverse event
 The high cost of testing
 Long time to get through phase III trials
 Profit margin is 1/10 or less than that of a successful drug
that must be taken daily
 Target for lawsuits
Hurdles…Contd.

20. Beyond that
 Vaccine program's are expensive
 Vaccines are perishable
 Administration by professionals
 People may not accept without a defined urgent
microbial threat

21. Produce an immune response ?
Protect after challenge?
Safe ?
Immune response ?
Best dose?
Safe ?
How much of an
immune response ?
Does it work ?
Preclinical Phase I Phase II Phase III
Animals
30-50 people
200-400 people
3000-5000 people
Goals of vaccine Trial process

22.  Fails if it is effective only in a subgroup
of patients or if a subgroup experiences
extreme side effects
Failure on the way to success
 Variable outcomes caused by the particular
genetic makeup of the individuals
ex. Worlds first AIDS vaccine AIDSVAX

23. ex. In 2000 Rotashield® vaccine was withdrawn from the
US market due to safety concerns
Risk benefit ratio must be reasonable
 Vaccines also have some undesired side effects
 A safety evaluation must ask not only “what are the
bad
things that can happen if this vaccine is used?”
 It must also ask, “what bad things can happen if this
vaccine is NOT used?”

24. Bitter truth
 Clinically not proven in preventing disease
 Simple reason that no researcher has directly
exposed test subjects to diseases
 Go to doctor and you get a toxic additive than
the viral component
ex. Thimerosal - Autism
BSA - Prion diseases

25. Drive for Vaccine development
Benefit to mankind
Profit

26. The big Three vs neglected diseases
 HIV
 Malaria
 TB
 Hookworm disease
 Schistosomiasis

27. Money
Time
Success
Profit
Worries with vaccines
231million $ in 1987 to 802 million$ in 2000
Vaccine is expensive to develop,
licensure, and marketing
As a result funds are always from Government

28. Drive for vaccine funding by Government
Fear : Fear of Bioterrorism
Fear of being blamed for inaction
Concern over lost revenue due to illness
“Fear of bioterrorism elevates infectious diseases to the
status of a military weapon and changes the definition
of vaccine program in to military deterrent”
“Fear of bioterrorism elevates infectious diseases to the
status of a military weapon and changes the definition
of vaccine program in to military deterrent”

29. Bioterrorism
Boom in the Vaccine development

30. Project Bioshield
Goals of Project Bioshield
 Accelerate the R & D on vaccines
 Purchase
 Availability of priority medical
countermeasures to protect the US
population

31. Change in Vaccine industry after Bioshield
Contracts since 2001 to pileup
 80 million doses of Anthrax vaccine
 Botulin antitoxin
 Smallpox vaccine
 Plague
 Ebola fever
“Change the future of vaccine development”“Change the future of vaccine development”

32. To improve child health in poorest countries
GAVI ALLIANCE

33. Innovative partnership for benefit of mankind

34. Bill and Melinda Gates foundation
The largest transparently operated charitable foundation
in the world
 Malaria Vac I
 Childrens Vac I
 HIV

35. WARREN BUFFET

36. Global vaccine industry
US$ 11.42 Billion in 2006
US$ 21.05 Billion by 2010
After decades of malaise vaccine industry is getting injection
But remains small piece 3% of drug industry

37. 24.3
22.6
21.3
17.8
8.1
5.9
•Novartis/
•Chiron*
•GSK
•Wyeth
•Merck**
•Sanofi-
Aventis**
•Other
Growing market with a restricted number of
mostly US-prone vaccine players

38. Vaccine industry in India
 Shanta is first to indigenously produce a rec
Hep B vaccine
 Shantha and Serum institute are working
on pentavalent vaccine ( DPT, HepB, influ B)
 Bharath biotech working on malaria &
rotavirus (Bill & melinda)

39. Contd…
 Indian immunologicals
 Biological E
 Panacea biotech
 Serum Institute of India
 Shanta supplies 40% of UNICEF global
requirement for Hep B
 Serum institute highest exporter-138
countries
Surprising facts

40. Summary
 More R&D on immunology and host pathogen interaction
is required
 Government can enrich the funding for vaccine R&D
 NIH remains primary funding source
for most vaccine projects
 Database of NIH for past 10 years
indicate more funding for pharmacy
3%
17.5%
NIH

41. Vaccine research shouldn’t stop there

42. Thank you
“ We cannot be a strong nation unless we are a
healthy nation“