vaccines: all things considered
DESCRIPTION
Importance of Vaccines and how the 9/11 change the face of vaccine field. A glimpse of world/Indian vaccine industryTRANSCRIPT
“Life or death for a young child too often depends on whether he is born in a country where vaccines are available or not”
Vaccines: All the things considered
The Spanish FLU
1918-1919 more than 50million people
GO
OD
ARI
HIV
Diarrhoeal diseases
Tuberculosis
Malaria
Measles, Hepatitis B virus
The infectious diseases
The World Health Organisation
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
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
Biological basis for immune response to a vaccine ?
Late 20th Century T cell
21st Century Dendritic Cell
Controller of immune response
Dendritic cell
T cell
“Unfortunately the DC biology is still very confusing”“Unfortunately the DC biology is still very confusing”
Immature DC Pathogens
DCCytokines
APC
APC T-Cell Cytokines Activated Cells
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
Toll-like receptors & Host-Pathogen Interaction
What decides Th1 or Th2 response ?
IL-12, IFN-Controll Intra cellular pathogens
Combination of both antibody and CMI
Th1
Th2 Predominantly antibody response
Th1 Th2 Antagonistic
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
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
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
Hurdles to the development and licensing of new vaccines
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.
Beyond that
Vaccine program's are expensive
Vaccines are perishable
Administration by professionals
People may not accept without a defined urgent microbial threat
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
Animals30-50 people
200-400 people3000-5000 people
Goals of vaccine Trial process
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
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?”
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
Drive for Vaccine development
Benefit to mankind
Profit
The big Three vs neglected diseases
HIV
Malaria
TB
Hookworm disease
Schistosomiasis
MoneyTime
SuccessProfit
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
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”
Bioterrorism
Boom in the Vaccine development
Project Bioshield
Goals of Project Bioshield
Accelerate the R & D on vaccines Purchase Availability of priority medical countermeasures to protect the US population
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”
To improve child health in poorest countries
GAVI ALLIANCE
Innovative partnership for benefit of mankind
Bill and Melinda Gates foundation
The largest transparently operated charitable foundationin the world
Malaria Vac I
Childrens Vac I
HIV
WARREN BUFFET
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
24.3
22.6
21.3
17.8
8.15.9
•Novartis/•Chiron*
•GSK
•Wyeth
•Merck**
•Sanofi-Aventis**
•Oth
er
Growing market with a restricted number of mostly US-prone vaccine players
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)
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
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
Vaccine research shouldn’t stop there
Thank you
“ We cannot be a strong nation unless we are a healthy nation“