Vaccines “Material producing an immune reaction and an acquired immunity to a natural microorganism” Dictionary of Biology, 1995
“Immunisation is the most generally applicable way of preventing infectious disease. The control of so many important ... diseases by immunisation is arguably the most outstanding medical achievement of the twentieth century, recognised by the award of several Nobel prizes” White & Fenner, Medical Virology, 1994
VACCINES • One of the most important inventions ever • Some of the most deadly diseases of recent times have been controlled by vaccination
What is a Vaccine? • Classical Vaccines can be • crippled or weakened organisms • dead organisms (inactivated vaccines) • individual proteins or other subunits • A vaccine is introduced into people to give a protective immune response that mimics natural infection without causing disease = SAFE.
Why Have Vaccines? “Every year, up to three million children's lives are saved by immunization“ http://www.vaccinealliance.org/
Vaccine Preventable Diseases http://www.who.int/home/map_ht.html#Vaccine Preventable Diseases
ERADICATION OF SMALLPOX - THE MOST SUCCESSFUL VACCINE CAMPAIGN EVER • Most people with smallpox would die or be severely disfigured or blinded • In 1967 there were 10 million cases of small pox in 44 countries - 250 million vaccine doses were needed each year • WHO decided to get rid of smallpox by embarking on a vaccine campaign to cover the whole planet • The last cases of smallpox were in Somalia in 1977 and in UK in 1978 (lab escape).
Somalia, 1977 - Ali Maalim, last recorded case of naturally-caused smallpox http://www.cdc.gov/od/ogh/smallmaa.htm
WHY DID THE SMALLPOX ERADICATION CAMPAIGN WORK? • Effective vaccine which protected for many years • Smallpoxvirus did not have a host besides man • Symptoms of disease easy to identify - few subclinical cases and no reinfections • It was such a dreaded disease that most people wanted to be vaccinated • GOVERNMENTS GOT INVOLVED • VACCINATION WAS FREE
Poliomyelitis - Eradication in the New Millenium? • Dreadful disease causing paralysis - in the 1950s many people were put in iron lungs in developed countries (and died elsewhere) • In the late 1950s a vaccine became available • Poliomyelitis is almost eradicated!!
Press Release WHO/21 9 April 1999 POLIO OUTBREAK IN CENTRAL AFRICA WHO mounts outbreak control campaign to vaccinate 700,000 children The World Health Organization today confirmed that the cause of an outbreak of paralysis among children living in Angola, Central Africa, was polio. A WHO mission team has been despatched to work with the Ministry of Health to control the outbreak.
Things your children won’t have to worry about...
A cartoon history of the polio vaccine story from the US PBS Network: the story starts in a newspaper office, in 1954…. http://www.pbs.org/wgbh/aso/ontheedge/polio/index.html
In 1988, the 41st World Health Assembly - 166 Member States - launched a global initiative to eradicate polio by the end of the year 2000. • In 11 years the number of cases has fallen by more than 90 percent from an estimated 350 000 cases (and even further since). • Widely endemic on five continents in 1988, polio is now concentrated only in parts of the Indian sub-continent - and now Africa, again!
Polio eradication is based on four strategies: • Routine immunization of infants starting with four doses of oral live polio vaccine in the first year of life; • National Immunization Days (NIDs), which vaccinate all children FREE under five years of age (2 rounds per year for at least three consecutive years) • Effective disease surveillance • House-to-house 'mopping-up' to ensure that every child is vaccinated. • The target date for certification of the world as polio-free WAS 2005….
Hepatitis More than 2 billion people alive today have at some time been infected with the hepatitis B virus (HBV). Of these, about 350 million remain chronically infected carriers. Every year there are over 4 million acute clinical cases of hepatitis B and about a million deaths. Get vaccinated! Hepatitis B is preventable. Recombinant / killed vaccine
Hepatitis A KILLED WHOLE- VIRUS VACCINE • The virus is spread through the faecal-oral route, most often through person-to-person transmission. It may also be spread through contaminated food or water. • An estimated 1.4 million cases of HAV infection occur worldwide each year. The overall case fatality rate is estimated to be 0.3%. http://www.cdc.gov/ncidod/diseases/hepatitis/slideset/httoc.htm
Influenza KILLED WHOLE-VIRUS VACCINE
The eggshell is cracked, and the influenza virus is injected into the fluid surrounding the embryo. The egg is resealed, the embryo becomes infected, and the resulting virus is then harvested, purified and used to produce the vaccine.
For the Northern Hemisphere, the flu season typically runs from November through March. Based on collected virus samples and infection activity, the World Health Organization decides which influenza strains to include in a vaccine in mid-February. By mid-March, high-growth strains of vaccine virus are provided to manufacturers, and the materials needed to test the identity and potency of the resulting vaccine are supplied in mid-May. Vaccines become available in clinics in October. Number of U.S. flu cases per season: 29 million to 58 million Number of Americans hospitalized per season: 114,000 Number of deaths: 36,000 Number of vaccine doses produced this season: 87.1 million
Nature (26 May 2005) [Erica] Check explains that pharmaceutical companies have little incentive to invest large sums of money making a vaccine for a pandemic that might never happen. … Developing countries in Asia, which are most likely to be the source of pandemic, have little capacity to make vaccines or buy stocks from other countries.
Nature435, 390-391 (26 May 2005) Bird flu spreads among Java's pigs David Cyranoski, Tokyo Abstract Indonesian government scrambles to track disease. Concerns over the presence of a dangerous strain of avian flu virus in Indonesia's pigs are growing, as government tests confirm the existence of infection. In some areas, the H5N1 virus could be infecting up to half of the pig population, without causing any signs of disease. Nature (26 May 2005) Editorial: To stimulate an increase in capacity, we need health policies that boost demand for existing flu vaccines in ordinary years. The same goes for antiviral drugs. But the worst-case scenario is that a pandemic starts within two years. We would have no vaccine and few drugs, and we would be dependent on governments and the WHO to try to extinguish the first outbreaks at source. That's why the first priority must be to prevent a pandemic emerging in the first place, by extinguishing the disease in animals.
So Things are Fine…? • “...almost three million ... lives worldwide are lost from diseases that are preventable with existing vaccines.” http://www.vaccinealliance.org/
Of children who die before their fifth birthday, 98% are in the developing world. • Of people who are HIV positive, some 95% are in poor countries. • Of the millions who die prematurely of tuberculosis, malaria, measles, tetanus and whooping cough, nearly all live in the poor world. • Tuberculosis alone kills more people each year than lung cancer, the terror of the West. TheEconomist, 14th August 1999
“At present, vaccine development is based on current market demand rather than epidemiological realities.” - WHO Vaccines Report, 1996 Effective Vaccines Not Commonly Used in Developing Countries • Japanese encephalitis virus • Hib • Typhoid • Rubella* • (Cholera) • HBV • HAV
How Vaccines are Developed Preclinical development Manufacture (GMP) Clinical trials Basic research Phase I/II Phase III Laboratory Human research in vitro & animal studies Safety, Immunogenicity Exploration Discovery Efficacy Vaccine concept Experiments in rodents and primates Human trials Safety, immunogenicity Likelihood of protection in humans
Challenges for Public Health Sector to Global Vaccine Use • Safe Vaccines • Cost Effective Vaccines • Vaccine administration must be easily implemented • infants (eg routine childhood vaccines) • targeted populations (eg rubella vaccine • Vaccine Supply should be assured • Procurement and financial sustainability
36 million children not immunized (DTP3), 2001 3 million children die of EPI vaccine preventable diseases every year Source: WHO/UNICEF estimates, 2002
Global Immunisation 1980-2001, DTP3 coverage global coverage at 73% in 2001 Source: WHO/UNICEF estimates, 2002
Vaccine Safety • Vaccine production • Production quality control & safety • Batch lot consistency • Delivery systems • Needle free delivery • Multi-dose vials • Stability of vaccine (eg. cold chain) • Vaccine-related adverse events • Public perception, as much as reality
Vaccine Safety & Public Perception • Vaccine-associated perception • Autism and measles vaccine • Hepatitis B vaccine and multiple sclerosis • OPV in Nigeria today • RotaShield® and intussusception • Reported association forced withdrawal of vaccine • Resulted in new dimensions of vaccine trials for second generation candidates
Vaccine Cost-effectiveness • Global & regional burden of disease • Vaccine production costs • Purification of vaccine antigens • Quality control and regulatory costs • Filling and formulation • Clinical trials • Production plants for GMP vaccine • Competition with pharmaceutical industry • Financial sustainability - elusive $1 per dose
Vaccine Administration • Currently we have cost effective vaccines against a range of childhood illnesses • Challenge is getting the vaccine to the children who need it most • Vaccines such as measles, hepB and Hib are not yet administered routinely