Future Challenges for Vaccines

1. Future Challenges for Vaccines Many challenges still to be solved Emerging & re-emerging infections Antigenic variation Societal impact of vaccines Opposition to vaccines Safety & risk Poverty related disease In the short time in human history since vaccines have been introduced on a global scale they have changed the world Rembrandt van Rijn. The Rat Catcher (1632)

2. 1. Emerging & re-appearing infectious disease • During the 20th century, infectious diseases remain among the leading causes of death worldwide for three reasons: • emergence of new infectious diseases • re-emergence of old infectious diseases • persistence of intractable infectious diseases

3. Emerging/Re-emerging Infectious Disease

4. New infectious diseases continue to evolve & "emerge.” • Changes in human demographics, behavior, land use, etc. are contributing to new disease emergence by changing transmission dynamics to bring people into closer and more frequent contact with pathogens. • Vaccines for these disease will take time to develop & license

5. 2. Antigenic diversity & variation • Antigenic diversity is an escape strategy for pathogens to avoid immune responses • Vaccines must include the diverse antigens to be successfully protective • Antigenic variation in pathogens can occur over time. It can be fast or slow and reflect the rate of mutation but is a means for avoiding specific immunity • E.g. HIV, Hepatitis C, malaria • Success of vaccination varies if the pathogen’s antigens change

6. Antigenic variation is widespread • True natural antigenic variation has been demonstrated in many pathogens, including Neisseria gonorrhoeae, Mycoplasma spp, Pneumocystis carinii, and Giardia lamblia. • The complete genomic sequences of other pathogenic bacteria, such as Helicobacter pylori, Treponema pallidum, and Mycobacterium tuberculosis, includes families of repeated genes that are polymorphic in sequence and may be involved in antigenic variation.

7. Antigenic variation- tricks the host (& vaccine designer) • Antigenic variation has important implications for the development of vaccine. • The vaccine needs to be multivalent (directed against multiple antigens), perhaps to the point of impracticality. • If the infected host animal has not solved the problem of identifying an antigen that is conserved among the variants, how can vaccine developers hope to do this? • If variant strains replace the one targeted by vaccines then the disease is no longer controlled

8. Antigenic variation in influenza A • Influenza A virus is able to persistently re-infect human populations by continually evading host immunity through the continuous and rapid evolution of surface antigens haemagglutinin (H) and neuraminidase(N). This process is known as antigenic drift. • A vaccine directed against one type of influenza virus (e.g. H3N2) does not protect against infection with a different antigenic type (e.g. H5N1).

9. 3. Societal impact of of vaccines • Vaccination of a large population can lead to protection of the entire population due to the “herd effect” • Fewer infected people means reduced transmission of infection • Thus wide vaccination cover can protect those who are not vaccinated such as very small babies because the level of vaccination reduces the risk of transmission of the disease.

10. 4. Opposition to vaccines • The success of vaccines in controlling & eliminating childhood infections had led to the revival of the anti-vaccination movement. • Many people have no knowledge or memory of the real impact of the full-blown disease • They do not perceive any risk to them or their child for these infections nor value the protection of a vaccine • Their suspicion or belief that the risk of adverse events is greater than the risk of full-blown disease has led to breakdown of confidence

11. 5. Safety & risk • Immunisation are among the safest & most cost effective public health interventions • No vaccine however is completely safe or effective • Close monitoring of adverse events is very important to the maintenance of confidence and sufficient vaccination coverage to provide herd immunity • The development of vaccines has reached a high level of complexity where safety concerns need to be addressed correctly

12. 5. Safety & risk • A great challenge is the need to rapidly and cost-effectively determine the safety and efficacy of new vaccines • Vaccine trials are long, complex and expensive. • Due to these costs some new vaccines appear as low-profit products that although useful may never be licensed • The risk of litigation outweighs the cost of development • The public in the developed world requires an almost zero-risk product • For these reason the level of safety requirement has increased enormously for new vaccines when compared with traditional vaccines • The time to market and cost of development have increased in parallel

13. Life Cycle of an immunisation program 5. At this point, most people have not experienced the disease, and they worry about about possible side-effects of the vaccine. People may start to question whether the vaccine is necessary or safe, and some people will stop getting immunized. 6. If enough people stop getting immunized, disease numbers will start to rise again, and there will be outbreaks. 7. People are reminded of how bad the disease can be, and turn back to immunization to avoid it.

14. Adverse event reporting in USA • The Vaccine Adverse Event Reporting System is a cooperative program for vaccine safety of the Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA). VAERS is a post-marketing safety surveillance program, collecting information about adverse events (possible side effects) that occur after the administration of US licensed vaccines. • This Web site provides a nationwide mechanism by which adverse events following immunization (AEFI) may be reported, analyzed and made available to the public. • The VAERS Web site also provides a vehicle for disseminating vaccine safety-related information to parents/guardians, healthcare providers, vaccine manufacturers, state vaccine programs, and other constituencies.

15. Adverse eventsFrequency of some scientifically proven serious reactions to vaccines

16. Real adverse events - errors in manufacture • Besides the potentially serious reactions caused by the vaccines themselves, adverse events due to “programmatic errors” occur. E.g. • Use of wrong diluent • Transmission of pathogens due to poor aseptic technique • Incomplete inactivation of virus or bacterium (vaccine is virulent) • Modern methods of manufacture & quality control (Good Manufacturing Practice/GMP) aim to catch these errors before they cause harm

17. Unproven adverse events - associations between vaccine & health conditionsall unproven - some examples of myths believed to be true by public

18. Epidemiological studies to investigate suggested associations

19. Epidemiological studies to investigate suggested associations

20. 6. Poverty related disease • Inequity in disease burden is related to poverty • The healthier a population the more the adults can contribute to productive activity and children are brought up in a stable environment • Income is directly related to health; • Fertility • Education • Productivity • Strategies such as vaccination that sustain good health promote non-medical benefits to the population; • Smaller, more affordable families • High priority for education • Savings & investment for the future • Longer, productive working lives • Lower health costs

21. 6. Poverty related diseases • implementation of sustainable vaccination programs in poor countries remains a problem • Cost • Social disruption (eg AIDS affected adults) • Logistical difficulty (infrastructure, cold-chain, trained staff) • Poor governance (lack of management, record-keeping) • Instability (war and disaster) • Global Alliance for Vaccination & Immunization (GAVI) is an alliance of financiers, vaccine developers & manufacturers, governments, agencies (UNICEF, WHO) and donors (Bill & Melinda Gates Foundation) to collectively fund & solve some of these problems

24. Challenge for relevant use of vaccines in the future • Better information and communication are the keys to relevant use of vaccines • For individuals • For parents • For health professionals • For bureaucrats • For governments • For transnational health agencies • For major donors • Science informs and innovates but people decide