April 3.docx

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Cell and Systems Biology
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Gray- Owen

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Vaccines and Vaccine Development – April 3, 2013 How does a vaccine then go from lab to people? Cannot produce enough for every single person on the planet – how do determine criteria that determines who gets vaccine so maximize protection? Causes of death in children under 5 years of age Ex. Measles – there are safe, effective vaccines available but not reaching the children that need them The problem with controlling infectious disease in some case is the ability to provide the product in enough quantity to give to people that need it Human vaccines – viral and bacterial infections Prostate cancer – vaccine candidates are being developed for chornic, non-infecitous disease Increasingly difficult Easy targets – amenable to technological approaches developed 30-40 years ago – sufficiently large market Still large list of pathogens that represent reasonable targets for vaccine development HIV, HCV – antigenic diversity – diversity of strains – rhinoviruses (like poliovirus, both picornaviruses but there are 3 strains of poliovirus) has 120 strains or so – rhinovirus is not life-threatening – little incentive, but technology to do so is available Pathogen has complex life cycle that allows them to elaborate sophisticated immune strategies – chlamydia, gonorrhea, herpes – all adept at establishing infections and evading protective host immune responses – run into problem of wondering what immune response wanted to elicit Pathogens can evoke immune response that is pathologic, not protective – ex. SARS – normal infections with coronaviruses are beign, but SARS caused runaway cytokine storm that caused profound inflammation in infected people’s lungs – RSV is common pathogen of children – potential for vaccine elicted immunopathology (children immunized with killd RSV are at risk of severe, potentially fatal infection, following exposure to live virus); dengue Four simple quadrants – Meningococcal, streptococcal vaccines – technically easy, high need/value?????? Tropical parasites of low value; leishmaniasis DESIGNING NEW VACCINES Product developed if investment seems likely to be paid back or if charity is willing to subsidize Social environment and benefit of using vaccine should be commensurate with cost of developing and providing vaccine to people in need of product Always the risk of new strains of flu appearing and spreading globally – causing pandemic – where and where these strains will arise not predictable Second drive is necessity to improve old vaccines – improve safety and tolerability of vaccines – ex. Pertussis vaccine were effective but children developed large areas of inflammation at site of injection Purified proteins of pertussis less reactogenic – but less protective – resurgence of pertussis Administered to children as four or five vaccines given in single immunization – triple MMR, pentameric – developing these combination products is – Stability of vaccine – particularly a problem with providing product to developing world – many vaccine antigens are not intrinsically stable to heat/storage over prolonged period of time – vaccine formulation needs to include an agent stabilizing the product, maintain integrity and efficacy of vaccine Some of the products – many rely on cold storage in refrigerator providing an uninterrupted chain of refrigeration Non-governmental organizations, WHO, UNICEF, Gates Foundation – spend lots of money to ensure that vaccines are provided to children in developing countries since the native governments unable to pay for vaccine – Vaccines are developed by commercial companie
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