Lecture 4 - Vaccine Delivery & Adjuvants

Lecture 4 - Vaccine Delivery & Adjuvants - VACCINE...

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EVO VACCINE DELIVERY ADJUVANTS Edwin Oaks, Ph.D. George Mason University Fall 2008
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EVO VACCINE DELIVERY Delivery system must stimulate an effective immune response Local immunity Mucosal » Lungs, intestine, genitourinary tract, nasal tract Systemic » blood Memory Upon infection host will respond with rapid and elevated response Long - lasting Effective levels of neutralizing antibody are maintained
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EVO VACCINE DELIVERY, 2 Vaccine induced immune response is most effective if it Mimics natural immunity Antigen specificity is same Type of immune response is same T cell response Antibody response So how is the proper (effective) immune response stimulated?
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EVO
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EVO Lymphocyte Recirculation
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EVO Lymph Nodes Small bean shaped structures lying along course of lymphatics (neck, axillae, groin, para-aortic regions) Function: 1) Phagocytic cells act as filters for particulate matter and microorganisms 2) Antigen is presented to Immune system. T cells & APCs B cells
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EVO Types of Vaccines Live attenuated vaccines Inactivated vaccines Subunit vaccines Recombinant vaccines DNA vaccines Transgenic plant vaccines Each type of vaccine requires a unique delivery system
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EVO Live Attenuated Vaccines Live attenuated vaccines Pathogen is weakened or attenuated - no longer able to cause disease but maintains immunogenicity Some older live attenuated vaccines do not have carefully defined deletions Basis of attenuation is not always understood Derived by » serial passage in vitro » Random chemical mutagenesis Today, attenuation is produced by deleting gene(s) encoding one or more virulence or metabolic factors from the wild-type organism. Well-defined deletions
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EVO Live Attenuated Vaccines, cont. Live attenuated vaccines with mutation in virulence gene Delete ctx gene (encodes cholera toxin) in Vibrio cholera Mutate genes encoding critical metabolic factors Delete aro genes in Salmonella Can’t synthesize aromatic amino acids Reversion of live-attenuated vaccines back to wild -type pathogen Has happened in past (oral polio vaccine) Minimized by using large deletions Deleting two distant genes Live attenuated vaccines are usually administered by the natural route of infection
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EVO Live Attenuated Vaccines Oral route Oral polio vaccine Injection Smallpox Measles, mumps, rubella Varicella Nasal Influenza vaccine (Flumist) Problems with live attenuated vaccines Revert to virulence May not be attenuated enough May cause side effects (adverse events) Problem for people with immune deficiencies May be attenuated too much No longer able to stimulate proper immune response
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EVO Inactivated Vaccines Inactivation process Kills pathogen no longer chance of reversion No longer able to replicate » May require higher doses and repeated doses Must maintain immunogenicity and safety
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This note was uploaded on 04/29/2009 for the course BIOL 420 taught by Professor Edwardsoaks during the Fall '08 term at George Mason.

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Lecture 4 - Vaccine Delivery & Adjuvants - VACCINE...

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