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Even 2,500 Years Ago, People Knew Immunity Worked.
• Greek physicians noticed that people who survived smallpox never got it again.
• The insight: Becoming infected by certain diseases gives immunity.
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How does vaccination work?
• A live or inactivated substance (e.g., protein, polysaccharide) derived from a pathogen (e.g bacteria or virus) capable of producing an immune response
Expose the patient to an Antigen
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• A live or inactivated substance (e.g., protein, polysaccharide) derived from a pathogen (e.g bacteria or virus)capable of producing an immune response
Expose the patient to an Antigen
If the patient is subsequently exposed to infectious agent carrying this Antigen they will mount a faster immune response
How does vaccination work?
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Molecular Biology of the Cell Alberts et al
Patient exposed to pathogenCarrying antigens A and B
It works like this
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Vaccines can be divided into two types
• Live attenuated
• Inactivated
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Inactivated Vaccines fall into different categories
• viruses• bacteria
• Individual proteins from pathogen• Pathogen specific complex sugars
Whole
Fractional
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Live Attenuated Vaccineshave several advantages
• Attenuated (weakened) form of the "wild" virus or bacterium
• Can replicate themselves so the immune response is more similar to natural infection
• Usually effective with one dose
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Live Attenuated Vaccinesalso have several
disadvantages• Severe reactions possible
especially in
immune compromised
patients
• Worry about recreating
a wild-type pathogen
that can cause disease
• Fragile – must be
stored carefully
MMWR, CDC
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A number of the vaccines you receivedwere live Attenuated Vaccines
• Viral measles, mumps,rubella, vaccinia,
varicella/zoster, yellow fever,
rotavirus, intranasal influenza, oral polio
• Bacterial BCG (TB), oral typhoid
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Inactivated Vaccines are the other option
• No chance of recreating live pathogen
• Less interference from circulating antibody than live vaccines
Pluses
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Inactivated Vaccines are the other option
• Cannot replicate and thus generally not as effective as live vaccines
• Usually require 3-5 doses
• Immune response mostly antibody based
Minuses
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Inactivated Vaccines are alsoa common approach today
• Viral polio, hepatitis A, rabies, influenza*
• Bacterial pertussis*, typhoid*cholera*, plague*
Whole-cell vaccines
*not used in the United States
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Other Inactivated Vaccinesnow contain purified proteins
rather than whole bacteria/viruses
• Proteins hepatitis B, influenza,acellular pertussis,
human papillomavirus, anthrax, Lyme
• Toxins diphtheria, tetanus
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Modern molecular biologyhas offered new approaches
to make vaccines
1. Clone gene from virus or bacteriaand express this protein antigenin yeast, bacteria or mammalian cells in culture
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Modern molecular biologyhas offered new approaches
to make vaccines
2. Clone gene from virus or bacteriaInto genome of another virus (adenovirus, canary pox, vaccinia)And use this live virus as vaccine
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This allows T cells to recognize HIV infected cells,for example, and even internal proteins
like reverse transcriptase can serve as antigens
An effective vaccine must get around the strategies HIV uses to evade the immune system
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To begin we need to ask some key questions
What should vaccine elicit?
Neutralizing antibodies
to kill free virus
T cell response to
kill infected cells
OR
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To begin we need to ask some key questions
What should vaccine elicit?
Neutralizing antibodies
to kill free virus
T cell response to
kill infected cells
OR
OR BOTH?