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.

How does vaccination work? Expose the patient to an Antigen A live or inactivated substance (e.g., protein, polysaccharide) derived from a pathogen (e.g bacteria or virus) capable of producing an immune response

How does vaccination work? Expose the patient to an Antigen A live or inactivated substance (e.g., protein, polysaccharide) derived from a pathogen (e.g bacteria or virus)capable of producing an immune response If the patient is subsequently exposed to infectious agent carrying this Antigen they will mount a faster immune response

Carrying antigens A and B It works like this Patient exposed to pathogen Carrying antigens A and B Molecular Biology of the Cell Alberts et al

Vaccines can be divided into two types Live attenuated Inactivated

Inactivated Vaccines fall into different categories Whole viruses bacteria Individual proteins from pathogen Pathogen specific complex sugars Fractional

Live Attenuated Vaccines have 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

Live Attenuated Vaccines also 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

A number of the vaccines you received were live Attenuated Vaccines Viral measles, mumps, rubella, vaccinia, varicella/zoster, yellow fever, rotavirus, intranasal influenza, oral polio Bacterial BCG (TB), oral typhoid

Inactivated Vaccines are the other option Pluses No chance of recreating live pathogen Less interference from circulating antibody than live vaccines

Inactivated Vaccines are the other option Minuses Cannot replicate and thus generally not as effective as live vaccines Usually require 3-5 doses Immune response mostly antibody based

Inactivated Vaccines are also a common approach today Whole-cell vaccines Viral polio, hepatitis A, rabies, influenza* Bacterial pertussis*, typhoid* cholera*, plague* *not used in the United States

Other Inactivated Vaccines now contain purified proteins rather than whole bacteria/viruses Proteins hepatitis B, influenza, acellular pertussis, human papillomavirus, anthrax, Lyme Toxins diphtheria, tetanus

Modern molecular biology has offered new approaches to make vaccines Clone gene from virus or bacteria and express this protein antigen in yeast, bacteria or mammalian cells in culture

Modern molecular biology has offered new approaches to make vaccines 2. Clone gene from virus or bacteria Into genome of another virus (adenovirus, canary pox, vaccinia) And use this live virus as vaccine

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

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

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?