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?

• 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

• 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?

Molecular Biology of the Cell Alberts et al

Patient exposed to pathogenCarrying antigens A and B

It works like this

Vaccines can be divided into two types

• Live attenuated

• Inactivated

Inactivated Vaccines fall into different categories

• viruses• bacteria

• Individual proteins from pathogen• Pathogen specific complex sugars

Whole

Fractional

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

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

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

Inactivated Vaccines are the other option

• No chance of recreating live pathogen

• Less interference from circulating antibody than live vaccines

Pluses

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

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

Other Inactivated Vaccinesnow contain purified proteins

rather than whole bacteria/viruses

• Proteins hepatitis B, influenza,acellular pertussis,

human papillomavirus, anthrax, Lyme

• Toxins diphtheria, tetanus

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

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

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?