vaccine

Vaccines & Antibiotics

So tell me, this physician of whom you were just speaking,Is he a money maker, an earner of fees, or a healer of the sick?

Plato, The Republic

• The time: 500 B.C.

• The place: Greece

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.

Fast forward 2300 years

pathmicro.med.sc.edu/ppt-vir/vaccine.ppt

I had a brilliant idea


He always takes all the credit!

Vaccination

• Charles Jenner 1796 : Cowpox/Swinepox

• 1800’s Compulsory childhood vaccination

What is variolation?

• Patients were exposed to ground smallpox pustules--- generally inhaled the pustules. The patients suffered from very mild cases of smallpox were protected against later cases. Occasionally variolated patients developed severe cases.

• Variolated people could transfer severe cases of smallpox to unvariolated people

•

Smallpox

•1% v. 25% mortality

•Life-long immunity


Variolation was a huge advance

Smallpox

•


Smallpox presented many advantages that made this possible

Smallpox• No animal reservoir

• Lifelong immunity

• Subclinical cases rare

• One Variola serotype

•


Smallpox presented many advantages that made this possible

SmallpoxAs a result, after a world-wide effort

Smallpox was eliminated as a human disease in 1978


Edward Jenner British physician who was

variolated as boy

Performed controlled experiments on cowpox inoculation offered protection against smallpox

King Carlos IV commanded Francisco

Xavier Balmis to take smallpox vaccine to Spain colonies in the New World

Louis Pasteur Developed vaccines for

cholera, anthrax, and rabies using weakened pathogens

Rep

ort

ed c

ases

per

100

000

po

pu

lati

on

100

10

1

0.1

0.001

0.01

1950 1960 1970 1980 1990

Inactivated (Salk) vaccine

Oral vaccine

Cases per 100,000 population United States

Other vaccines have followed,making once feared diseases a thing of the past

Why vaccinate?Individual protection

Herd immunity

Herd Immunity

• Resistance of a group to infection due to immunity of a high proportion of the members of the group.

• Immunity in some individuals protects non-immune individual from infection

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

What is antigen?

•A substance that is recognized as foreign and that stimulates the production of antibodies.

Expose the patient to an Antigen

If the patient is subsequently exposed to virus carrying this Antigen they willmount a faster immune response

How does vaccination work?

Not immunized but healthy

Not immunized, sick, and contagious

Immunized

Which do we belong?

Or in more detail….

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 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

• 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

Polio Vaccine illustrates the pluses and minuses of

live vaccines


Sabin Polio VaccineAttenuated by passage in foreign host (monkey kidney cells)

Selection to grow in new host makes virus

less suited to original host

Modern molecular biology

has offered new approaches to make

vaccines

Modern molecular biologyhas offered new approaches to make vaccines

1. Clone gene from virus or bacteria and express this protein antigen in yeast, bacteria or mammalian cells in culture

Modern molecular biologyhas 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

To begin we need to ask some key questions

What should vaccine elicit?

Neutralizing antibodies

to kill free virus




to kill free virus

T cell response to

kill infected cells

OR




to kill free virus

T cell response to

kill infected cells

OR

OR BOTH?

This prompted an experimentthat demonstrated

the feasibility of a vaccine

This prompted an experimentthat demonstrated

the feasibility of a vaccine

December 1992: Live attenuated SIV vaccine

Lacking the gene Nef

protected all monkeys for 2 years against massive dose of virus

• All controls died

• cell mediated immunity was key

I don’t know about youbut I was pretty happy about that!

However, this approach is still viewed as too risky to

try on human subjects

December 1992: Live attenuated SIV vaccine

Lacking the gene Nef

protected all monkeys for 2 years against massive dose of virus

• All controls died

• cell mediated immunity was key

The next efforts attempted touse recombinant viral proteins as antigens

in an effort to generate neutralizing antibodies

The next approach involved usingviral vectors to try to

also boost the T cell response

Many different viral vectors are being investigated but this trial used the human cold virus called

adenovirus

vaccine

Documents

severe cases of smallpox

mild cases of smallpox

variolated people

smallpox vaccine

later cases

variolated patients

vaccines antibioticsso

ground smallpox pustules