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

I had a brilliant idea

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

He always takes all the credit!

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

Vaccination
Charles Jenner 1796 :

Cowpox/Swinepox
1800s 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

Variolation was a huge advance

Smallpox

1% v. 25% mortality
Life-long immunity

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

Smallpox presented many advantages that made this possible

Smallpox

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

Smallpox presented many advantages that made this possible

Smallpox
No animal reservoir
Lifelong immunity
Subclinical cases rare
One Variola serotype

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

As a result, after a world-wide effort

Smallpox was eliminated
as a human disease in 1978
Smallpox

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

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

Other vaccines have followed,

making once feared diseases a thing of the past

Reported cases per 100000 population

100

Inactivated
(Salk) vaccine

Cases per 100,000

population United
States

10

Oral
vaccine
1

0.1

0.01
0.00
1

1950

1960

1970

1980

1990

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?
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

What is antigen?

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

How does vaccination

work?
Expose the patient to an Antigen

If the patient is subsequently

exposed to virus carrying
this Antigen they will
mount a faster immune
response

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
Whole
viruses
bacteria
Fractional

Individual proteins from pathogen

Pathogen specific complex sugars

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

Polio Vaccine illustrates the

pluses and minuses of live
vaccines

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

Sabin Polio Vaccine

Attenuated 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 biology

has 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 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

To begin we need to
ask some key questions
What should vaccine elicit?

Neutralizing antibodies
to kill free virus

To begin we need to
ask some key questions
What should vaccine elicit?

Neutralizing antibodies
to kill free virus

OR

T cell response to
kill infected cells

To begin we need to
ask some key questions
What should vaccine elicit?

Neutralizing antibodies

OR

to kill free virus

T cell response to
kill infected cells

OR BOTH?

This prompted an experiment

that demonstrated
the feasibility of a vaccine

This prompted an experiment

that demonstrated
the feasibility of a vaccine
I dont know about you
but I was pretty happy about that!

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

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 to

use recombinant viral proteins as antigens
in an effort to generate neutralizing antibodies

The next approach involved using

viral 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