Post on 25-Dec-2015
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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
pathmicro.med.sc.edu/ppt-vir/vaccine.ppt
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
pathmicro.med.sc.edu/ppt-vir/vaccine.ppt
Variolation was a huge advance
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
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
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
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
pathmicro.med.sc.edu/ppt-vir/vaccine.ppt
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 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?
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