Transcript Viral Vaccines - Molecular Immunology

Vaccines
Immunity
Specific defenses
Immunity
Active immunity
Following clinical infection
Passive immunity
natural
Following subclinical infection
Transfer of maternal
Antibodies Through placenta
Transfer of maternal
Antibodies Through milk
acquired
Following vaccination
Following administration of
Immunoglobulin or antiserum
Active immunity
• Resistance developed in response to stimulus
by an antigen (infecting agent or vaccine) and
is characterized by the production of
antibodies by the host.
Passive immunity
• Immunity conferred by an antibody produced
in another host. It may be acquired naturally
or artificially (through an antibody-containing
preparation).
Immunizing agents
Immunizing agents
vaccines
immunuglobulins
antisera
Vaccination
• Vaccination is a method of giving antigen to
stimulate the immune response through active
immunization.
• A vaccine is an immuno-biological substance
designed to produce specific protection against a
given disease.
• A vaccine is “antigenic” but not “pathogenic”.
Let’s go back in time to see
how this strategy works
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
Vaccination
• Charles
Jenner 1796 :
Cowpox/Swinepox
• 1800’s Compulsory childhood
vaccination
Smallpox
•1% v. 25% mortality
•Life-long immunity
• UK: 1700’s
• China 1950
• Pakistan/Afghanistan/
Ethiopia 1970
pathmicro.med.sc.edu/ppt-vir/vaccine.ppt
Smallpox presented many advantages that made this possible
• No
animal reservoir
• Lifelong immunity
• Subclinical cases rare
• Infectivity does
not precede overt symptoms
• One 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
pathmicro.med.sc.edu/ppt-vir/vaccine.ppt
Types of vaccines
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Live vaccines
Attenuated live vaccines
Inactivated (killed vaccines)
Toxoids
Polysaccharide and polypeptide (cellular
fraction) vaccines
• Surface antigen (recombinant) vaccines.
Live vaccines
• Live vaccines are made from live infectious
agents without any amendment.
• The only live vaccine is “Variola” small pox
vaccine, made of live vaccinia cow-pox virus
(not variola virus) which is not pathogenic but
antigenic, giving cross immunity for variola.
Live attenuated (avirulent) vaccines
• Virulent pathogenic organisms are treated to become
attenuated and avirulent but antigenic. They have
lost their capacity to induce full-blown disease but
retain their immunogenicity.
• Live attenuated vaccines should not be administered
to persons with suppressed immune response due
to:
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Leukemia and lymphoma
Other malignancies
Receiving corticosteroids and anti-metabolic agents
Radiation
pregnancy
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 (killed) vaccines
• Organisms are killed or inactivated by heat or
chemicals but remain antigenic.
• They are usually safe but less effective than
live attenuated vaccines.
• The only absolute contraindication to their
administration is a severe local or general
reaction to a previous dose.
Inactivated Vaccines
Minuses
• Cannot replicate and thus generally not as
effective as live vaccines
• Usually require 3-5 doses
• Immune response mostly antibody based
Inactivated Vaccines
Pluses
• No chance of recreating live pathogen
• Less interference from circulating antibody than
live vaccines
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
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
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
• Grows in epithelial cells
• Does not grow in nerves
• No paralysis
•Local gut immunity (IgA)
Salk Polio Vaccine
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Formaldehyde-fixed
• No reversion
Polio Vaccine illustrates the pluses and minuses of
live vaccines
US: Sabin attenuated vaccine
~ 10 cases vaccine-associated polio per year =
1 in 4,000,000 vaccine infections
Scandinavia: Salk dead vaccine
• No gut immunity
• Cannot wipe out wt virus
pathmicro.med.sc.edu/ppt-vir/vaccine.ppt
Live virus generates a more complete immune response
512
Killed (Salk)
Vaccine
Live (Sabin)
Vaccine
Serum IgG
Serum IgG
Reciprocal virus antibody titer
128
32
Serum IgM
Serum IgM
Nasal
IgA
Serum IgA
8
Serum IgA
2
Duodenal
IgA
Nasal and
duodenal IgA
1
Vaccination
4
8
96
Days Vaccination
48
9
6
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
Cloned protein antigens
have pluses and minuses
Pluses
•Easily manufactured and often relatively stable
•Cannot “revert” to recreate pathogen
Minuses
• Poorly immunogenic
• Post-translational modifications
• Poor CTL response
Viral vectors
have pluses and minuses
Pluses
• Infects human cells but some do not replicate
• Better presentation of antigen
• Generate T cell response
Minuses
•Can cause bad reactions
•Can be problems with pre-exisiting immunity to virus
•Often can only accommodate one or two antigens
Toxoids
• They are prepared by detoxifying the exotoxins of
some bacteria rendering them antigenic but not
pathogenic. Adjuvant (e.g. alum precipitation) is used
to increase the potency of vaccine.
• The antibodies produces in the body as a
consequence of toxoid administration neutralize the
toxic moiety produced during infection rather than
act upon the organism itself. In general toxoids are
highly efficacious and safe immunizing agents.
Polysaccharide and polypeptide (cellular
fraction) vaccines
• They are prepared from extracted cellular fractions
e.g. meningococcal vaccine from the polysaccharide
antigen of the cell wall, the pneumococcal vaccine
from the polysaccharide contained in the capsule of
the organism, and hepatitis B polypeptide vaccine.
• Their efficacy and safety appear to be high.
Surface antigen (recombinant) vaccines.
• It is prepared by cloning HBsAg gene in yeast
cells where it is expressed. HBsAg produced is
then used for vaccine preparations.
• Their efficacy and safety also appear to be
high.
Types of vaccines
Live
vaccines
Live
Killed
Attenuate Inactivated
d vaccines vaccines
•Small pox
variola
vaccine
•BCG
•Typhoid
oral
•Plague
•Oral polio
•Yellow
fever
•Measles
•Mumps
•Rubella
•Intranasal
Influenza
•Typhus
Toxoids
Cellular fraction Recombinant
vaccines
vaccines
•Typhoid
•Diphtheria •Meningococcal •Hepatitis B
polysaccharide vaccine
•Cholera
•Tetanus
vaccine
•Pertussis
•Pneumococcal
•Plague
polysaccharide
•Rabies
vaccine
•Salk polio
•Hepatitis B
•Intrapolypeptide
muscular
vaccine
influenza
•Japanise
encephalitis
Routes of administration
• Deep subcutaneous or intramuscular route
(most vaccines)
• Oral route (sabine vaccine, oral BCG vaccine)
• Intradermal route (BCG vaccine)
• Scarification (small pox vaccine)
• Intranasal route (live attenuated influenza
vaccine)
Scheme of immunization
• Primary vaccination
– One dose vaccines (BCG, variola, measles, mumps,
rubella, yellow fever)
– Multiple dose vaccines (polio, DPT, hepatitis B)
• Booster vaccination
To maintain immunity level after it declines after
some time has elapsed (DT, MMR).
Periods of maintained immunity due to
vaccines
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Short period (months): cholera vaccine
Two years: TAB vaccine
Three to five years: DPT vaccine
Five or more years: BCG vaccine
Ten years: yellow fever vaccine
Solid immunity: measles, mumps, and rubella
vaccines.
Levels of effectiveness
• Absolutely protective(100%): yellow fever vaccine
• Almost absolutely protective (99%): Variola, measles,
mumps, rubella vaccines, and diphtheria and tetanus
toxoids.
• Highly protective (80-95%): polio, BCG, Hepatitis B,
and pertussis vaccines.
• Moderately protective (40-60%) TAB, cholera
vaccine, and influenza killed vaccine.