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VACCINOLOGY
VACCINOLOGY
• History
• Concept of Vaccination
and Types of Vaccines
• General Principles
• Principles according to
type
• Practices
• Present status of Vaccines
[update]
HISTORY
• Lady Mary Montagu
was first to introduced
variolation in Great
Britain- 1718
Edward Jenner
First to publish and
test immunity by
challenge with
smallpox.
1796, inoculated a
person, 5 years later
vaccination became
popular.
Invented smallpox
vaccine
Dawn of Immunological
Science
1875-1910Louis Pasteur
• 1881 anthrax vaccine
was run and in 1882
85000 sheep was
immunized.
• Introduced use of
vaccinia virus
• Invented rabies
vaccine
Robert Koch
• His discovery of
Vibrio cholerae, killed
whole-cell bacterial
vaccines were
introduced in 1896
Early Bacterial Vaccines,
toxins, and toxoids [1910-1930]
• Koch’s isolation of
tubercle bacillus,
ushered the search for
a vaccine for
tuberculosis.
• 13 years after bacille
Calmette-Guerin
(BCG) was invented
• Calmette [left] Guerin
[right]
• World War I gave increased opportunity for the
killed whole-cell bacterial vaccines to make,
especially in the case of typhoid.
• 1920s a killed bacterial vaccine was used fairly
widely against Bordetella pertussis.
• 1923 Glenny and Hopkins discovered that
formalin treatment of diphtheria toxin could
render it harmless while preserving its
immunogenic potential
Early Viral Vaccines: Yellow
Fever and Influenza
[1930-1950]
• Max Theiler’s safe and effective live
attenuated yellow fever vaccine 17D, hails
from this period.
• First-generation killed whole-virus
influenza vaccines and vaccines against
typhus and Japanese B encephalitis vaccines
also hails from this period.
The tissue Culture Revolution:
Poliomyelitis, Measles, Mumps and
Rubella [1950-1970]
• On April 12 1955, the 10th anniversary of the
death of Franklin Roosevelt, the famous polio
victim, a press conference in the University of
Michigan revealed to the world that Jonas Salk’s
formalin-treated whole virus vaccine provided
protection
• between 1955 and 1961, 300 million does were
administered and incidence of polio declined
dramatically
11
• In 1965 Salk’s vaccine was replaced by Albert
Sabin’s vaccine because 149 cases of polio
occurred due to faulty production technique
• Edmondston strain of measles vaccines Enders’
original was first introduced in 1963 but was still
risky
• 1964 more attenuated Moraten an Schwartz
derivatives of the original Enders strain was
introduced.
• 1967 mumps vaccine was invented
• 1968 a live attenuated rubella vaccine was
invented
• 1969 a combined measles-mumps-rubella vaccine
was introduced and licensed in 1971
Dawn of the Molecular Era: Hepatitis
B., Pneumococcus, and Haemophilus
influenzae B. [1970-1990]
• Hepatitis B vaccine, use of the surface antigen of
the hepatitis B virus represented a new degree of
purity of a single protein as a vaccine.
• First vaccine manufactured through recombinant
DNA technology.
• First time vaccine was introduced as a expensive
vaccine for special risk groups like doctors, nurses
etc.
• Ushered in the new era where genetic engineering
approaches have become the norm in vaccine
research and development.
• Molecular vaccines of a different character
were the subunit capsular polysaccharide
vaccines against Streptococcus pneumoniae,
Neisseria meningitidis and Haemophilus
influenzae B were licensed in 1970s and
early 1980s.
• Various Hib conjugates were licensed in the
late 1980s effectively bringing us to the
modern era
Small pox eradication
•
•
•
•
By 1953 North and Central America had beaten it
1953 Europe
1975 eliminated in Asia
Last occurring case recorded in Merca Somalia on
October 26, 1977
• December 9, 1979, the Global Commission
certified that eradication was achieved.
• An estimation of U.S. $300 million over 11 year
period was spent.
Concept of vaccination
and Types of Vaccine
• To stimulate the immune
response without
subjecting an individual to
the risk of actual infection.
• Primarily to prevent
infection
• Strengthen an immune
response that is
inadequate, particularly in
chronic recurrent diseases
•
•
•
•
• Types of vaccines
live attenuated
vaccine
Inactivated vaccine
Polysaccharide
vaccines
Recombinant vaccines
General principles
• Another way to produce active immunity is by vaccination.
• Vaccines interact with the immune system and often
produce an immune response similar to that produced by
the natural infection
• do not subject the recipient to the disease and its potential
complications.
• Vaccines produce immunologic memory similar to that
acquired by having the natural disease.
• Many factors may influence the immune response to
vaccination.These include the presence of maternal
antibody, nature and dose of antigen, route of
administration, and the presence of adjuvants
Principles according to type.
1. Live Attenuated Vaccines
• Live vaccines are derived from “wild,” or disease-causing,
virus or bacteria. These wild viruses or bacteria are
attenuated, or weakened, in a laboratory, usually by
repeated culturing
• In order to produce an immune response, live attenuated
vaccines must replicate (grow) in the vaccinated person. A
relatively small dose of virus or bacteria is given, which
replicates in the body and creates enough virus to stimulate
an immune response.
• The immune response to a live attenuated vaccine is
virtually identical to that produced by a natural infection
2. Inactivated vaccines
• These vaccines are produced by growing the bacteria or
virus in culture media then inactivating it with heat and/or
chemicals (usually in formalin).
• Inactivated vaccines are not alive and cannot replicate. The
entire dose of antigen is administered in the injection.
These vaccines cannot cause disease from infection, even
in an immunodeficient person
• In general, the first dose does not produce protective
immunity, but only “primes” the immune system. A
protective immune response develops after the second or
third dose
• the immune response to an inactivated vaccine is mostly
humoral. Little or no cellular immunity results.
3. Polysaccharide vaccines
• are a unique type of inactivated subunit vaccine
composed of long chains of sugar molecules that
make up the surface capsule of certain bacteria
• The immune response to a pure polysaccharide
vaccine is typically T-cell independent, which
means that these vaccines are able to stimulate Bcells without the assistance of T-helper cells.
Practices
• Simultaneous administration
of antibody (in the form of
immune
globulin)
and
vaccine is introduced as
Post exposure prophylaxis of
certain diseases, such as
hepatitis
B,rabies,
and
tetanus.
• If the live vaccine is given
first, the antibody is given at
least 2 weeks after.
• Oral typhoid is not licensed
for children less than 6 years
of age
• Live parenteral (injected)
vaccines (MMR, varicella,
and yellow fever) that are not
administered simultaneously
are separated by at least 4
weeks
• If the antibody is given
before a dose of varicella
vaccine, Antibody is allowed
to degrade before giving the
vaccine to reduce the
chance of interference by the
antibody
• Simultaneous administration
of all vaccines for which a
child is eligible is very
important
in
childhood
vaccination programs, it
increases the probability that
a
child
will
be
fully
immunized at the appropriate
age
Vaccine Update
• Under-used vaccines
– Haemophilus influenzae
type b
• By end of 2002, 100% of
countries were using the
vaccine in routine
immunization programme
– Hepatitis B
• By 2001 only 75% of
countries have this vaccine
in their infant
immunization routine
– Yellow fever
• Avialable since 1937
but its used has been a
public health failure.
Over the past 2 decades
there were 12 times as
many cases as during
the previous 2 decades
– Rubella
• Universal rubella
immunization has not
been recommended by
WHO to date
Vaccine Update
• Eradication of vaccine
preventable diseases
– Polio
• Polio-free
– 1994 Americas
– 2000 western
pacific
– 2002 Europe
– Measles
• Still in progress
• In 2001 over 100
million children
have been
vaccinated in Africa
alone
– Neonatal tetanus
• 104 out of 106
developing countries
have succeeded.
• WHO, UNICEF and
UNFPA set a joint effort
to eliminate this disease
by the end of 2005
Vaccine Update
• Priority new vaccines
– HIV/AIDS
• No effective
vaccine at present
– Malaria
• No effective
vaccine at present
– Tuberculosis
• Limited protection,
immunity is
believed to wane
during adolescence
– Pneumococcal disease
– New vaccine was
licenced in 2000
United states. but not
applicable foe
developing countries
due a different
bacterial strain.
– Meningococcal disease
• New licensed in 1999
for a serogroup C
disease
– Rotavirus diarrhoea
• Development and
testing going on
Vaccine Update
• Neglected vaccines
– Cholera
• Safe and effective are
available, but oral
vaccine are under
consideration for public
health use in emergency
situation to immunize
population at high risk.
– Shigella dysentery
• It is likely to be 5-10
years before a vaccine
is introduced.
– Dengue
• 2 vaccines are
undergoing trials 1
being developed in the
United States the other
in Thailand
– Japanese encephalitis
• A vaccine has been
developed and tested in
china but not yet
suitable for global use.
– Leishmaniasis
• Development remains
fragmented and lacks
support
– Schistosomiasis
• Two leading candidates
have been successful in
animals 1 has advanced
to human trials.
Vaccine Update
• Other vaccines
– Cervical cancer
• The most advanced
candidates in
development are
recombinant protein
vaccine against HPV
types 16 and 18. Which
could prevent 50-60%
of cervical cancer.
– Respiratory syncytial virus
• Current vaccine efforts
are directed toward the
development of a
vaccine that
incorporates the 2 RSV
serotypes [A and B]
– Herpes simplex virus type 2
– Enterotoxigenic Escherichia
coli [ETEC]
• A new vaccine delivery
technologytranscutaneous
immunization involving
the use of patch to
deliver vaccine through
skin, has been
successfully tested in
humans for ETEC
vaccine