Overview of vaccine and vaccination, types of vaccines with examples, vaccine production technique, adverse effects of vaccination, precautions Email: jeevan@smail.nchu.edu.tw

1. By:
Jeevan Shrestha
Tribhuvan University
Kirtipur, Kathmandu,
Nepal.
VACCINOLOGY

2. The word vaccination was first used by Edward Jenner in
1796
The first known use of cowpox vaccine was in 1771 by an
unnamed person in England
Vaccination (Latin: vacca—cow) is so named because the
first vaccine was derived from a virus affecting cows—
the relatively benign cowpox virus
Evidence suggestive of Variolation was found in Ariyan
litrature of 1000 yrs back.

3. The earliest documented examples of variolation are
from India and China in the 17th century, where
innoculation with powdered scabs from people
infected with smallpox was used to protect against the
disease.
The process then spread to east Asia, England and
finally to America in the 18th century
Louis Pasteur created the first vaccine for rabies and
anthrax.
Maurice Hilleman was the most prolific of inventors of
vaccines. He developed successful vaccines for
measles, mumps, hepatitis A, hepatitis B, chickenpox,
meningitis, pneumonia and Haemophilus influenzae
bacteria

4. 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”.
Definition of Vaccine according to WHO
A vaccine is a biological preparation that improves immunity to a particular
disease. A vaccine typically contains an agent that resembles a
disease-causing microorganism, and is often made from weakened or killed
forms of the microbe, its toxins or one of its surface proteins. The agent
stimulates the body's immune system to recognize the agent as foreign,
destroy it, and "remember" it, so that the immune system can more easily
recognize and destroy any of these microorganisms that it later encounters.

5. Live vaccines
Attenuated live vaccines
Inactivated (killed vaccines)
Toxoids
Polysaccharide and polypeptide
(cellular fraction) vaccines
Surface antigen (recombinant)
vaccines.

6. 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.

7. 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:
Leukemia and lymphoma
Other malignancies
Receiving corticosteroids and anti-metabolic
agents
Radiation
pregnancy

8. 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.
 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.
Toxoids

9. 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.
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.
Surface antigen (recombinant)
vaccines.

10. Types of vaccines
Live
vaccines
Live
Attenuate
d
vaccines
Killed
Inactivated
vaccines
Toxoids Cellular
fraction
vaccines
Recombinan
t vaccines
•Small pox
variola
vaccine
•BCG
•Typhoid
oral
•Plague
•Oral polio
•Yellow
fever
•Measles
•Mumps
•Rubella
•Intranasal
Influenza
•Typhus
•Typhoid
•Cholera
•Pertussis
•Plague
•Rabies
•Salk polio
•Intra-
muscular
influenza
•Japanise
encephalitis
•Diphtheria
•Tetanus
•Meningococcal
polysaccharide
vaccine
•Pneumococcal
polysaccharide
vaccine
•Hepatitis B
polypeptide
vaccine
•Hepatitis B
vaccine

11.  Route of Adminstration
 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)
 Level 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.

12. 12
virus
(production
seed)
Cell culture Harvest Bulk Purification
FormulationFillingLabelingPackaging





Add

Inoculation
cell
Adjuvant Stabilizer
Bulking agent
Preservative
Inspection

centrifugation
filtering

14. After incubation the
egg white contains
millions of vaccine
viruses which are
harvested and then
separated from the egg
white.
Vaccine virus
multiplied
Virus is spun
to separate it
from the egg
white
Vaccine
virus
The vaccine virus is
injected into a 9 to
12 day old fertilized
egg and incubated
for 2 to 3
days.(during this time
the virus multiplies)

15. Standard manufacture uses a bacterial or viral antigen, e.g.
bacterium or virus, which may be killed or may be living but
attenuated.
To make a live attenuated vaccine, the disease-causing organism is
grown under special laboratory conditions that cause it to lose its
virulence or disease-causing properties.
The attenuation can be obtained by heat or by passage of the virus
in foreign host such as embryonated eggs or tissue culture cells.
Cell cultures are required for viral vaccines since viruses can
replicate only inside the living cells.
For example To produce the Sabin polio vaccine, attenuation was
only achieved with high inocula and rapid passage in primary
monkey kidney cells.

16. Inactivated vaccines are produced by killing the disease-causing
microorganism with chemicals or heat.
Vaccines are currently produced by gene techniques, i.e. instead
of using a virus or bacterium, A single gene (usually a surface
glycoprotein of the virus) can be expressed in a foreign host by
Cloning. (Expression vectors are used to make large amounts of
antigen to be used as a vaccine. Most used vectors for expression
are Bacteria: Escherichia coli, Yeasts ,Baculovirus.)
This process induces the vector to produce an antigen, which is
then purified.
The purified antigen, when combined with an adjuvant results in a
safe and very effective vaccine.
Example: Gardasil, an anti-human papilloma virus vaccine that is
very effective in preventing cervical cancer. The current Hepatitis B
vaccine is also this type.

17. Pathogen(Seed or Clinical
isolate)
Culture Attenuation Cloning,GMO
Ag
Purification
Inactivati
on
VACCINE
Seed(Live
attenuated)
Culture
VACCINE
Seed
Culture
VACCINE
Inactivation
VACCINE
Purification
VACCINE
wP,
HAV
Rab,
Flu
MMR,OPV HBV,HPVaP

18. SELECTING THE STRAINS FOR VACCINE
PRODUCTION
GROWING THE MICRO-ORGANISMS
ISOLATION & PURIFICATION OF
MICROORGANISM
INACTIVATION OF ORGANISM
FORMULATION OF VACCINE
QUALITY CONTROLAND LOT RELEASE
Upstream
processing
Downstream
processing

20. The world's first immunization campaign: the Spanish Smallpox
Vaccine Expedition, 1803-1813.
The first vaccine-preventable disease targeted for eradication was
smallpox. The last naturally occurring case of smallpox occurred
in Somalia in 1977. Next is polio and then measles.
According to United Nations Children’s Fund12 (UNICEF) vaccine
preventable diseases (VPDs) cause an estimated 2 million deaths or
more every year, of which approximately 1.5 million deaths occur
among children below five year age.
The immunisation programme in India was flagged off in 1978
as Expanded Programme on Immunisation (EPI). It gained
impetus in 1985 as the Universal Immunisation Programme
(UIP) and was carried out in phased manner to cover all districts
in the country by 1989-90

25. If the mother is known to be HBsAg negative, HB vaccine can be gi
en along with DTP at 6, 10, 14 weeks/ 6 months. If the mother's
HBsAg status is not known, it is advisable to start vaccination
soon after birth to prevent perinatal transmission of the disease. If
the mother is HBsAg positive (and especially HBeAg positive), the
baby should be given Hepatitis B Immune Globulin (HBIG) within
24 hours of birth, along with HB vaccine.
Combination vaccines can be used to decrease the number of
pricks being given to the baby and to decrease the number of
clinic visits.
Under special circumstances (e.g. epidemics), measles vaccine
may be given earlier than 9 months followed by MMR at 12-15
months.
We should continue to use OPV till we achieve polio eradication in
Nepal. IPV can be used additionally for individual protection.

26. No immune response is entirely free from the risk of
adverse reactions or remote squeal. Vaccines are not
100% effective. They are a tool to use in conjunction
with other disease control tools. The adverse
reactions that may occur may be grouped under the
following heads:
1. Reactions inherent to inoculation
2. Reactions due to faulty techniques
3. Reactions due to hypersensitivity
4. Neurological involvement
5. Provocative reactions
6. Others

27.  1. Reactions inherent to inoculation:
These may be local general reactions. The local
reactions may be pain, swelling, redness,
tenderness and development of a small nodule or
sterile abscess at the site of injection.
 The general reactions may be fever, malaise,
headache and other constitutional symptoms. Most
killed bacterial vaccines (e.g., typhoid) cause some
local and general reactions. Diphtheria and tetanus
toxoids and live polio vaccine cause little reaction.

28.  2. Reactions due to faulty techniques:
Faulty techniques may relate to
 faulty production of vaccine (e.g. inadequate inactivation of
the microbe, inadequate detoxication),
 too much vaccine given in one dose,
 improper immunization site or route,
 vaccine reconstituted with incorrect diluents,
 wrong amount of diluent used,
 drug substituted for vaccine or diluent,
 vaccine prepared incorrectly for use (e.g., an adsorbed
vaccine not shaken properly before use),
 vaccine or dliluent contaminated,
 vaccine stored incorrectly,
 contraindications ignored (e.g. a child who experienced a
severe reaction after a previous dose of DPT vaccine is
immunized with he same vaccine),
 reconstituted vaccine of one session of immunization used
again at the subsequent session.

29.  3. Reactions due to hypersensitivity:
 Administration of antiserum (e.g., ATS) may
occasionally give rise to anaphylactic shock and
serum sickness. Many viral vaccines contain traces
of various antibiotics used in their preparation and
some individuals may be sensitive to the antibiotic
which it contains. Anaphylactic shock is a rare but
dangerous complication of injection of antiserum.
There is bronchospasm, dyspnoea, pallor,
hypotension and collapse.
 The symptoms may appear within a few minutes of
injection or may be delayed up to 2 hours. Some
viral vaccines prepared from embryonated eggs
(e.g., influenza) may bring about generalized
anaphylactic reactions. Serum sickness is
characterized by symptoms such as fever, rash,
edema and joint pains occurring 7 -12 days of
injection of antiserum.

30.  4. Neurological involvement:
 Neuritic manifestations may be seen after the
administration of serum or vaccine. The well-
known examples are the postvaccinial encephalitis
and encephalopathy following administration of
anti -rabies and smallpox vaccines.

 GuillainBarre syndrome in association with the
swine influenza vaccine is another example.

31.  5. Provocative reactions:
Occasionally following immunization there may occur a
disease totally unconnected with the immunizing agent (e.g.,
provocative polio after DPT or DT administration against
diphtheria).
 The mechanism seems to be that the individual is harboring
the infectious agent and the administration of the vaccine
shortens the incubation period and produces the disease or
what may have been otherwise only a latent infection is
converted into a clinical attack.
 6. Others:
 These may comprise damage to the fetus (e.g., with rubella
vaccination); displacement in the age-distribution of a
disease (e.g., a potential problem in mass vaccination against
measles, rubella and mumps).

32. The risk of adverse reactions can be reduced by
proper sterilization of syringes and needles, by proper
selection of the subject and the product, and if due
care is exercised in carrying out the procedure.
Measles and BCG vaccines should be reconstituted only
with the diluent supplied by the manufacturer.
Reconstituted vaccine should be discarded at the end
of each immunization session and NEVER retained for
use in subsequent sessions. In the refrigerator of the
immunization centre, no other drug and substances
should be stored beside vaccines.
Training of immunization worker and their close
supervision to ensure that proper procedures are being
followed are essential to prevent complications and
deaths following immunization.