LECTURE – 9

IMMUNIZING AGENTS

Ms Rubab Zulfiqar
Lecturer
NUMS Department of Public Health
 IMMUNIZING AGENTS
The immunizing agents may be classified as:
• vaccines
• immunoglobulins
• antisera.
VACCINES
 VACCINES
• “Vaccine is an immuno-biological substance designed to
produce specific protection against a given disease. It
stimulates the production of protective antibody and other
immune mechanisms”
 VACCINES
• vaccination has been the most effective medical strategy to
control infectious diseases
• Smallpox has been eradicated world-wide and poliomyelitis has
been almost eradicated
• Vaccination is estimated to save at least 2-3 million lives every
year
• Vaccines may be prepared from
live modified organisms,
inactivated or killed organisms,
 extracted cellular fractions,
toxoids or combination of these.
TYPES
• Live Vaccines
• Killed Vaccines
• Subunit Vaccines
• Combination Vaccines
LIVE VACCINES
• Live vaccines are prepared from live or wild (generally attenuated)
organisms.
• These organisms have been passed repeatedly in the laboratory in
tissue culture or chick embryos and have lost their capacity to
induce full-blown disease but retain their immunogenicity
• E.g., BCG, measles, oral polio
Live vaccines are more potent immunizing agents than killed
vaccines:
live organisms multiply in the host and the resulting antigenic
dose is larger than what is injected
 live vaccines have all the major and minor antigenic
components
live vaccines engage certain tissues of the body, as for example,
intestinal mucosa by the oral polio vaccine
 There may be other mechanisms such as the persistence of
latent virus
CONTRAINDICATIONS
• Immunosuppressed persons: AIDS, leukemia, lymphoma
or malignancy or because of therapy with corticosteroids,
alkylating agents, antimetabolic agents, or radiation.
• Pregnant women
• DOSE:
single dose of vaccine.
If two live vaccines are required they should be given either
simultaneously at different sites or with an interval of atleast 3 weeks.
E.g., 95 to 98 per cent of recipient will respond to single dose of measles
vaccine. The second dose is given to ensure that 100 per cent of persons are
immune.
The other exception is polio vaccine which needs three or more doses to be
given at spaced intervals to produce effective immunity.

• Produces durable immunity, but not as long as that of the natural

infection
• STORAGE: properly stored to retain effectiveness.
INACTIVATED OR KILLED VACCINES
• Inactivated vaccines are produced by growing virus or bacteria in
culture media and then inactivating them with heat or chemicals
(usually formalin).
• When injected into the body they stimulate active immunity.
• Safe but generally, less efficacious than live vaccines.
E.g:
 cholera vaccine offers only 50 per cent protection.
The efficacy of 3 doses of pertussis vaccine is about 80 per cent in the first
three years, and almost "nil" 12 years after immunization.
• DOSE: Primary series of 2 or 3 doses of vaccine followed by
"booster" injections The duration of immunity following the use of
inactivated vaccines varies from months to many years.
• SITE OF ADMINISTRSTION: Subcutaneous or intramuscular
route.
• Safe for immunodeficient person.
• Not affected by circulating antibody.
• More stable than live attenuated vaccines
• CONTRAINDICATION: severe local or general reaction to a
previous dose.
Killed Vaccine vs Live Vaccine
 SUBUNIT VACCINES
Single or multiple antigenic components of a microorganism that are
capable of stimulating a specific immune response sufficient to
protect from the relevant pathogen infection or from the clinical
manifestation of the disease.

Toxoid
Protein Vaccines
Recombinant Protein Vaccines
Polysaccharide-based vaccines
Conjugated vaccines
TOXOIDS
• Certain organisms produce exotoxins, e.g., diphtheria and
tetanus bacilli.
• The toxins produced by these organisms are detoxicated
and used in the preparation of vaccines.
• The antibodies produced neutralize the toxic moiety
produced during infection.
• Highly efficacious and safe immunizing agents.
PROTEIN VACCINES
• Immunization with single protein or a combination of proteins from a
pathogen is sufficient to stimulate a protective immune response
against that particular microorganism
• Proteins can be purified from in-vitro cultures of a pathogenic
microorganism.

Acellular pertussis vaccines contain two to four different proteins purified

from B. pertussis
Influenza vaccine composed of haemagglutinin (HA) and neuraminidase
(NA) purified from the inactivated influenza virus.
RECOMBINANT PROTEIN VACCINES
• The genes encoding any immunogenic protein can be cloned and
expressed in bacterial, yeast and mammalian cells using recombinant
DNA technology.
• The first such recombinant antigen vaccine for human use is the
Hepatitis B vaccine
• Hepatitis B vaccine is made by cloning the gene for major surface
antigen (HBsAg) in a yeast cell.
• Modified yeast cell produces large amounts of hepatitis B surface
antigen, which is purified and harvested and used to produce the
vaccine.
• Cleaner vaccine preparation with better safety profiles
• A drawback of vaccine preparation containing pure recombinant
protein(s) is their reduced immunogenicity that may require the
addition of an adjuvant to achieve enhanced efficacy
POLYSACCHARIDE-BASED VACCINES
• Prepared from extracted cellular fractions
• The surface of many pathogenic bacteria is covered by a capsular shell
that is mainly assembled from polymeric glycans.
• Stimulation of an antibody response against the surface polysaccharide
of pathogenic bacteria
• Immune responses are serotype specific.
• E.g: meningococcal vaccine from the polysaccharide antigen of the cell
wall (MenACWY)
 CONJUGATED VACCINES
• Polysaccharides are poor in activating B cells to produce antibodies
in children younger than 2 years of age.
• If these polysaccharide antigens are chemically linked (conjugated)
to a protein that T-cells recognize, then these conjugate vaccines can
elicit strong immune responses
• sero-type specific (multivalent formulations)
• Pneumococcal conjugate vaccines (PCVs) target several serotypes of
S. pneumoniae and have significantly reduced the incidence of
pneumococcal diseases such as pneumonia, meningitis, and otitis
media in children and adults.
 COMBINATIONS
• If more than one kind of immunizing agent is included in the
vaccine, then it is called a combined or mixed vaccine.
• Does not increase the risk of adverse reactions

E.g:
DPT (Diphtheria-pertussis-tetanus)
DPT-Hep B-Hib (Diphtheria, pertussis, tetanus, hepatitis B and
haemophilus influenza type B).
MMR (Measles, mumps and rubella)
ADVANTAGES
• Simplified administration
• Reduced costs
• Reduced number of visits
• Reduced storage cost
• Facilitates the addition of new vaccine into immunization
programme
VACCINE EXCEPIENTS
• Adjuvants
• Antibiotics
• Preservatives
• Stabilizers
 ADJUVANTS

• A substance is added to a vaccine to enhance the immune response by

degree and/or duration, making it possible to reduce the amount of
immunogen per dose or the total number of doses needed to achieve
immunity.
• E.g; aluminium salts (aluminium hydroxide, aluminium phosphate or
potassium aluminium sulfate) which primarily enhance the immune
response to proteins.
ANTIBIOTICS
• Antibiotics are used during the manufacturing phase to prevent
bacterial contamination of the tissue culture cells in which the
viruses are grown.
• For example, MMR vaccine and IPV each contains less than 25
micrograms of neomycin per dose.
PRESERVATIVES
• These are chemicals (e.g. thiomersal, formaldehyde) added
to killed or subunit vaccines in order to inactivate viruses,
detoxify bacterial toxins, and to prevent serious secondary
infections as a result of bacterial or fungal contamination
STABILIZERS
• To confirm product quality or stability, compounds may be added to
vaccines for a variety of manufacture-related issues
controlling acidity (pH)
 stabilizing antigens through necessary steps in the manufacturing
process, such as freeze drying
preventing antigens from adhering to the sides of glass vials with a
resultant loss in immunogenicity
• EXAMPLES: Potassium or sodium salts, lactose, human serum
albumin and a variety of animal proteins, such as gelatine and bovine
serum albumin
IMMUNOGLOBULINS
• The human immunoglobulin system is composed of 5
major classes (IgG, IgM, lgA, lgD and IgE).
• Peak blood levels are reached in 2 days after intramuscular
injection

• Immunoglobulin preparations
Normal human immunoglobulin
Specific (hyper-immune) human immunoglobulin.
NORMAL HUMAN IMMUNOGLOBULIN
SPECIFIC HUMAN IMMUNOGLOBULIN
• The specific (hyperimmune) human lg contain at least 5 times the antibody
potential of the standard preparation per unit volume.
• preparations are made from the plasma of patients who have recently
recovered from an infection or are obtained from individuals who have been
immunized against a specific infection
• High antibody content against an individual infection and provide immediate
protection
 specific human Igs are used for chickenpox prophylaxis of highly susceptible
individuals (VZIg)
 for post-exposure prophylaxis of hepatitis B (HBIg), and rabies (HRIg) and for tetanus
(HTIg) prophylaxis in the wounded
 ADVERSE REACTIONS
• Local reactions (e.g., pain, sterile abscesses) are relatively common
when large volumes are injected intramuscularly.
• Systemic reactions can be rapid or late.
Rapid reactions occur during or within minutes of administration,
and are anaphylactic in type (flushing, flank pain, rigor, dyspnoea,
and signs of shock).
 Late reactions may occur within hours or days, are usually less
severe, and may include urticaria, arthralgia, pyrexia or diarrhoea.
ANTISERA OR ANTITOXINS
• The term antiserum is applied to materials prepared in animals
• Antitoxins or specific immunoglobulins prepared from
immunized animals such as horses
• Administration of antisera may occasionally give rise to serum
sickness and anaphylactic shock due to abnormal sensitivity of
the recipient
• Anti tetanus serum (ATS) , anti diphtheria serum (ADS), Anti
snake venom, anti gas gangrene serum
COLD CHAIN
• A system of storage and transport of vaccines at low temperature
from the manufacturer to the actual vaccination site
• vaccine failure may occur due to failure to store and transport under
strict temperature controls
• 6 Rs of Supply Chain: The right vaccine in the right quantity at
the right place at the right time in the right condition (no
temperature breaks in cold chain) and at the right cost
VACCINES STORAGE
• Vaccines which must be stored in the freezer compartment: polio and
measles
• Vaccines which must be stored in the COLD PART but never allowed
to freeze are : (DPT, tetanus toxoid) hepatitis B, BCG
• vaccines (except polio) can be stored up to 5 weeks if the refrigerator
temperature is kept between 2 and 8 degrees C.
• Reconstituted BCG and measles vaccines can be kept at +2°C to +8°C
for maximum of 4 hours.
• Store the diluents, between +2° to + 8° C
COLD CHAIN EQUIPMENT
• Walk-in cold rooms (WIC) : Located at regional level store vaccines upto 3 months and
serve 4-5 districts.
• Deep freezers : Supplied to all districts (large) and PHCs (small) to store vaccines,
preparation of ice packs (-15 to -25 ° C) at PHC level
• lce-lined refrigerators (ILR) : store all UIP vaccines (+2 to +8 ° C)
• Dial thermometer : keep in the ILR to record temperature twice a day
• Cold boxes: transportation of the vaccines
• Vaccine carriers : Vaccine carriers (6-20) are used to carry small quantities of vaccines
for out of reach session
• Day carriers : Day carriers are used to carry small quantities of vaccines (6-8 vials) to a
nearby session.
• Ice packs
VACCINE VIAL MONITOR
• A VVM is a label containing a heat-sensitive material which is
placed on a vaccine vial to register cumulative heat exposure over
time.
• The combined effects of time and temperature cause the inner square
of the VVM to darken
• Inner square lighter than the outer square- use the vaccine
• Inner square darker than the outer square- Don’t use the vaccine
 ADVERSE EVENTS FOLLOWING
IMMUNIZATION (AEFI)
• An AEFI is any untoward medical occurrence which follows
immunization, and which does not necessarily have a causal
relationship with the usage of the vaccine
• The adverse event may be any unfavourable or unintended sign,
abnormal laboratory finding, symptom or disease.
• True adverse events i.e. really a result of the vaccine or immunization
process,
• coincidental events that are not due to the vaccine or immunization
process but are temporally associated with immunization
ROUTINE IMMUNIZATION
SCHEDULE OF PAKISTAN
 CLASS ASSIGNMENT
What VPDs are included in EPI?
Causative agent, mode of transmission of disease of VPDs
EPI Vaccines (Site of administration, type of vaccine)
THANK YOU