You are on page 1of 70

IMMUNIZATION

Maria Margarita Maiquez-Lota, MD,


DPPS
Department of Medical
Microbiology

Definition

Immunization

Vaccination

Herd immunity

process of inducing
immunity artificially by
vaccination or
administration of antibody
administration of any
vaccine or toxoid for
prevention of disease
resistance of a population
to infection and spread of
an infectious organism due
to the immunity of a high
percentage of the
population

Immunity
ability of the body to tolerate the
presence of material indigenous to the
body and eliminate foreign material
provides protection from infectious
diseases
indicated by the presence of antibody
very specific to a single antigen

Immune System
Defends the body
from invading
organism
Innate Immunity
first line of defense
active immediately

Acquired Immunity
protection develops
against certain types
of microbes and
foreign substances

Naturally Acquired
Passive Immunity
natural transfer of
antibodies from the
mother to the infant
transplacental
transfer
i.e. mother developed
immunity against
rubella, polio,
chickenpox can
temporarily
protection to the
infant

Artificially Acquired
Passive Immunity

introduction of antibody
may come from animal
or person who is
immune to a particular
disease
Immune serum globulin
or gamma globulin
confers immediate
protection
immediate, short lived
body do not produce
antibody

Artificially Acquired
Active Immunity

achieved by
vaccination

inactivated toxins,
killed
microorganisms, live
but attenuated, parts
of microorganism

do not cause disease


but are able to
stimulate immune
response

Naturally Acquired
Active Immunity

exposure to antigen in
the course of daily life
maybe lifelong for
some diseases

may lasts only for a


few years

i.e. chicken pox,


measles

gastrointestinal
diseases

subclinical infection
can confer immunity

History

6th century China


- drying and grinding
of small pox scabs
10th century
inoculation of smallpox
dried pus into healthy
persons
1721 Lady Mary
Montagu
- variolation in
England

History
1796 Edward
Jenner

- founder of
immunology
- first effective
vaccine
- cowpox cross
protection against
smallpox

1885 - Louis Pasteur

developed the first


attenuated vaccine against rabies virus
used virus from a rabid
dog and injected it into the
brain of rabbits
serial infection in rabbits
led to a virus strain that
was more virulent in the
rabbit but was less so in
dogs
Pasteur successfully
treated a boy (Joseph
Meister) bitten by a rabid
dog

What are the Immunizing


Agents?

Vaccine
- proteins, polysaccharides or nucleic acids
- delivered to the immune system to induce
specific responses that inactivate, destroy or
suppress the pathogen

Toxoid
- modified bacterial toxin made nontoxic
but retains the capacity to stimulate the
formation of antibody

What are the Immunizing


Agents?
Immune globulin

- antibody-containing solution from human


blood
- used for the maintenance of immunity of
immunodeficient persons
- intramuscular or intravenous
preparations
Antitoxin
- antibody derived from serum of humans or
animals after stimulation with specific
antigens

Principles of Immunization
- Considerations:
- antigen selection
- effectiveness
- ease in administration
- safety and cost
- prevention and control

Types of Immunization:
Active Immunization
- individual's own immune system is
induced to produce a specific immune
response against an antigen/pathogen
- occurs in 2 ways
upon infection or disease
artificially upon vaccination
- administering antigen to a live host
- expose to an antigenic material but not
pathogenic

Active Immunization
stimulating the immune system to produce
antibodies and cellular immune response
long lasting
requires time (days, weeks) before a
functional immune response develops

Vaccination
Is artificially acquired active immunity
reduced the prevalence and impact of
many infectious diseases
Goal:
prime humoral and cellular immune
responses against pathogens (or their
toxins) without simultaneously causing
disease

Principles of Vaccination
General Rule

The more similar a vaccine is to the


natural disease, the better the
immune response to the vaccine.

How do vaccines work?

Classification of Vaccine
1. Live Attenuated Vaccine

result in infection but not disease

Involves any process than substantially


lessens or negates the virulence of bacteria
or virus

Methods: modifying the growth condition or


manipulating microbial genes

reproduce in recipient
- Ex. BCG, Measles, Varicella, MMR, Rotavirus

Live Attenuated Vaccine


Adv. a. mimic an actual infection
b. long lasting immunity
c. fewer doses and boosters
Dis

a. requires special storage facilities


b. can be transmitted
c. can mutate back to virulent
strain

Live Attenuated Vaccine

Attenuation Methods

long term cultivation


selection of mutant strains that grow at colder
temperature
passage of the microbe through unnatural
hosts or tissue culture
removal of virulence genes

Killed Inactivated Vaccine


- killed and cannot replicate
- minimal interference from
circulating antibody
- requires boosters
- immune response mostly humoral
- antibody titer falls over time

Types of Inactivated Vaccine


1. Whole-Agent Vaccine
- contain whole, nonvirulent
microorganisms
- very effective immunogens
- larger dose and more boosters
- treat with formalin, radiation or other
agents
Ex. Pertussis, Typhoid fever, Cholera, Salk Polio,
Rabies, Influenza, Hepatitis A

Types of Inactivated Vaccine


2. Fractional
Subunit / Subcellular Vaccines
- contain some part or product of
microorganisms that can induce an immune
response
- Methods: recombinant DNA technology
: chemical synthesis
ex. Subunit: Hepatitis B, Influenza
Subcellular: Acellular pertussis, Typhoid Vi

Toxoid
- special type
of vaccine
- purified
bacterial exotoxin
that has been
denatured
- elicits
production of
antitoxins that
can neutralize the
natural toxin
- Ex.
Diphtheria and
tetanus toxoid

Cont. Subcellular vaccine

- Polysaccharide Vaccine
Pure polysaccharide
pneumococcal
meningococcal
H. influenza type b
Conjugate polysaccharide
Haemophilus influenzae type b
pneumococcal

Pure Polysaccharide
Vaccines
Not consistently immunogenic in
children <2 years of age
No booster response
Antibody with less functional activity
Immunogenicity improved by
conjugation

Conjugate vaccine enhance


immunogenicity of polysaccharide
vaccine
T cell can only recognize peptide
epitopes bound to MHC II molecules
protein conjugate added in the
vaccine is degraded into peptides and
bound to MHC II molecules by APC
leading T cell activation
cytokines produced activate sensitized B
cells

Types of Inactivated Vaccine


3. Recombinant vaccine
- contains only part of a microorganism

only those parts that induce a good immune


response

- isolation of a gene for antigenicity from


the pathogen and inserting into a plasmid vector
and cloning into a host
- uses genetic engineering
- Trojan horse vaccine
- Ex. Hepatitis B vaccine

New Vaccine Strategies

DNA vaccines
- microbial DNA is inserted into a plasmid vector and
inoculated into a recipient
- proteins produced will express microbial DNA
stimulate the immune system

and

- Adv: small amount of foreign antigen needed


to
produce effective immunity
: any potential microbial protein can be expressed
improving stimulation of antibody and CMI

New Vaccine Strategies


Anti idiotype vaccine
- based on the principle that antigen
binding region or idiotype of a given antibody
(A) can be antigenic to a genetically different
recipient and cause that recipients immune
system to produce antibodies, anti idiotype
antibodies, specific for the variable region on
antibody A

.ADV: display an identical configuration as the desired


antigen and can be used in vaccines to avoid giving
microbial antigens and reduce the potential for dangerous
side effects

Summary of Vaccine Types


A. Whole Cell Vaccine

B. Subcellular or SubunitVaccine

C. Recombinant Vaccine

Comparison Of Killed and Live Attenuated


Vaccine
Characteristic

Live, Attenuated

Killed, Inactivated

Production

Selection of
avirulent
organism

Use of chemicals
or irradiation

Booster
requirement

Usually, single
dose

Multiple boosters

Relative stability

Less stable

More stable

Type of immunity
induced

Humoral and cell


mediated
immunity

Mainly humoral
immunity

Reversion
tendency

May revert to
virulent strain

Cannot revert to
virulent strain

Boosters
involves revaccination by the same
vaccine or against the same organisms
Reasons
To assure that the immune response induced by an
at least partially successful vaccination is boosted
to a sufficiently large immune response to be
effective in protecting against disease
To assure that all recipients of the vaccination
display at least some immune response (e.g., oral
polio vaccine)
To replenish the immune response after a long
period (e.g., 10 years as is the case for tetanus
vaccine)

Vaccine in General Use


Disease

Vaccine

Remarks

Tetanus

toxoid

3 doses plus
booster

Diphtheria

toxoid

Tetanus
boosted every
10 years

Pertussis

Killed whole,
acellular

Polio

Killed ( Salk) or
Attenuated ( Sabin)

Measles

Attenuated

Mumps

Attenuated

Rubella

Attenuated

Hemophilus

Conjugated
polysaccharide

Given as MMR

3 doses plus
booster

Passive Immunization
- providing temporary protection
through administration of
exogenously produced antibody
- use of preformed antibodies from
animal or human sources
- intramuscular ex. Rabies
- intravenous ex. Hepatitis B

Passive Immunization
results when antibodies are produced by
one individual and then acquired by another
Naturally acquired
Acquisition of the antibodies in colostrum by an infant
crossing of the placenta by maternal antibodies

artificially acquired
antiserum or antibodies produced by one individual are
transfused into a second individual

last for at most months since antibodies


functional immediately upon reception,

Types of Passive
Immunization

Immune serum globulin ( ISG)


- immunoglobulin extracted from pooled blood of
at least 1000 human donors
- concentrates antibody content to increase
potency and eliminates potential pathogens
- IM route
- protection 2 to 3 months
- Uses: treatment of choice for hepatitis A and
measles
: replacing antibodies in immunodeficient
patients

Types of Passive
Immunization
Specific Immune globulin ( SIG )
- more defined donor group
- collect serum from patients in
convalescence or in hyperimmune state
- Adv: contain higher titers of specific
antibodies from smaller pool of
patients
- Dis: limited availability

Types of Passive
Immunization
Antisera and antitoxin
- from animal origin
Ex. Horses antisera for diphtheria, botulism
and spider/snakes bites

- used when human immune globulin


is not available
- more prone to allergic reaction
Serum sickness or anaphylaxis

Agents and Indication of Passive Immunization


Disease

Agent

Indication

Black Widow Spider


Bite

Horse antitoxin

Post exposure

Botulism

Horse antitoxin

Post exposure

Diphtheria

Horse antitoxin

Prophylaxis, treatment

Hepatitis A

Pooled human IgG

Post exposure

Hepatitis B

Pooled human IgG

Post exposure (plus vaccine)

Measles

Pooled human IgG

Post exposure

Rabies

Pooled human IgG

Post exposure (plus vaccine)

Snake Bite

Horse antivenin

Post exposure

Tetanus

Pooled human IgG


Or horse antitoxin

Prophylaxis, treatment

What is an adjuvant ?
- compound that enhances immunogenicity
- prolongs antigen retention at injection site
- Ex: aluminum hydroxide salts
calcium phosphate
Freunds adjuvant
- emulsion of mineral oil and extracts of
mycobacteria
beeswax

Timing and Spacing


Antibody and Live Vaccines
Product given first

Action

Vaccine

2 weeks before giving


the antibody

Antibody
( blood / blood product,
immunoglobulin)

> 3 months before


giving the vaccine

Timing and Spacing


Can you give simultaneous administration of
any vaccine?

Spacing of vaccine combinations not


given simultaneously
Combination

Minimum interval

Two live injected

4 weeks

All other

none

Adverse Effects
Common
local allergic reaction
- pain, swelling, redness at the site of
injection

systemic
- fever, headache, malaise

Rare
panencephalitis, back mutation to virulent
strain, convulsions

Live Vaccine: Contraindicated or Not


Contraindicated?
Encephalopathy
Fever, cough and
colds
immunosuppression
TB patient
allergies to vaccine
component

Pregnancy
breastfeeding
prematurity
mild diarrhea
recent blood
transfusion

Contraindications and
Precautions
Condition

Live

Inactivated

Allergy to vaccine component

Encephalopathy

Pregnancy

Immunosuppression

Severe illness

Recent blood product

C contraindication

P Precaution

V vaccinate if indicated

Invalid Contraindication
mild illness
disease exposure or convalescence
antibiotic therapy
pregnancy in the household
breastfeeding
premature birth
family history unrelated to immunosuppression
Need for TB skin testing
need fpr multiple vaccines
minor illness
mild diarrhea

Determinants of Immune
Response
- immune response to specific antigen is
genetically determined
1.
2.
3.
4.

chemical and physical state of the antigen


mode of administration
catabolic rate of the antigen
host factors

Immune Response to Vaccine


Antigen

Immune Response to Vaccine


Antigen
Primary Response
- latent period
- antibody detected 7-10 days
- early - IgM
late IgG
Oral Live virus vaccine
ex. Oral Polio Vaccine
- replicate at mucosal surface
- induce sIgA at respiratory tract, GIT

Immune Response to Vaccine


Antigen
Secondary response
- heightened humoral and cell mediated
immune response
- occur rapidly at 4-5 days
- due to immunologic memory mediated by T
and B lymphocytes
T independent antigen
- i.e. polysaccharides
- do not evoke 20 response

OPV vs IPV

General Principles for Vaccine


Scheduling
Optimal response to a vaccine depends on
nature of the vaccine
age
immune status

Recommendations for the age at which vaccines


are administered are influenced by
age-specific risks for disease
age-specific risks for complications
ability of persons of a certain age to respond to the
vaccine
potential interference with the immune response by
passively transferred maternal antibody

General Principles for Vaccine


Scheduling
inactivated vaccines, toxoids, recombinant
subunit and polysaccharide conjugate vaccines
require administering >2 doses
Tetanus and diphtheria toxoids require booster doses

Unconjugated polysaccharide vaccines


do not induce T-cell memory, and booster doses are
not expected to produce substantially increased
protection

General Principles for Vaccine


Scheduling
live attenuated virus vaccines
stimulate both cell-mediated immunity
and neutralizing antibodies
usually can induce prolonged, often
lifelong immunity, even if antibody titers
decline as time progresses
Subsequent exposure to infection
usually does not lead to viremia but to a
rapid anamnestic antibody response.

Live Vaccines and


Booster Dose
Approximately 90%--95% of recipients of a single dose
live vaccine at the recommended age, develop
protective antibody within 2 weeks of the dose
a second dose is recommended to provide another
opportunity to develop immunity
Ex: MMR

approximately 20% of persons aged >13 years fail to


respond to the first dose of varicella vaccine
99% of recipients seroconvert after two doses

The Expanded Programme on


Immunization (EPI)
WHO laucnched the Expanded Programme on
Immunization in 1974
six diseases chosen were tuberculosis, diphtheria,
neonatal tetanus, whooping cough, poliomyelitis and
measles

Selection was based on


high burden of disease
Availability of a well-tried vaccines at an affordable price

"Expanded" also meant increased coverage less than 5% of children in developing countries were
being reached

The Expanded Programme on


Immunization (EPI)
program developed
training materials and
disseminated widely
countries in the world
adopted the principle of a
national immunization
program

training courses were


conducted

Every community
was reached by
some form of
immunization
service
number of vaccine
preventable
diseases decreased
in most countries

Vaccines Used in the Expanded


Program on Immunization (EPI) since
1974

BCG
Polio
DPT
Measles
Yellow fever ( endemic )
Hepatitis B

What diseases are


included in the EPI in the
Philippines?

Expanded Program on
Immunization
immunization increased from 5 % to 80 %
worldwide
Vaccines against 7 diseases recommended by
EPI
1. BCG
2. DPT
3. OPV
4. measles
5. hepatitis B
6. tetanus toxoid for pregnant women

Pre and Post Vaccine Era

Measles
Case definition:
Fever, cough, runny
nose, conjunctivitis
and Koplicks spot
maculopapular rash
on face proceeding
downward and
outward

Vaccine

Minimum Age
at 1st dose

No. of
Doses

BCG

At birth

DPT

6 weeks

4 weeks

Reduces chance of
severe pertussis

OPV

6 weeks

4 weeks

Increased
protection if given
earlier

Hepatitis B At birth

4 weeks

Reduces chance of
infection and
carrier

Measles

9 months ( 6
months)

Min Interval
Bet Doses

Reason
Protects against
the possibility of
infection from
other family
members

80% of measles
can be prevented
by immunization at
this age

vaccine

Timing of Vaccination

%
duration of protection
protect

TT1

5th - 6th month of


pregnancy

TT2

at least 4 weeks after TT1

80

Protects from neonatal


tetanus
3 yrs protection

TT3

At the 5th - 6th month of


succeeding pregnancy
regardless f interval

85

Protects from neonatal


tetanus
5 yrs protection

TT4

At the 5th - 6th month of


succeeding pregnancy
regardless f interval

99

Protects from neonatal


tetanus
10 yrs protection

TT5

At the 5th - 6th month of


succeeding pregnancy
regardless f interval

99

Lifetime protection
All infants born will be
protected

CDC MMWR Weekly,October 13, 2006 / 55(40);Q1-Q4

United States; Jan. 5, 2007; Centers for Disease Control