Chapter 18 Vaccines

Vaccination
chapter 18
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Active and Passive Immunization
Immunity to infectious microorganisms can be achieved by

active or passive immunization.
Immunity can be acquired either by natural processes
(usually by transfer from mother to fetus or by previous
infection by the organism) or
by artificial means such as injection of antibodies or
vaccines
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Passive immunization, in which preformed antibodies are
transferred to a recipient, occurs naturally by transfer of
maternal antibodies across the placenta to the developing fetus.
Maternal antibodies to many microorganisms like diphtheria,
tetanus, streptococci, rubella, mumps, and poliovirus all afford
passively acquired protection to the developing fetus.
Maternal antibodies present in colostrum and milk also provide
passive immunity to the infant
Passive immunization can also be achieved by injecting a

recipient with preformed antibodies.
Because passive immunization does not activate the immune
system, it generates no memory response and the protection
provided is transient
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Conditions that require the use of passive
immunization:
• Deficiency in synthesis of antibody as a result of congenital or

acquired B-cell defects, alone or together with other
immunodeficiencies.
• Exposure or likely exposure to a disease that will cause
complications or when time does not permit adequate
protection by active immunization (immunocompromised
patients exposed to microorganisms)
• Infection by pathogens whose effects may be ameliorated by
antibody. For example, if individuals who have not received
up-to-date active immunization against tetanus suffer a
puncture wound.
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Unlike passive immunization that provide transient
protection or alleviation of an existing condition, the goal of
active immunization is to elicit protective immunity and
immunologic memory.
Active immunization can be achieved by natural infection

with a microorganism, or it can be acquired artificially by
administration of a vaccine.
the immune system plays an active role—proliferation of

antigen-reactive T and B cells results in the formation of
memory cells.
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Designing Vaccines for Active
Immunization
• Several factors must be kept in mind in developing a
successful vaccine.
1. The development of an immune response does not

necessarily mean that a state of protective immunity has
been achieved.
• Which branch of the immune system is activated, vaccine
designers must recognize the important differences
between activation of the humoral and the cell-mediated
branches.
• 2. The need to develop of immunologic memory. The role
of memory cells in immunity depends, in part, on the
incubation period of the pathogen. 11
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1. Whole-Organism Vaccines
A. Attenuated Viruses and Bacteria
Microorganisms can be attenuated so that they lose their

ability to cause significant disease (pathogenicity) but retain
their capacity for transient growth within an inoculated host.
Provide prolonged immune-system exposure to the

individual epitopes on the attenuated organisms, resulting in
increased immunogenicity and production of memory cells
e.g. measles, mumps, and rubella (MMR), tuberculosis
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B. Inactivated whole Pathogenic Organisms
Inactivation of the pathogen by heat or by chemical means so

that it is no longer capable of replication in the host. It is
critically important to maintain the structure of epitopes on
surface antigens during inactivation.
Heat inactivation would denature proteins, chemical

inactivation requires the use of formaldehyde.
It elicits only humoral immune response, booster doses are

required
e.g. cholera, influenza , hepatitis A, plague
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2. Purified Macromolecules as Vaccines
A. Bacterial Polysaccharide Capsules

 The virulence of some pathogenic bacteria depends primarily
on the antiphagocytic properties of their hydrophilic
polysaccharide capsule. Coating of the capsule with antibodies
and/ or complement greatly increases the ability of
macrophages and neutrophils to phagocytose such pathogens.
These findings provide the rationale for vaccines consisting of
purified capsular polysaccharides.
Streptococcus pneumonia (pneumococcal pneumonia) and
Neisseria meningitides (meningitis).
• One limitation of polysaccharide vaccines is their inability to
activate T cells. They activate B cells in a thymus independent
H
• type 2 (TI-2). No class switching and no memory cells. 17

Haemophilus influenzae type b (Hib) vaccine
 is a conjugate vaccine that combines the polysaccharide antigen
to some sort of protein carrier
 It is more immunogenic than the polysaccharide alone, and
because it activates TH cells, it enables class switching from
IgM to IgG
 Although this type of vaccine can induce memory B cells, it
cannot induce memory T cells specific for the pathogen.
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The vaccine is prepared by conjugating the surface
polysaccharide of Hib to a protein molecule
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B. Toxoids
 Some bacterial pathogens, including those that cause,
diphtheria and tetanus vaccines, can be made by
purifying the bacterial exotoxin and then inactivating
the toxin with formaldehyde to form a toxoid.
 Vaccination with the toxoid induces anti-toxoid
antibodies, which are also capable of binding to the
toxin and neutralizing its effects.
 Large quantities of the exotoxin can be produced,
purified, and subsequently inactivated by recombinant
DNA technology. 21
C. Proteins from Pathogens Produced by Recombinant
Techniques
 Recombinant DNA technology has been used to successfully
produce vaccines for a number of genes encoding surface
antigens from viral, bacterial, and protozoan pathogens.
• The first such recombinant antigen vaccine approved for human
use is the hepatitis B vaccine.
• Cloning the gene for the major surface antigen of hepatitis B
virus (HBsAg) and expressing it in yeast cells. The yeast cells are
harvested and disrupted by high pressure, releasing the
recombinant HBsAg, which is then purified by conventional
biochemical techniques.
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Recombinant-Vector Vaccines
 Genes that encode major antigens of especially virulent
pathogens can be introduced into attenuated viruses or bacteria.
The attenuated organism serves as a vector, replicating within the
host and expressing the gene product of the pathogen.
 Vaccinia virus, the attenuated vaccine used to eradicate

smallpox, has been widely employed as a vector vaccine.
This large, complex virus, with a genome of about 200
genes, can be engineered to carry several dozen foreign
genes without impairing its capacity to infect host cells and
replicate.
• The genetically engineered vaccinia expresses high levels of
the inserted gene product, which can then serve as a potent
immunogen in an inoculated host. 23
Production of vaccinia vector vaccine.
 The gene that encodes the desired antigen is inserted into a
plasmid vector adjacent to a vaccinia promoter and flanked on
either side by the vaccinia thymidine kinase (TK) gene.
 When tissue culture cells are incubated simultaneously with
vaccinia virus and the recombinant plasmid, the antigen gene
and promoter are inserted into the vaccinia virus genome by
homologous recombination at the site of the nonessential TK
gene, resulting in a TKrecombinant virus.
 Cells containing the recombinant vaccinia virus are selected by
addition of bromodeoxyuridine (BUdr), which kills TK cells.
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DNA Vaccines
plasmid DNA encoding antigenic proteins is injected directly
into the muscle of the recipient. Muscle cells take up the DNA
and the encoded protein antigen is expressed, leading to both a
humoral antibody response and a cell-mediated response.
• The encoded protein is expressed in the host in its natural

form—there is no denaturation or modification. The immune
response is therefore directed to the antigen exactly as it is
expressed by the pathogen.
• DNA vaccines also induce both humoral and cell-mediated
immunity;
• DNA vaccines cause prolonged expression of the antigen,
which generates significant immunological memory.
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Vaccination

Immunity to infectious microorganisms can be achieved by

Passive immunization can also be achieved by injecting a

• Deficiency in synthesis of antibody as a result of congenital or

Active immunization can be achieved by natural infection

the immune system plays an active role—proliferation of

1. The development of an immune response does not

A. Attenuated Viruses and Bacteria

Microorganisms can be attenuated so that they lose their

Provide prolonged immune-system exposure to the

e.g. measles, mumps, and rubella (MMR), tuberculosis

Inactivation of the pathogen by heat or by chemical means so

Heat inactivation would denature proteins, chemical

It elicits only humoral immune response, booster doses are

A. Bacterial Polysaccharide Capsules

• type 2 (TI-2). No class switching and no memory cells. 17

 Vaccinia virus, the attenuated vaccine used to eradicate

• The encoded protein is expressed in the host in its natural

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