The document discusses different types of vaccines, including live attenuated vaccines, inactivated vaccines, subunit vaccines, recombinant vaccines, DNA vaccines, and conjugate vaccines. Live attenuated vaccines use weakened live pathogens to induce immunity, while inactivated vaccines use killed pathogens. Subunit vaccines contain purified antigens from pathogens. Recombinant vaccines produce antigens using genetic engineering, while DNA vaccines use DNA encoding antigens. Conjugate vaccines chemically link bacterial coat proteins to carrier proteins to generate stronger immune responses.

2.  It is the suspension of organisms or fraction of
organisms that is used to induce immunity.
 In vaccination, a preparation of weakened
pathogen are introduced into the body.
 Vaccines have been developed for many diseases
such as diphtheria, pertusis (whooping cough),
tetanus etc.
 Vaccines are designed with the approach,with an
examination of the ability of the vaccines to
induce humoral and cell mediated immunity and
production of memory cells.

3.  highly reliable
 Tolerable by people
 No side effects
 Specific for particular disease
 Should be safe
 Induces broad range of immune response i.e. humoral and cellular
responses
 Long lived immunity with a single doses.
 Should develop immunologic memory
 Development of temperature –sensitive mutants i.e. remain stable
without refrigeration.
 More economical
 affordable

4.  DNA vaccines
 Subunit vaccines
 Recombinant vaccines
 Viral vaccines
 Bacterial vaccines

5. 1. Recombinant antigen
vaccine
2. Recombinant vector
vaccine
3. Synthetic peptide vaccine
Recombinant vaccines

6.  DNA encoding antigenic determinants can be isolated
and cloned in bacteria,yeast,or mammalian cells.
 The first recombinant vaccine was developed
for the major antigen (VP1) of the foot and
mouth disease virus.in this case, viral RNA
encoding the VP1 surface antigen was
transcribed into cDNA was then inserted into
an E.coli plasmid and cloned in E.coli. This
procedure allowed production of large
quantities of VP1 antigen, which was then
purified and used as a vaccine in animals.
Recombinant antigen
vaccines

7.  In the same way,the first recombinant
antigen vaccine approved for human
use was the hepatitis B vaccine.
 Example : The other vaccines that are
being developed in animal models
include β subunit of cholera toxin, the
entero toxin of E. coli etc.
 Advantages: They mounted (in some cases)
a protective immune response to a
subsequent challenge with the live
pathogen.
 Disadvantages :They are processed as
exogenous antigens.

8.  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.
 A number of organism are used for vector
vaccines,including vaccinia virus.
Recombinant vector
vaccines

9.  For example: vaccinia virus is widely
employed as a vector to eradicate small
pox.
 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.

13.  Production of vaccinia vector vaccine. The gene
that encodes the desired antigen (orange) is
inserted into a plasmid vector adjacent to a
vaccinia promoter (pink) and flanked on either side
by the vaccinia thymidine kinase (TK) gene
(green). When tissueculture 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.

14.  EXPRESSES HIGH LEVELS
OF THE INSERTED GENE
PRODUCT WHICH CAN
THEN SERVE AS A
POTENT IMMUNOGEN IN
AN INOCULATED HOST.
 USE ONLY THOSE
ANTIGENIC FRAGMENTS
OF A MICROORGANISMS
BEST STIMULATE AN
IMMUNE RESPONSE.
 IN HEALTHY INDIVIDUAL,
AN ATTENUATED
VACCINE HAS ONLY
LIMITED GROWTH,BUT IN
INDIVIDUALS WITH
IMMUNODEFICIENCY,EVE
N AN ATTENUATED
VACCINE CAN BE
POTENTIALLY FATAL.SO
AS AN ALTERNATIVE
WHICH IS NOT VIRULENT
EVEN IN INDIVIDUALS
WITH SEVERE IMMUNE
SUPPRESSION,IS USED
Salmonella typhimurium.

15.  SYNTHETIC PEPTIDES THAT MIMIC THOSE
EPITOPES AND USE THE PEPTIDES AS
VACCINES.
 ADVANTAGES: EASE OF SYNTHESIS UNDER
HIGHLY CONTROLLED CONDITIONS AND
VIRTUALLY COMPLETE SAFETY.
 CHEAP, STABLE, LESS QUALITY ASSURANCE
IS REQUIRED ,NATURAL VARIATION OF THE
VIRUS CAN BE READILY ACCOMODATED.
 LESS TOXIC.

16.  DISADVANTAGES:
 Requires adjuvants.
 May be less immunogenic than conventional other
vaccines.
 It is difficult to elicit both humoral and cellular
immunity to them.
 Requires primary course of injections followed by
boosters doses.
 Without T-cell epitopes they fail to elicit cell-
mediated immunity.

17.  It includes:
1. Live ,attenuated vaccines.
2. Inactivated or killed vaccines.
 Live ,attenuated vaccines:
1. In some cases, 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.
2. There are some examples of agents that
are naturally attenuated by the virtue of
their ability to cause disease in a given host
although they can immunize the host.

18.  The first vaccine used by Jenner is of this type
vaccinia virus (cowpox) inoculations of humans .
 Attenuation can often be achieved by growing a
pathogenic bacterium or virus for prolonged periods
under abnormal culture conditions .This procedure
selects the mutants that are better suited to growth in
the abnormal culture conditions and are therefore
less capable of growth in the natural host. For
example, an attenuated strain of Mycobacterium
bovis called Bacillus Calmette-Guerin (BCG) was
developed by growing M. bovis on a medium
containing increasing concentrations of bile. After
13 years, this strain had adapted to growth in strong
bile and had become sufficiently attenuated that it
was suitable as a vaccine for tuberculosis.

19.  Because of their capacity for transient growth, such
vaccines provide prolonged immune-system exposure to
the individual epitopes on the attenuated organisms,
resulting in increased immunogenicity and production of
memory cells.
 As a consequence, these vaccines often require only a
single immunization, eliminating the need for repeated
boosters. This property is a major advantage in Third
World countries, where epidemiologic studies have
shown that roughly 20% of individuals fail to return for
each subsequent booster.
 The ability of many attenuated vaccines to replicate
within host cells makes them particularly suitable for
inducing a cell mediated response.

20.  A major disadvantage of attenuated
vaccines is the possibility that they will revert
to a virulent form.
 however, the risk of vaccine related
complications is much lower than risks from
infection.
 The low in-cidence of this side effect
compared with the rate of
encephalopathy associated with infection
argues for the efficacy of the vaccine.
 Some virus have inability to grow at the
elevated temperatures of the inner body
and is therefore limited in its range.

21.  Another common means to achieve
attenuation of vaccine is inactivation of the
pathogen by heat or chemical means so
that the pathogen raises an immune
response but is not capable of replication in
the host.
 It is important to maintain the structureof
epitopes on surface antigens during
inactivation.
 Heat inactivation is generally unsatisfactory
because it causes extensive denaturation
of proteins; thus, any epitopes that depend
on higher orders of protein structure are
likely to be altered significantly.

22.  Chemical inactivation with formaldehyde
or various alkylating agents has been
successful. The Salk polio vaccine is
produced by formaldehyde inactivation.
 Killed vaccine requires repeated boosters
to maintain the immune status of the host.
 Killed vaccine induce a predominantly
humoral antibody response; they are less
effective then attenuated.
 Large quantities of the infectious agent
must be handled prior to inactivation,and
those exposed to the process are at risk of
infection.

23.  The safety of inactivated vaccines is
greater than that of live attenuated
vaccines which retain the capability to
replicate and possibly revert to an active
form.
 Most commonly used against viral and
bacterial diseases.
 It is stable,easy to store and transport.
 The drawback to this is vaccines be
administrated by injection in mass
immunization campaigns.

24.  A vaccination strategy under investigation for
a number of diseases utilises plasmid DNA
encoding antigenic proteins, which 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.
 In this technique,the injected DNA is taken and
expressed by the host muscle cells with much
greater efficiency than in tissue culture cells.
The DNA appears either to integrate into the
chromosomal DNAor to be maintained for long
periods in an episomal form.

25.  The encoded protein is expressed in the
host in its natural form –there is no
denaturation or modifications. 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,to stimulate
both arms of the adaptive immune
response with non-DNA vaccines normally
requires immunization with a live
attenuated preparation,which introduces
additional elements of risk.

26.  Finally, DNA vaccines cause prolonged
expression of the antigen which
generates significant immunological
memory.
 Refrigeration is not required for the
handling and storage of the plasmid
DNA. This feature lowers the cost and
complexity of delivery.
 It has lower cost .

27.  In viral antigen is expressed not only by
the muscle cells but also by the dendritic
cells in the injection area.
 Only protein antigens can be encoded
and certain vaccine,such as those for
pneumococcal infections,use
polysaccaride antigens.

28.  In this essentials coating microscopic gold
beads with the plasmid DNA and then
delivering the coated particles through the
skin into underlying muscle with an air
gun,called a gene gun.
 This allows very rapid delivery of vaccine to
large populations without the requirement
for huge supplies of needles and syringes.
 DNA vaccines are able to induce
protective immunity against a no. of
pathogens,including influenza and rabies
viruses.

31.  Use of DNA vaccines raises both humoral and
cellular immunity. The injected gene is
expressed in the injected muscle cell and in
nearby APCs. The peptides from the protein
encoded by the DNA are expressed on the
surface of both cell types after processing as
an endogenous antigen by the MHC class I
pathway. Cells that present the antigen in the
context of class I MHC molecules stimulate
development of cytotoxic T cells. The protein
encoded by the injected DNA is also expressed
as a soluble, secreted protein, which is taken
up, processed, and presented in the context of
class II MHC molecules. This pathway stimulates
B-cell immunity and generates antibodies and
B-cell memory .

32.  Most of the risk associated with
attenuated or killed whole organism
vaccines can be avoided with this.
 Vaccines that consists of specific,purified
macromolecules derived from
pathogens.
 3 general forms of vaccines that are
components or subunits of the target
pathogen in current use are inactivated
exotoxins or toxoids, capsular
polysaccharides and recombinant
protein antigens.

33.  Some bacterial pathogens, including those that cause diphtheria and tetanus,
produce exotoxins. These exotoxins produce many of the disease symptoms
that result from infection.
 Diphtheria and tetanus vaccines, for example, 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.
 Conditions for the production of toxoid vaccines must be closely controlled
to achieve detoxification without excessive modification of the epitope
structure.
 The problem of obtaining sufficient quantities of the purified toxins to
prepare the vaccines has been overcome by cloning the exotoxin genes and
then expressing them in easily grown host cells. In this way, large quantities
of the exotoxin can be produced, purified, and subsequently inactivated.
 Passive immunity to toxin can be induced by transfer of serum containing
anti-toxoid antibodies.eg:botulism is treated with horse antitoxin but to date
no toxoid vaccine against botulism has been developed for humans.

35.  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.
 Example: The current vaccine for Streptococcus pneumoniae,
which causes pneumococcal pneumonia, consists of 23
antigenically different capsular polysaccharides. The vaccine
induces formation of opsonizing antibodies and is now on the
list of vaccines recommended for all infants. The vaccine for
Neisseria meningitidis, a common cause of bacterial
meningitis, also consists of purified capsular polysaccharides.

37.  The gene encoding any immunogenic
protein can be cloned and expressed in
bacterial, yeast, or mammalian cells
using recombinant DNA technology. A
number of genes encoding surface
antigens from viral, bacterial, and
protozoan pathogens have been
successfully cloned into bacterial, yeast,
insect, or mammalian expression systems,
and the expressed antigens used for
vaccine development.

38.  The first such recombinant antigen vaccine
approved for human use is the hepatitis B
vaccine. This vaccine was developed by
cloning the gene for the major surface
antigen of hepatitis B virus (HBsAg) and
expressing it in yeast cells.
 The recombinant yeast cells are grown in
large fermenters, and HBsAg accumulates
in the cells. The yeast cells are harvested
and disrupted by high pressure, releasing
the recombinant HBsAg, which is then
purified by conventional biochemical
techniques. This recombinant hepatitis B
vaccine has been shown to induce the
production of protective antibodies. This
vaccine holds much promise for the 250
million carriers of chronic hepatitis B
worldwide.

39.  When the vaccines proposed consisting
of one or more proteins from the
pathogen.These proteins are
biosynthesized in large quantities using
appropriate cell lines and then purified
using procedures that donot introduce
contaminants into the product. The
problem arising is raising protective
immune responses against these
proteins. Certain adjuvants such
freund’s complete or incomplete
adjuvants,generate unacceptable side
effects. So ,strong adjuvant effective
compounds are searched without harm
to the vaccine

40.  SYNTHETIC PEPTIDES THAT MIMIC THOSE
EPITOPES AND USE THE PEPTIDES AS
VACCINES

44.  THEY GENERALLY REQUIRE STRONG
ADJUVANTS AND THESE ADJUVANTS
OFTEN INDUCE TISSUE REACTIONS.
 DURATION OF IMMUNITY IS GENERALLY
SHORTER THAN THE LIVE VACCINES.
 A PATHOGEN CAN ESCAPE IMMUNE
RESPONSES TO A SINGLET EPITOPE VERSUS
MULTIPLE EPITOPE VACCINES.

45.  Conjugate vaccines are somewhat similar to recombinant
vaccines: they’re made using a combination of two
different components. Conjugate vaccines, however, are
made using pieces from the coats of bacteria. These
coats are chemically linked to a carrier protein, and the
combination is used as a vaccine. Conjugate vaccines
are used to create a more powerful, combined immune
response: typically the “piece” of bacteria being
presented would not generate a strong immune response
on its own, while the carrier protein would. The piece of
bacteria can’t cause illness, but combined with a carrier
protein, it can generate immunity against future infection.
The vaccines currently in use for children against
pneumococcal bacterial infections are made using this
technique.

46.  a preparation of attenuated or killed
bacteria, used to immunize against
organisms injected, or sometimes for
pyrogenetic effects in treatment of
certain noninfectious diseases.

47.  The primary risk associated that vaccines
utilize the live organism is that the
vaccines itself causes illness.
 Another risk is that the vaccine may
behave as a super antigen and over
stimulate the immune system.
 Yet a third risk is that some individuals
may have an allergic reaction to the
vaccines.