Vaccines

Introduction:
Vaccines are a health technology designed to
prevent infections of various
kinds

by

promoting

an

immune response.
Interestingly,

the

word

vaccine comes from the latin

word

vacca

meaning

cow,

Why this word? it relates

back to the history of vaccine. Cow pox vaccine was
first used to treat small pox.

Definition of a Vaccine
A vaccine is a substance that is introduced into the
body to prevent infection or to control disease due
to

certain

pathogen

(any

disease-causing

organism, such as a virus, bacteria or parasite); the

vaccine teaches the body how to defend itself
against a pathogen by creating an immune response.
Vaccines can be introduced in different ways, such
as injection into the muscle (intramuscular) or into

Vaccines
or under the skin (intradermal or subcutaneous); by
application to the skin (transdermal); by application
to the inside of the nose (nasal); or by being
swallowed (oral).

Why are vaccines important?

Vaccines are a significant a way of controlling the
spread of an infection in the body. By creating a
factor that can help the body to fight an infection.
Ultimately vaccines help to prolong life or to avoid
serious after-effects of an infection even if we get
through it.

How are vaccines created?

A vaccine is designed to protect the body against an
infection.
Typically vaccines work by enhancing the immune
system of the body. This is
done by using:
A dead version of the
infection

Vaccines
A harmless or much less severe version of the
infection.
Microscopic parts of the infective organisms
The body's defence then is able to create an immune
response and immune memory that can react
quickly if the full infection penetrates.

Vaccines

A is the full infective agent, it could a bacteria,

virus or a parasite.

A can be turned into B by a range of methods.

Or
C parts of the infective agent.
D is the vaccine being delivered. E, the body
produces antibodies and F remembers the type
of attack.

Vaccines

How Preventive Vaccines Work?

The following steps outline how a preventive
vaccine protects an individual from infection or
disease:
The vaccine introduces a small piece or a nonharmful form of the pathogen into the body. This
is called the foreign antigen (foreign indicates
that it is not from the persons own body).
The immune system in the body produces an
immune response to the pathogen by making
antibodies, killer cells or both.
The

immune

system

has

memory

cells

(producing antibodies) and memory T cells

(helping the production of antibodies or killer T
cells). The next time the real pathogen is
encountered; the immune system remembers it
and mounts a much larger and quicker response
than it would have if the person had never

Vaccines
received the vaccine. This is called immune
memory.
This larger and quicker immune response can
act in several ways to fight infection and/or
disease:
By stopping replication of the pathogen, so it
cannot infect more cells
By producing antibodies that attach to the
pathogen,

rendering

it

harmless

(antibody

response)
By producing immune cells that attack and kill
other cells that have been infected with the
pathogen (killer cell response).
Preventive vaccines are the traditional type of
vaccine, defined above. They are intended for people
who have not yet been infected. They prepare the
immune system to respond in case of future
exposure

to

the

pathogen.

Common

examples

include polio, measles, hepatitis B and tetanus

vaccines. All vaccines now marketed throughout the

Vaccines
world are preventive vaccines, although a few can
work if given immediately after exposure (such as a
rabies vaccine given right after a dog bite or a
tetanus booster vaccine given after a wound,
provided that the patient has been vaccinated before
and has immune memory). Most of the AIDS vaccine
candidates

now

being

tested

are

preventive

vaccines.
The table below lists some (but not all) types of
HIV vaccines, a general description of how each
works and, finally, how each concept relates to an
HIV vaccine in development.

Types of Vaccine
General
Vacci

Descriptio
n

Vaccines

Uses a weakened form Live attenuated vaccines are not

of the pathogen

Relation to AIDS

currently being developed for use in

Pathogen is changed in humans because of safety

Vaccines
a particular way so it will concerns.
not be harmful

Introduction of this form

of the pathogen into a
human will mimic true
infection (without
causing disease) and
will enable the body to
produce an immune
response

Scientists have studied live attenuated

vaccines against HIV in animals, where
they show high levels of protection.
These studies are helping scientists
understand the mechanism of
protection provided by live attenuated
HIV vaccines. Once they fully
understand the mechanism, they will
try to develop vaccine strategies that

Examples: measles vaccine, produce similar results and are also safe
oral polio vaccine (Sabin),

for use in humans.

intranasal live influenza vaccine

There are no current plans to test a live
attenuated HIV vaccine in human trials.

Most subunit vaccines

The first AIDS vaccines developed

contain a small protein and tested were designed using the

or piece of the

subunit concept. The first AIDS

pathogen; the protein

vaccine to go through complete

acts as the foreign

testing in humans, the AIDSVAX

antigen, which will start gp120 vaccine, was a subunit

the immune response

B cells of the immune

system will produce
antibodies against the
antigen

vaccine.

Antibodies lock on to

This vaccine failed to protect against

HIV infection in an efficacy trial,
which is one of the reasons scientists
are working to discover better vaccine

Vaccines
the antigen/protein of
the pathogen

concepts.

When the entire

pathogen enters the
body, the antibodies will
attach to the proteins on
the outer shell of the
pathogen, coating it and
making it harmless, or
neutralizing it

Certain subunit
vaccines are made from
smaller pieces of
proteins called peptides

Use copies of single or This is a common strategy being

multiple genes from the used for AIDS vaccine
pathogen; a gene is a

development, and many of the

small piece of DNA

current AIDS vaccine candidates

(genetic material) that

are DNA vaccines.

contains instructions or
a code to make
protein(s)

Genes enter into human

cells and use the cells

DNA vaccines will not cause HIV

infection, because the vaccines do not
contain all the genes of the live
pathogen.

equipment to produce
some protein(s) of the
pathogen encoded by

Vaccines
the gene(s)

When the protein is

produced, the immune
system sees it as a
foreign or harmful
antigen and produces
an immune response

The immune system

remembers this
response, which will
prepare a response
against the whole
pathogen

Use same strategy as

This is a common strategy being

DNA vaccines, but the

used for AIDS vaccine

genes are carried by a

development, and many of the

harmless or very

current AIDS vaccine candidates

weakened bacterium or are vector vaccines.

virus, called a vector

Genes are attached to

the DNA of the vector,
carrying the genes into
the human cell

Recombinant vector vaccines will not

cause HIV infection because it contains
copies of only one or several HIV
genes, not all of them. Many scientists
believe that the addition of a vector will

Once in the human cell, allow the vaccine to be more effective

genes produce

in creating an immune response than a

protein(s) to which the

DNA vaccine alone.

10

Vaccines
body produces an
immune response, as
described above for
DNA vaccines

Subunit Vaccines
Subunit vaccines are defined as those containing
one or more pure or semi-pure antigens. In order to
develop subunit vaccines, it is
critical to identify the individual
components out of a myriad of

11

Vaccines
proteins and glycoprotein of the pathogen that are
involved

in

inducing

protection.

proteins,

if

included

in

the

Indeed,

vaccine,

some

may

be

immunosuppressive, whereas in other cases immune

responses to some proteins may actually enhance
disease. Thus, it is critical to identify those proteins
that are important for inducing protection and
eliminate the others. Combining genomics with our
understanding of pathogenesis, it is possible to
identify specific proteins from most pathogens that
are critical in inducing the immune responses. The
potential advantages of using subunits as vaccines
are the increased safety, less antigenic competition,
since only a few components are included in the
vaccine, ability to target the vaccines to the site
where immunity is required, and the ability to
differentiate

vaccinated

animals

from

infected

animals (marker vaccines). One of the disadvantages

of subunit vaccines is that they generally require
strong adjuvant and these adjuvant often induce

12

Vaccines
tissue reactions. Secondly, duration of immunity is
generally shorter than with live vaccines. In addition
to using a whole protein as a vaccine, it is possible
to

identify

individual

epitomes

within

these

protective proteins and develop peptide vaccines.

The major disadvantage of peptide vaccines is that
they often need to be linked to carriers to enhance
their immunogenic and, secondly, a pathogen can
escape immune responses to a single epitome versus
multiple
overcome

epitome
some

vaccines.
of

To

these

disadvantages, chimeric peptides

can

be

immune

made

to

response

broaden
to

the

different

epitomes.

13

Vaccines

Steps in subunit vaccine

production
1. Identify protective proteins or epitopes on the
proteins. Once this is done, an individual can
either produce a subunit vaccine by rDNA
technology or y synthetic peptide technology.
2. Identify gene coding for the protein.
3. Clone the gene coding for the specific

protein

and express it in a suitable expression system.

4. Purify the protective protein to homogeneity
using bovine herpes virus-1. BHV-1 has four
glycoproteinGVPI, GVPII, GVPIII and GVPIV.
5.

Immunosorbent

columns

with

monoclonal

antibodies are prepared and used for purification

of large quantities of the BHV-I glycoproteins.
These glycoproteins are then mixed with the
adjuvant avidine and used to immunize animals
against BHV-I virus.

14

Vaccines
Herpes Vaccines
Herpes simplex virus:
Herpes simplex virus 1 and 2 (HSV-1 and HSV-2) are
two

species

of

the

herpes

virus

family,

Herpesviridae, which cause infections in humans.[1]

Eight members of herpesviridae infect humans to
cause a variety of illnesses including cold sores,
chickenpox or varicella, shingles or herpes zoster
(VZV), cytomegalovirus (CMV), and various cancers,
and can cause brain inflammation (encephalitis). All
viruses in the herpes family produce life-long
infections.

15

Vaccines
They are also called Human Herpes Virus 1 and 2
(HHV-1

and

HHV-2)

and

are

neurotropic

and

neuroinvasive viruses; they enter and hide in the

human

nervous

system,

accounting

for

their

durability in the human body. HSV-1 is commonly

associated with herpes outbreaks of the face known
as cold sores or fever blisters, whereas HSV-2 is
more often associated with genital herpes.

16

Vaccines
An infection by a herpes simplex virus is marked by
watery blisters in the skin or mucous membranes of
the mouth, lips or genitals.[1] Lesions heal with a
scab characteristic of herpetic disease. However, the
infection is persistent and symptoms may recur
periodically as outbreaks of sores near the site of
original infection. After the initial, or primary,
infection, HSV becomes latent in the cell bodies of
nerves in the area. Some infected people experience
sporadic episodes of viral reactivation, followed by
transportation of the virus via the nerve's axon to
the skin, where virus replication and shedding
occurs.[2]
Herpes is contagious if the carrier is producing and
shedding the virus. This is especially likely during an
outbreak but possible at other times. There is no
cure yet, but there are

17

Vaccines
treatments which reduce the likelihood of viral
shedding.

Herpes Simplex Virus

Foot and Mouth Vaccines

Foot and Mouth Disease:
Foot-and-Mouth Disease(FMD) is a severe, highly
contagious viral disease of cloven-hooved animals.
Although not usually fatal, it causes
suffering and

vastly reduces

animals commercial value

by
and

reducing
milk

swine,

their

weight

output.

Cattle,

sheep,

goats,

and

deer are highly susceptible

and can exhibit signs of clinical
illness after an incubation period of only 1 to 8 days;

18

Vaccines
however, the incubation period may last longer and,
especially in sheep and goats, signs of illness may go
undetected altogether. Clinical signs include fever
and blister-like lesions followed by erosions on the
tongue and lips; in the mouth, muzzle, and snout; on
the teats; between the hooves; and around the
digits.

Excessive

salivation,

lameness,

and

decreased feed consumption may also be observed.

FMD is widely believed to be the most economically
devastating livestock disease in the world. If it were
introduced into the United States, which is FMDfree, the disease could cause billions of dollars in
losses to the U.S. economy. Although the disease is
not a risk to humans, people who have worked
around or been near infected animals can carry and
spread the virus via their clothing, shoes, and
vehicles.

19

Vaccines

Foot-and-mouth disease
viruscoating protein
Virus classification
Group Group

IV

((+)ssRNA)
Famil Picornaviridae
y:
Genus Aphthovirus
:

Type species
Foot-and-mouth disease
virus

The FMD Vaccine

Vaccines are used to produce or stimulate immunity
against a particular disease. FMD vaccines are killed

20

Vaccines
virus preparations that are pure, safe, and effective,
and they are available to the U.S. Department of
Agriculture (USDA) through the North American
foot and- mouth Vaccine Bank. Mexico and Canada
are also members of the vaccine bank. There are
seven different types and more than 60 subtypes of
FMD virus, and there is no universal vaccine against
the disease. Vaccines for FMD must match to the
type and subtype present in the affected area. When
matched to type and subtype, the vaccine will
normally protect animals from developing clinical
signs of disease, but will not necessarily protect
animals against FMD infection. This is an important
point when considering whether to use FMD vaccine
or not.

21

Vaccines

Peptide Vaccines
Peptide vaccines follow the basic principle that T
lymphocytes recognize antigens only as peptide
fragments that are
generated
intracellularly and
bound
class

to
I

MHC
or

II

molecules on the
surface

of

the

antigen
presenting

cells.

Helper T cells recognize antigenic peptides that are

bound to the MHC class II molecules, whereas CD8
+ cytotoxic T cells are bound to the MHC class I
molecules.

Therefore,

small

peptides

that

are

present in the extracellular milieu can bind directly

to MHC class I or II molecules without undergoing

22

Vaccines
the

antigen

processing

pathway.

Consequently,

chemically synthesized peptides that are potent

immunogenic antigens are being pursued as vaccine
candidate for HCV (Table 4).
The rationale of this approach is based on the
knowledge that certain T-cell epitopes on the HCV
polyprotein may be important for viral clearance.
Using amino acid motifs to predict the binding of

peptides to MHC class I and II molecules, MHC-

23

Vaccines
peptide binding assays, and CTL and T helper
assays, several CTL and T helper epitopes on the
HCV polyprotein that may be important for the
design of a peptidevaccine have been identified.
Peptides containing epitopes from the core,[102-104]
NS4, 104 and NS5 102 regions have been shown to
induce strong CTL responses in BALB/c and HLAA2.1 transgenic mice. The covalent attachment of
the CTL peptide to a T helper peptide seems to be
crucial for generating a strong CTL response.[102-104]
In addition, enhancement of the immunogenicity of a
core-specific CTL epitope has been achieved by
substitution of one amino acid on the native peptide.
[105]

Furthermore, covalently linked T helper and CTL

epitopes

were

more

potent

immunogens

when

delivered as lipidated peptides.[104]

Other strategies for developing peptide vaccines are
using peptides to generate antibodies against linear
epitopes. Because HVR1 contains a neutralizing
epitope, it is an attractive target for peptide-based

24

Vaccines
vaccine. A chimpanzee that was immunized with
recombinant E1 and E2 glycoproteins together with
HVR1 peptides derived from a different isolate was
protected against inoculation of the isolate from
which the peptide sequence was derived.[106] In
addition, antiserum from this protected chimpanzee
was shown to neutralize the homologous strain by
inoculation of this mixture into another chimpanzee.
Similarly, rabbits that were immunized with a series
of synthetic HVR1 peptides 107 produced high titers
of broadly cross-reactive antibodies to HCV that
could block the binding of antibody-captured HCV to
MOLT-4 cells.
The most difficult problem of choosing the HVR1 as
the target for a HCV vaccine is the existence of
quasi-species in this region of HCV genome. The
screening of phage displayed peptide libraries has
been used to identify a consensus profile from over
200 HVR1 sequences of different viral isolates.
HVR1 sequences most commonly recognized by

25

Vaccines
patient sera and able to bind anti-bodies that crossreact with a large panel of HVR1 were identified
(Table 5).[108] A sequence pattern within these socalled mimotopes that was responsible for the
detected cross-reactivity could be developed. Mice
immunized with a mixture of the mimotopes shown
in Table 5 could generate antibodies that recognized
95% of the same panel of natural HVR1 variants.
This finding was confirmed by another study that
among the 25 different HVR1 proteins derived from
genotypes

1b,

the

sequence

similar

sequence

was

protein
to

the

the

most

that

contains

the

reported

consensus

frequently

recognized

protein by patient's sera.[109]

The major obstacles for a peptide-based approach lie
in the observation that single peptide without helper
function may be a poor immunogen, and many
effective

vaccines

generating

are

broad

typically

immunity

multivalent
against

in

several

different antigens. However, this limitation can be

26

Vaccines
overcome

by

the

coadministration

of

potent

adjuvants or the use of multiple epitopes vaccine

that contains a mixture of peptides.

Genetic Immunization
This is a variation of the recombinant vaccine
strategy. A cloned gene encoding an antigen is
delivered to cells in the ears of mice by biolistic
transformation system. The gene gets incorporated
into the chromosomal DNA and directs the synthesis
of the protein antigen. This in turn activates the
immune system of mouse to produce corresponding
antibodies against target antigen. This procedure
may be interesting because it surpasses costly and
time-consuming procedures of purifying an antigen
or creating recombinant vaccine. This approach is
referred to as "genetic immunization" and may be
useful for vaccination of domestic animals.
Genetic immunization is an attractive alternative for
antibody

production.

It

delivers

antigen-coding

27

Vaccines
plasmid DNA into the animal. The animal's cells
produce the protein from the expression vectors,
which stimulates the animal's immune system to
produce antibodies against that particular protein.
Genetic immunization offers enormous advantages
over the traditional protein-based immunization
method. DNA can be produced more quickly, cheaply
and

flexibly

than

protein.

Furthermore,

the

antibodies generated by genetic immunization are

usually of superior quality with regard to specificity,
affinity and recognizing the native protein.
The most important advantages of antibody
production by genetic immunization are as
follows:
It is faster because there is no need for purified
protein or peptide, just a DNA sequence file
It saves time and money
It generates antibodies with high affinity and
specificity

28

Vaccines
It generates antibodies against: native protein
structures, rarely expressed polypeptides, toxic

or self-antigens

Attenuated Vaccine
What is attenuated vaccine
A virulent organism that has been modified to
produce a less virulent form, but nevertheless

29

Vaccines
retains the ability to elicit antibodies against the
virulent form.

Advantages of attenuated vaccines:

1. The main advantage of attenuated vaccines
results primarily from their ability to replicate in the
host.

30

Vaccines
2. Since their mode of action is similar to natural
infections, immunity is generally of a broader
spectrum than it is with killed virus vaccines. Thus
they can induce a range of immune response both
locally as well as s systemically.
3. Attenuated vaccines develop immunity for longer
duration than killed virus vaccines.
4. Since the virus replicates in the host and
produces large quantities of proteins to which the
host responds, the possibility of injecting foreign
proteins is dramatically reduced with attenuated
virus vaccines.
Disadvantages of attenuated vaccines
1.Since the vaccines are produced by passage in
culture, to induce random mutation(s) or mutated
with a specific agent and thereby reduce virulence,
it is possible that passage in the natural host may
result in reversion back to virulence, e.g. attenuated
polio virus. In the case of polio, reversion can occur
within a few days of oral immunization.

31

Vaccines
2. Interference is also a potential problem. When
viruses are grown in culture, there is a possibility to
have other contaminating viruses present in it. For
example, the presence of BVD (a ubiquitous virus) in
viral vaccines grown for immunizing cattle is very
common. This virus is present in many of the cell
lines and foetal b vine sera than are used for
growing bovine viruses.
3. Live attenuated virus vaccine induces latent
infections and abortions if not administered properly
or if administered at the wrong time in the animal's
life.
4. These limitations have prompted the successful
development of vaccines, which are rather costly, at
least for
the

present.

32

Vaccines

DNA Vaccines
Recently,
developed,

vaccines
and

the

based

on

results

DNA

are

obtained

being

with

the

influenza

virus are quite exciting; these are

regarded

as

the

vaccines.

third
The

revolution

strategy

of

in
DNA

vaccines is as follows: the gene

encoding

the

relevant

immunogenic
protein is isolated,
cloned

and

then

integrated into a suitable expression vector.

This preparation is introduced into the individual to
be immunized. The gene is ultimately expressed in
the vaccinated individual and the immunogenic

33

Vaccines
protein is expressed in sufficient quantities to invoke
both humoral and cell-mediated immunities. It may
be pointed out cell-mediated immune response is
essential for recovery from infectious diseases. The
various approaches for DNA vaccines are as follows:
1. Injection of pure DNA (or RNA) preparation
into muscle.
2. Use

of

vectors

adenoviruses,

(e.g.

retroviruses,

vaccinia
oli,

viruses,

Salmonella

typhimurium, herpesviruses, etc.)

3. Reimplantation of autologous cells (cells of the
individual to be vaccinated) into which the gene
has been transferred, and
4. Particle gun delivery of plasmid DNA that
contains the gene in an expression cassette.
Injection of pure DNN/RNA into the skeletal
muscle leads to the uptake and expression of the
DNA in the muscle
cells, leading to both
a

humoral

antibody

34

Vaccines
response

and

cell-mediated

response.

It

is

surprising to note that the injected DNA is taken up

and expressed by the muscle cells with much
greater efficiency than in tissue culture.
The DNA appears either to integrate into the
chromosomal DNA or to be maintained for long
periods in an episomal form. The viral antigen is
expressed not only by the muscle cells but also by
dendritic cells in the area that take up the plasmid
DNA and express the viral antigen. The fact that
muscles express rather low-level of class I MHC
molecules

and

do

not

express

co-stimulatory

molecules suggests that dendritic cells in the area

may be crucial to the development of antigenic
responses to DNA vaccines.
Another approach is to remove cells from the body
of

an

individual

immunogen-encoding

into

which

gene

is

the

concerned

introduced

and

expressed. These cells are then reintroduced into

the body of the individual in a variety of ways, e.g.

35

Vaccines
simple infusion, implantation, encapsulation, etc.
This approach although more cumbersome, has the
advantage of enabling control of the modified cells
within

containment.

The immunogen-encoding gene may be integrated

into an expression plasmid, which is purified, coated
on gold or tungsten panicles and introduced into
skin

cells

by

panicle

gun.

Antigen

genes

introduced into the skin of mice and guinea pigs

elicited humoral immune response; it is not known if
cellular immunity is also induced. Plasmid DNA is
non-infectious,

heat-stable

and

offers

other

advantages over viral/bacterial vectors. The skin

cells are usually shed off in a few days after the
inoculation, so that there is no long-term persistence
of the modified cells.

36

Vaccines
DNA vaccine offers advantages over many of the
existing vaccines. The encoded protein is expressed
in

the

host

in

its

natural

form-there

is

no

denaturation or modification. The immune response

will be directed to the antigen exactly as it is
expressed by the pathogen. DNA vaccines induce
both humoral and cell-mediated immunity. This
stimulation of both arms of the immune response

37

Vaccines
normally

requires

immunization

with

live

attenuated vaccine. DNA vaccines cause prolonged

expression

of

the

antigen,

which

generates

significant immunological memory.

The practical aspects of DNA vaccines are also very
promising. Refrigeration is not required for the
handling and storage of the plasmid DNA, a feature
that greatly reduces the cost complexity of delivery.
The same plasmid can be custom-tailored to make a
variety of proteins, so that the same manufacturing
techniques can be used for different DNA vaccines,
each encoding an antigen from a different pathogen.
An

improved

method

for

administering

these

vaccines is to coat microscopic gold beads with the

plasmid DNA and then deliver the coated particles
through the skin into the underlying muscle with an
air gun (called a gene gun). This will allow rapid
delivery of a vaccine to large populations without
the requirement for massive quantities of needles
and syringes.

38

Vaccines
Tests of DNA vaccines in animal models have shown
that the vaccines are able to induce protective
immunity against a number of pathogens, including
the influenza virus. At present, there are human
trials underway with several different DNA vaccines,
including those for malaria, AIDS, influenza, and
herpes virus. Future experimental trials of DNA
vaccines will mix genes for antigenic proteins with
those for cytokines or chemokines that direct the
immune response to the optimum pathway. For
example, the IL-12 gene may be included in a DNA
vaccine. The expression of IL-12 at the site of
immunization will stimulate TH1 type immunity
induced
Results

by
to

date

with

the
DNA

vaccine

vaccine.
are

very

promising, and they are likely to be used fro human

immunization within the next few years. Some
drawbacks may prelude their universal application;
for example, only protein antigens can be encoded
certain vaccines, such as those for pneumococcal

39

Vaccines
and

meningococcal

infections,

polysaccharide antigens.

use

protective

Another shortcoming is

the present inability to use DNA immunization with

vaccines, such as the oral vaccines or those given as
a nasal spray, that are applied to mucosal surfaces.
The first published report from India indicates
modest success in the development of DNA vaccines
against rabies and Japanese encephalitis virus (JEV)
in experimental animals. The efficacy of DNA
vaccine (G protein) against rabies is correlated to
levels of neutralizing antibodies, whereas in the case
of JEV envelope protein, cell-mediated immunity
appears to be the major mechanism of protection.
There is great hope that DNA vaccines can offer
protection against serious infectious diseases. Most
likely it is to become a tool to benefit mankind in the
21st century as such or in combination with
recombinant/cell culture vaccines or as an adjunct
to chemotherapy (Padmanaban, 1999).

40

Vaccines
In the case of malaria, DNA vaccines have distinct
advantage, where plasmid DNA encoding different
antigens
procedure

and
can

prepared
be

by

mixed

the

and

same

genetic

administered.

mixture of 4 plasmid DNA (pfCSP, pfSSP2, pfEXP-l

and pfLSA-l) has been injected into Rhesus monkeys
and found to elicit multiple antigen-specific cytotoxic
T lymphocytes.
It has been reported that the DNA vaccine coding
for a mycobacterial heat-shock protein of molecular
weight 65000 (HSP65) when administered in 4
doses to mice, 8 weeks after intravenous injection of
virulent M tuberculosis H37RV, leads to a dramatic
decrease in number of live bacteria in spleen and
lungs, 2 months and 5 months after the first dose of
DNA. Certain other mycobacterial antigens and BCG
did not have this effect.

41

Vaccines

Recombinant Vector Vaccines

Recombinant

vector

vaccines

are

based

on

microorganisms such as viruses or bacteria that do

not cause disease in humans or have been weakened
so as not to cause disease. The viruses or bacteria
are used as vectors, or carriers, to deliver harmless
HIV genes into the cells of the body. The body
produces proteins from the HIV genes and these
proteins stimulate an anti- HIV immune response.
Some of the viral vectors being studied for HIV
vaccines include ALVAC (a canary pox virus), MVA (a
cowpox

variant),

and

ADV5

(adenovirus

5).

modified version of the bacterium Salmonella typhi

is also being studied as a vector for HIV vaccines.
Most of the recombinant vector vaccines for HIV
deliver several HIV genes.

42

Vaccines

CONCLUSION
Biotechnology for Vaccine Production
Appeared in Saket Industrial Digest (1st Nov. 1999)
Introduction:
Vaccination practice has a long history and perhaps
is the next reliable way of keeping good health after
diet and hygiene. Vaccines of earlier years were
mainly based on use of live (attenuated) or killed
pathogens
vaccines

or
had

their

detoxified

many

products.

limitations

and

These
certain

drawbacks. With the advent of biotechnology it has

become possible to develop cheaper, efficient, safer
and

easy

to

produce

vaccines.

Recombinant

43

Vaccines
vaccines, subunit vaccines, synthetic peptides as
vaccines,

disabled

mutants

as

vaccines,

oral

application of antigens, genetic immunization are

the few examples of new approaches with certain
advantages in their use.
Priorities in Vaccine Production:
While the WHO expects that there should be work
on for the eradication of diseases, most of the
biotechnology companies today are working on
medical

products

for

the

cure

of

diseases.

The WHO recently listed bacterial and amoebic

dysentery, cholera, typhoid as the diseases of top
priority for public health efforts. These diseases
alone are responsible for 80% of illness world-wide
and cause more than 20 million deaths annually.
Second in the priority are the parasite diseases such
as malaria, leishmaniasis, trypanosomiasis, oulliver
blindness. Together these diseases affect 1 billion
people. A group of rare disorders such as rashes,

44

Vaccines
leprosy, dengue fever and Japanese encephalitis are
also considered as high priorities.
Vaccines for various infectious diseases, cancer,
autoimmune diseases are being developed with the
efforts

in

biotechnology.

With

the

help

of

biotechnology, researchers are developing vaccines

for diseases from malaria to AIDS. At the same time,
they are working on an 'ideal children's vaccine'
which would deliver immunity against all serious
childhood diseases.
The whole cell cholera and typhoid vaccines which
were produced and used in India, performed so
poorly that mass immunization with these vaccines
was discontinued. Department of Biotechnology
(DBT) has also identified the pertussis component of
the DTP vaccine as of low efficacy and highly
reactogenic. The BCG vaccine that is currently used
world-wide is of doubtful efficacy. There is an need
of urgent efforts to improve this vaccine. An
improved pertussis component, like an acellular

45

Vaccines
(sub-unit) vaccine which is in an advanced stage of
clinical trials, would reduce the number of doses
(currently 3) required for DTP.
The combined vaccines with multiple antigens have
a future and DTP and MMR are already in use. If
there is incompatibility in antigens, a dual-barreled
syringe

is

used

for

compartment

delivery.

At present, vaccines are given at different ages for

the best immune response. Strains have to be
searched to give them after birth simultaneously
(today measles vaccine is given at 12-15 months,
while DTP at 3-4 months'age).
Multiple vaccines will be possible with genetic
engineering by adding relevent antigen genes from
different pathogens to a single 'Christmas tree
microorganism'. The above mentioned areas just
indicate the line of research and efforts towards
better vaccine production. Vaccine design is a
multidisciplinary effort and involves the work in
immunology,

genetics,

chemistry,

microbiology,

46

Vaccines
biochemistry

etc.

Spectacular

advances

are

expected in future in the field of vaccines.

Disadvantages with existing vaccines:

Vaccine manufacturing has been developed from the
early works of Pasteur and Koch. Most traditional
approaches

depended

on

empirical

methods,

principle for which were unknown. For both the

processes of attenuation and inactivation the early
researchers had no knowledge of the molecular
structures involved. Until recently there was no
clear idea of role of mutations in selection of
avirulent strains. Also there was no knowledge of
what selective damage occurs or what genetic
material

is

responsible

antigenicity.

Existing

vaccines were apparently successful and there were

not many highlighting reports on their drawbacks.
So far, vaccines were made using either
Killed organisms

47

Vaccines
Live but attenuated organisms or
Products
detoxified.

of

micro-organisms

There

are

which

certain

are

deficiencies

related to different vaccines manufactured until

now or difficulties are experienced in making
them.
These can be listed as : Incomplete inactivation of organism (say, in the
FMD viral vaccine preparation) can itself be the
source of infection. Also organisms may revert
to their patogenic forms.
Growing organisms (particularly viruses) in
animals or sometimes only in human cells is
difficult (human cell culture is also expensive to
maintain and is very slow-growing as compared
to bacterial cells).
Pathogens

evolve

and

may

produce

new

antigens and then earlier vaccines may prove

ineffective. Even a large number of serotypes
may be the cause for such problem.

48

Vaccines
It is difficult to grow some organisms to produce
vaccines, e.g. syphilis and leprosy causing
organisms.
Risk is involved in growing pathogens on large
scale for vaccine production.
Refrigerator
storage

temperatures

and

transport

are
of

required

for

live-attenuated

vaccines.
Disadvantage with killed vaccines are like :
more than one injection is required, presence
other cellular material may cause side-effects
and limited shelf life.
While making such a list, a point to be noted is
that vaccination with living organisms has the
advantage

that

employed

in

if

administered

natural

infection,

by
the

the

route

immunity

stimulated will include all the characteristics of

immune response induced by that infection itself.
These

include

cell-mediated

immunity,

the

production of circulating antibody and perhaps more

49

Vaccines
importantly, for many infections the production of
circulating

(secretary)

antibody

at

the

site

of

infection.
Inactivated

vaccines

are

made

from

virulent

pathogens by destroying their infectivity while

retaining their immunogenicity. These vaccines show
good antibody production but poor cell mediated
immunity. Inactivated bacterial toxins (of tetanus
and diphtheria organisms) can be considered to be
adaptation of this approach. Protective antibodies
react only with toxin and not with the infectious
bacterium.

Such

polysaccharides

vaccines
of

N.meningitidis

can

representatives

of

and

capsular

H.influenzae
be

today's

considered
concept

of

and
earlier
subunit

vaccines.
Newer Approaches of Immunization and Newer
Vaccines :

50

Vaccines
Understanding
pathogenesis

of
and

the

basic

protection

mechanisms
is

required

of
for

development of new vaccines. Knowledge of not only

virulence genes of pathogens but also of antigen
presentation,

immunological

memory,

and

of

antigens and epitopes recognised by the immune

system is required. The current efforts in vaccine
development are mainly to improve efficacy, safety
and stability of existing vaccines and to simplify the
vaccination schedule. Other attributes in mind are
administration

of

vaccine

at

birth,

or

shortly

thereafter so as to protect most vulnerable agegroup

children.

Also

heat-stable

vaccines

be

produced if possible so that requirement of cold

storage in transport can be avoided. The Children's
Vaccine Initiative (CVI), co-sponsored by the World
Health Organization, United Nations Development
Programme, United Nations Children's Fund and the
Rockefeller Foundation, is an international effort to
harness the tools of modern science to search for

51

Vaccines
new and improved vaccines. Reducing the need of
multiple

doses

without

compromise

on

the

protection is also one of the aim of new vaccines.

Vaccination by oral route may be useful particularly
in developing countries to avoid use of needles so as
to limit the risk of infection by agents such as HIV1.
Thus a perfect vaccine may be a fully defined, totally
synthetic, single dose and oral vaccine. While
thinking of an ideal live vaccine it would be a great
advantage if we have a vaccine that spreads
naturally but without causing a disease. This will
reduce problems in implementation of vaccination
programmes. Currently used live polio vaccine
spreads among contacts and helps to maintain
higher

level

of

protection

in

population.

The

objection to this concept can be from manufacturer's

view point as it would be uneconomic, as once
released there may not be a need again. From
ethical point of view there are group of individuals
who do not want to be vaccinated for religious or

52

Vaccines
other reasons which can not be ensured. Also
immunosuppressed individuals may show serious
side-effects

(illness)

due

to

natural

spread

of

vaccine. From safety point of view the possibility of

reversion of a strain to pathogenic form must be
eliminated. World-wide confidence in quality and
safety is important. Enhancement of both arms of
immune response is also a desired feature of ideal
vaccine.
Four

general

requirements

for

successful

vaccination are:(a) Activation of antigen-presenting cells (APCs)

(b) Overcoming genetic polymorphism in the host
and antigenic variation in the agent
(c) Generation of memory B and T cells
(d) Persistence of antigen
The contribution of biotechnological research so far

53

Vaccines
has been to produce the following types of vaccines
or to develop newer approaches of immunization :Vaccines using genetically engineered organisms This approach is particularly useful when it is
difficult

to

cultivate

the

organism

for

vaccine

production. Even if the pathogen can be cultivated,

gene cloning will be useful because antigen-specific
gene is engineered in non-pathogenic organism,
thereby reducing the risk during production. This
approach is effectively attempted for hepatitis, Foot
and Mouth Disease (FMD), syphilis, malaria, and
Aids.
Synthetic

peptide

vaccines

Here

instead

of

cultivating and using the pathogen, the antigen

(material)

which

syhesized

and

induces

used

for

immune
eliciting

response
the

is

antibody

production. If successful this approach will prove to

be highly specific, relatively in-expensive, safe and
effective alternative to conventional procedure. A
totally different approach to vaccine development

54

Vaccines
lies in chemical synthesis. Once scientists have
isolated the gene that encodes an antigen, they are
able to determine the precise sequence of amino
acids that make up the antigen. They then pinpoint
small key areas on the large protein molecule, and
assemble it chemical- by- chemical. Wholly synthetic
vaccines

are

being

explored

for

malaria

and

diarrheal diseases prevalent in developing countries.

Minicells as vaccines - Minicells do not replicate and
will not survive long in the body. So they may be
used to provide antigenic stimulus to the host by
inoculation via natural routes of infection without
the problems associated with administration of
infective organisms. This is yet in the trial state.
Disabling mutations resulting in suitable pathogens
(organisms) for vaccine - Pathogenic organisms may
be modified to reduce their virulence without
affecting their immunogenicity. Such efforts are
done

for

preparation

of

live

disabled

typhoid

organisms for oral vaccine and in case of cholera

55

Vaccines
vaccine. Thus vaccines will be effective because they
are administered by natural infection route but will
not cause damage by infection.
Anti-idiotypic vaccines - Antibodies to antibodies
have

the

immunological

properties

of

original

antigen. Such anti-idiotypic antibodies are surrogate

antigens and can be formulated as vaccine because
it mimics a specific antigen. This approach is tried
for vaccine for sleeping sickness and protozoal
parasite causing coccidiosis. This will enable the
vaccine production without requirement of regular
cultivation of pathogen for isolation of antigen or
use of the pathogen or the use of genetically
engineered organism carrying concerned gene.
Genetic immunization - Here instead of injecting the
antigenic material in form of live or killed pathogen
or as recombinant organism, the gene coding for
antigenic material is injected and incorporated in
host chromosome for stable maintenance. Thus
necessary antigen will be available by expression of

56

Vaccines
such gene which acts like a vaccine. There is yet a
lot of work required before this approach is brought
in practice. A DNA vaccine against AIDS is now
being tested in people.
Whatever

the

method

of

biotechnology

used,

vaccines produced by these techniques have definite

advantages over the current methods of vaccine
production.
These are:
More effective vaccines with increased response
and

high

specificity;

Long-lasting immunity;
No side effects, less toxicity;
Production methods easier and cheap; and
Novel vaccines.
A vaccine against Type I diabetes (insulin dependent
diabetes) is also in the development stage, as the
gene responsible for this form of diabetes has been

57

Vaccines
identified. Efforts are on to bring this vaccine in the
market in the near future.
The Market for Vaccines:
The fastest growing category of biotech products is
gene therapy while the second fastest growing
category of biotech products is vaccines with 44%
increase from 1995 to 1996. Vaccines are in
development for various types of cancers, AIDS,
rheumatoid arthritis and multiple sclerosis. Other
potential

uses

of

biotech

vaccines

include

contraception and treatment of psoriasis, influenza,

herpes

simplex,

Lyme

disease

and

infectious

diseases.
The market for vaccines is very immense. 200
million the world over suffer from Hepatitis B while
as many as 800 million doses of FMD (Foot and
Mouth disease of cattle) are required per year.
There

are

companies

four

leading
in

vaccine
the

manufacturing
world.

These are:

58

Vaccines
(1) Institut Merieux of France (Sales $ 300 million)
(2) Lederle (Cyanamid) of US.
(3) Merck of the US.
(4) Smithkline Beecham of Belgium.
Together these four companies account for half of $
1.3 billion a year world vaccine market. Today Cuba
is

one

of

the

world's

largest

producer

of

recombinant vaccine against hepatitis B. It is the

only producer of a vaccine against the bacterium
that

causes

meningitis-B.

They

have

recently

developed a promising recombinant vaccine which

protects cattle disease bearing ticks.
India's Vaccine Production and Demand
The lack of an effective health care system in India
is especially acute due to the high incidence of
communicable diseases. Between 1988-93, under 5
year mortality rate in India was 122 per 1000 live

59

Vaccines
births, or an estimated 3 million Indian children die
under the age of five each year, while an equal
number

become

disabled

due

to

diseases.

Preventive health care, of which the importance was

emphasized

by

the

(Expanded

Programme

of

Immunization) EPI, became the focal point of the

National Health Policy adopted by the Government
in

1982.

This

Health

Policy

reflected

India's

commitment to the international goal agreed upon in

Alma Alta: 'Health for All by the year 2000.' The
Policy enlarged the scope of preventive health care
by re-emphasizing the need to control additional
major

communicable

diseases

like

tuberculosis,

leprosy, diarrhoeal diseases, malaria and filaria.

Central to the Policy was the objective of providing
protection, illustrated by the expansion of the EPI
into the Universal Immunization Programme (UIP) in
1985,

which

aimed

at

providing

coverage

of

immunization to pregnant mothers and infants. The

UIP was adopted as a 'Technology Mission'. It was

60

Vaccines
designed as an end-to-end programme, i.e. to
promote, set up, undertake and monitor highly
competitive R&D activities in vaccinology, and to
achieve self-sufficiency in vaccine production. Under
the Technology Mission, the DBT was entrusted
with: (1) the production of vaccines hitherto not
produced in the country; and (2) R&D for new and
improved

vaccines.

DBT has set up three expert/technical committees in

1988 to evaluate the state-of-the-art technologies for
the

production

of

oral

polio

vaccines

(OPV),

inactivated polio vaccine (IPV) and vaccines against

measles and rabies. For the production of IPV and
rabies vaccine, the committees opted for the Vero
cell (micro-carrier) fermentation technology; for
production of the measles vaccine they chose the
chick embryo fibroblast cell culture technology; and
for OPV the committees selected primary monkey
kidney cell culture based technology.

61

Vaccines
India has a new $4 million program to produce
within

three

years

vaccines

for

communicable

diseases including malaria, tuberculosis, cholera,

Japanese encephalitis, rabies, and AIDS. The Indian
government has designated funds for vaccines and
given the task to the Department of Biotechnology.
The ambitious plan involves 12 basic research
institutions and two biotechnology firms. Vaccines
against cholera and rabies are expected to be put
into use in 2002. India's HIV vaccine research,
which is being conducted at the All India Institute of
Medical Sciences in New Delhi, is limited; however,
officials felt it was necessary to include it in the
initiative because the research is focusing on a
vaccine for the subtype-C strain, which is prevalent
in India.
Department of Biotechnology (DBT) has initiated
several

R&D

projects

for

the

development

of

improved vaccines. These vaccines could replace

poorly performing conventional ones, or broaden

62

Vaccines
their target range of communicable diseases. The
emphasis is on the build-up of a domestic capability
in vaccine production. Vaccination against polio,
tetanus and diphtheria, measles and hepatitis B as
the Expanded Programme of Immunization (EPI) is
India's committment to international goal of 'Health
for All by the year 2000.' DBT emphasizes the need
to control additional major communicable diseases
like

tuberculosis,

leprosy,

diarrhoeal

diseases,

malaria and filaria.

The Indian vaccine market is growing at a rate of 8
to 10 per cent per annum, but the country is still
spending US$ 12 million on imports of primary
vaccines. In 1993, the total turnover of Indian
production of human vaccines at manufacturers
level was around US$ 33 million. The vaccine
market in India is currently approximately $100
million growing at the rate of more than 20% per
year

according

to

another

estimate.

Recently the Government of India has taken some

63

Vaccines
initiatives

to

promote

domestic

production

of

vaccines. According to the New Drug Policy of 1994,

the

genetically

engineered

drugs

produced

by

recombinant DNA technology and specific cell/tissue

culture targeted drug formulations will not be under
price control for five years from the date of
manufacturing in India. Public sector has failed to
meet the expected advancements in production and
technology development. Therefore the lifting of the
price control aims at attracting private sector to
invest in these areas. Also importance of foreign
investment

and

foreign

subsidiaries

in

the

production of drugs using recombinant DNA is

recognised since their production in many vaccines
exceeds

the

production

by

public

institutes.

Therefore, there is a need to restrict the list of

vaccines reserved for the public sector to only a few
vaccines in which heavy public investment has been
made and for which the capacity in the public sector
is

adequate

to

meet

India's

demand.

64

Vaccines
The estimated demand of oral polio vaccines is
mainly

satisfied

by

imports.

DPT

(diphtheria/

pertussis/ tetanus booster), DT (diphteria/tetanus

booster),

tetanus

and

BCG

(anti-tuberculosis)

vaccines are supplied mainly by domestic producers.

For typhoid and hepatitis B, domestic production is
negligible and imports meet only a proportion of the
demand. India produces many traditional vaccines
but imports major ones such as Hepatitis A and B.
There is a need for new biotech-based vaccines for
HIV, cancer, diarrheal diseases, influenza virus,
contraception, rotavirus, TB, malaria, H. influenza
and pneumonia. Demand for Hepatitis B vaccine in
India per annum is 500 million doses.
Market Situation and Potential for Vaccines :
Worldwide revenues for pediatric vaccine markets
totalled more than 1.8 billion in 1998, with a growth
rate of 4.6 percent over the previous year, according
to Frost & Sullivan (www.frost.com). World Pediatric

65

Vaccines
Vaccine Markets is the latest strategic research from
Frost & Sullivan which analyzes the markets for the
full scope of pediatric vaccines, including those for
measles-mumps-rubella,

diphtheria-tetanus-

pertussis, polio, haemophilus influenzae B, hepatitis

B, and varicella.
Frost & Sullivan's World Pediatric Vaccine
Markets

research

has

identified

the

following

entities as market participants, distributors, group

purchasing

organizations

(GPOs),

and

related

organizations in the pediatric vaccine industry:

Abbott Laboratories, Biken Foundation, Bio Farma,
Chiron

Corporation,

Chiron

Behring,

Chiron

Vaccines, Cheil Jedang, CSL Limited, Eisai/Biken,

Human

Serum

Production

&

Medicine

Manufacturing Co., Korea Green Cross Corporation,

Lucky

Goldstar

Development,

Chemical

Merck

&

Ltd.,

Medeva

Company,

Inc.,

Group
North

American Vaccine, Inc., Pasteur Merieux Connaught,

Serum

Institute

of

India,

SmithKline

Beecham

66

Vaccines
Pharmaceuticals, Swiss Serum and Vaccine Institute,
Wyeth Lederle Vaccines and Pediatrics, American
Academy
Disease

of

Pediatrics,

Control

&

AmeriNet,

Prevention,

Center
COHR,

For
Inc.,

Department of Health and Human Services, General

Injectables
Network

&

Vaccines,

Alliance,

Inc.,

McKesson

GeriMed,
HBOC,

Health
National

Institute of Allergy.
In India, similarly human diploid cell culture based
rabies vaccine and improved cell culture vaccines
against measles, mumps and rubella (MMR), and
influenza are being imported and consumed.
Several viral vaccines for poultry like La Sota,
infectious bronchitis, fowl pox, New Castle disease,
Ranikhet disease, Marek's disease, etc are being
produced in large quantities. The total production of
animal and poultry vaccines amounts to in excess of
Rs 500 million and this is expected to grow at the
rate of about 10 per cent per annum in quantitative
terms during the next five to eight years.

67

Vaccines
The human vaccine market, to a large extent, is
controlled by the private sector, with very few public
sector companies like the Haffkine Institute, Indian
Immunologicals, etc.
Genetically engineered as well as human plasma
derived hepatitis B vaccines are being developed
and marketed in the country by: recombinant DNA
derived vaccines : EngerixB ( Smith Kline), Enivac
HB (Panacea), Shanvac (Shanta Biotech) and plasma
derived : Hepavax (VHB Pharma).
A large chunk of the Indian vaccine requirement is
still

supplied

by

imports

or

by

multinational

pharmaceutical giants based in India. The current

imports of these vaccines vary between 50,000 and
400,000 doses per annum, and are considered low
primarily due to their higher unit costs.
Several other vaccines like attenuated oral as well
as Vi antigen based injectable typhoid vaccine, H
influenza type B, meningitis and varicella (chicken
pox) vaccines are also required in the country in

68

Vaccines
sizable

quantities

although

these

are

not

yet

available.
During the year 1993, the turnover of human
vaccines in the country at manufacturer's level was
estimated to be of the order of Rs 1035 million for
active vaccines and about Rs 230 million in terms of
sensitized equine anti-sera.
The total turnover of sera and vaccines used for
human ailments is Rs 1265 million. The vaccine
market is growing at the rate of 8-10 per cent
annually in quantitative terms with the equine antisera market being almost static.
There are opportunities for the setting up of basic
production facilities for MMR, measles, cell cultured
rabies vaccines, recombinant Hepatitis vaccine, oral
and injectable typhoid (Vi antigen based) and other
vaccines as the demand is increasing and the
current production base is not sufficient for most of
these vaccines. Besides, the sale of these products is

69

Vaccines
primarily through private consumption by physicians
who exhibit ability to pay higher prices.
The Indian Expanded Programme of Immunization
(EPI) has to cater to about 23 million new borns
against childhood diseases and an equal number of
pregnant women against tetanus, which calls for
making

available

in

very

large

quantities

of

vaccines.
However, abundant capacities have already been
created in the country for the production of vaccines
against

Tetanus,

Diphtheria,

Pertussis

(and

combinations thereof like DPT and DT), BCG and

measles. Sheep brain derived as well as chick
embryo cell culture based rabies vaccines, yellow
fever, Japanese encephalitis vaccines, inactivated
cholera

and

typhoid

vaccines

are

also

being

produced locally.
In addition to active vaccines sensitized equine antisera against tetanus, gas gangrene, rabies and
snake

venom

are

also

produced

locally.

70

Vaccines
manufacturing

unit

with

an

annual

production

capacity of 100 million doses of oral polio vaccine

was set up by the central government at Bulandshah
(UP) through technology consultancy with Russia
and the unit was commissioned in 1994.
Currently vaccines against FMD, anthrax, BQ, MCC,
and enterotoximia, rinderpest, rabies, and sheep pox
are being produced in the country in abundant
quantities. The poultry industry is also developing
fast in the country.
A manufacturing unit with an annual production
capacity of 100 million doses of oral polio vaccine
was set up by the central government at Bulandshah
(UP) through technology consultancy with Russia
and the unit was commissioned in 1994.

Table - 1 Requirement of Vaccines in

India (Million Doses)
Name of Vaccine
DPT
DT
Tetanus Toxoid

1994-95
105
50
180

1999-2000
114
57
200

71

Vaccines
BCG
Polio
Measles
MMR
Rabies (Sheep brain-based)
Rabies (Cell cultured)
Hepatitis B (Plasma derived)
Hepatitis B (Recombinant)
Typhoid (Attenuated oral and injectable)
H. influenzae Type B
Meningitis

41
105
42
5
1
3
0.1
1
10
1
0.5

43
134
46
7.5
1.5
5
0.2
4.5
50
5
2

Table - 2 Vaccine Manufacturers in

India
No.
1
2
3
4

Institute / Company

Vaccines produced
DPT, DT, tetanus, cholera
Central Research Institute, Kasauli,
and typhoid through
Himachal Pradesh
fermentor and other
conventional techniques
BCG Laboratory, Quindy, Madras
BCG vaccine
Applying biotechnology for
The National Institute of Immunology
vaccine development,
(NII), New Delhi
anti-fertility vaccine
The International Centre for Genetic Production of a
Engineering and Biotechnology (ICGEB), recombinant version of the
New Delhi
anti-fertility vaccine.
Development and import
Hoechst India (Hoechst Marion Roussel), of oral and injectable
Mumbai
vaccine against typhoid,
rabies vaccine

72

Vaccines

7
8
9

10

11
12
13
14
15
16
17

Development and import

of oral and injectable
vaccine against typhoid,
Cadila
genetically engineered
vaccine against hepatitis
B in an advanced stage of
laboratory development.
importing and marketing
Cadila group, Alidac
an anti-rabies vaccine
DTP (diphtheria/
Glaxo
pertussis/ tetanus)
production
DTP (diphtheria/
Biological Evans Ltd.
pertussis/
tetanus)production
DTP (diphtheria/
pertussis/ tetanus)
Serum Institute of India
production, AntiRabies
vaccine, Hepatitis B
vaccine
R&D work on hepatitis B
Panacea Biotech
and oral polio vaccine
R&D work on hepatitis B
Shantha Biotech
and oral polio vaccine
Wochardt Ltd.
Hepatitis B vaccine
Bharat Immunological and Biological Polio vaccine and
Corporation Ltd., Bulundshar, New Delhi. Importers of vaccine.
FMD vaccine, Rabies
Indian Immunologicals, Hyderabad.
vaccine and Poultry
vaccines.
Inactivated Polio vaccine,
Indian Vaccines Corporation Ltd.,
Rabies and Measles
Gurgaon
vaccine.
Bengal Immunity Ltd.
Triple Vaccine i.e. DTP

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18

(Diphtheria-tetanuspertusis) vaccine.
Oral Polio Vaccine.
Haffkine Biopharmaceuticals Corp. Ltd.,
Typhoid vaccine. Triple
Mumbai.
Vaccine

19

Smithkline Beecham

Hepatitis B vaccine.

20 million doses per

20 Torrant Scitech (I) Pvt. Ltd., Ahmedabad. annum of Hepatitis B
vaccine.

BIBLIOGRAPHY
Books:
International Marketing
Magazines:
Sci - Tech March3, 2007 subscription
DNA August 5, 2007 subscription
Articles:
The Times of India- August 31, 2007
DNA - April 7, 2007
Hindustan Times- January20, 2008
Websites:

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www.google.com
www.sci-techno.com
www.answers.com
www.scienceblog.com
en.wikipedia.org

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