Professional Documents
Culture Documents
Introduction:
Vaccines are a health technology designed to
prevent infections of various
kinds
by
promoting
an
immune response.
Interestingly,
the
word
vacca
meaning
cow,
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
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).
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
Vaccines
immune
system
has
memory
cells
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
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
Relation to AIDS
Vaccines
a particular way so it will concerns.
not be harmful
Examples: measles vaccine, produce similar results and are also safe
oral polio vaccine (Sabin),
vaccine.
Antibodies lock on to
Vaccines
the antigen/protein of
the pathogen
concepts.
Certain subunit
vaccines are made from
smaller pieces of
proteins called peptides
contains instructions or
a code to make
protein(s)
equipment to produce
some protein(s) of the
pathogen encoded by
Vaccines
the gene(s)
harmless or very
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
vaccinated
animals
from
infected
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
epitome
some
vaccines.
of
To
these
be
immune
made
to
response
broaden
to
the
different
epitomes.
13
Vaccines
protein
Immunosorbent
columns
with
monoclonal
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,
15
Vaccines
They are also called Human Herpes Virus 1 and 2
(HHV-1
and
HHV-2)
and
are
neurotropic
and
nervous
system,
accounting
for
their
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.
vastly reduces
reducing
milk
swine,
their
weight
output.
Cattle,
sheep,
goats,
and
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
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
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.
Therefore,
small
peptides
that
are
22
Vaccines
the
antigen
processing
pathway.
Consequently,
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]
epitopes
were
more
potent
immunogens
when
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
vaccines
generating
are
broad
typically
immunity
multivalent
against
in
several
26
Vaccines
overcome
by
the
coadministration
of
potent
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
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.
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
regarded
as
the
vaccines.
third
The
revolution
strategy
of
in
DNA
the
relevant
immunogenic
protein is isolated,
cloned
and
then
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
humoral
antibody
34
Vaccines
response
and
cell-mediated
response.
It
is
and
do
not
express
co-stimulatory
an
individual
immunogen-encoding
into
which
gene
is
the
concerned
introduced
and
35
Vaccines
simple infusion, implantation, encapsulation, etc.
This approach although more cumbersome, has the
advantage of enabling control of the modified cells
within
containment.
cells
by
panicle
gun.
Antigen
genes
heat-stable
and
offers
other
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
37
Vaccines
normally
requires
immunization
with
live
of
the
antigen,
which
generates
improved
method
for
administering
these
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
39
Vaccines
and
meningococcal
infections,
polysaccharide antigens.
use
protective
Another shortcoming is
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.
41
Vaccines
vector
vaccines
are
based
on
variant),
and
ADV5
(adenovirus
5).
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
easy
to
produce
vaccines.
Recombinant
43
Vaccines
vaccines, subunit vaccines, synthetic peptides as
vaccines,
disabled
mutants
as
vaccines,
oral
products
for
the
cure
of
diseases.
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
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.
genetics,
chemistry,
microbiology,
46
Vaccines
biochemistry
etc.
Spectacular
advances
are
depended
on
empirical
methods,
is
responsible
antigenicity.
Existing
47
Vaccines
Live but attenuated organisms or
Products
detoxified.
of
micro-organisms
There
are
which
certain
are
deficiencies
evolve
and
may
produce
new
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
include
cell-mediated
immunity,
the
49
Vaccines
importantly, for many infections the production of
circulating
(secretary)
antibody
at
the
site
of
infection.
Inactivated
vaccines
are
made
from
virulent
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
immunological
memory,
and
of
of
vaccine
at
birth,
or
shortly
children.
Also
heat-stable
vaccines
be
51
Vaccines
new and improved vaccines. Reducing the need of
multiple
doses
without
compromise
on
the
level
of
protection
in
population.
The
52
Vaccines
other reasons which can not be ensured. Also
immunosuppressed individuals may show serious
side-effects
(illness)
due
to
natural
spread
of
general
requirements
for
successful
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
peptide
vaccines
Here
instead
of
which
syhesized
and
induces
used
for
immune
eliciting
response
the
is
antibody
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
for
preparation
of
live
disabled
typhoid
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
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,
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
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
causes
meningitis-B.
They
have
recently
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.
by
the
(Expanded
Programme
of
1982.
This
Health
Policy
reflected
India's
communicable
diseases
like
tuberculosis,
which
aimed
at
providing
coverage
of
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.
production
of
oral
polio
vaccines
(OPV),
61
Vaccines
India has a new $4 million program to produce
within
three
years
vaccines
for
communicable
R&D
projects
for
the
development
of
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,
according
to
another
estimate.
63
Vaccines
initiatives
to
promote
domestic
production
of
genetically
engineered
drugs
produced
by
and
foreign
subsidiaries
in
the
the
production
by
public
institutes.
adequate
to
meet
India's
demand.
64
Vaccines
The estimated demand of oral polio vaccines is
mainly
satisfied
by
imports.
DPT
(diphtheria/
tetanus
and
BCG
(anti-tuberculosis)
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-
research
has
identified
the
following
organizations
(GPOs),
and
related
Corporation,
Chiron
Behring,
Chiron
Serum
Production
&
Medicine
Goldstar
Development,
Chemical
Merck
&
Ltd.,
Medeva
Company,
Inc.,
Group
North
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.,
&
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
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
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
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
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
73
Vaccines
18
(Diphtheria-tetanuspertusis) vaccine.
Oral Polio Vaccine.
Haffkine Biopharmaceuticals Corp. Ltd.,
Typhoid vaccine. Triple
Mumbai.
Vaccine
19
Smithkline Beecham
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:
74
Vaccines
www.google.com
www.sci-techno.com
www.answers.com
www.scienceblog.com
en.wikipedia.org
75