types of vaccines and their clinical trails phase 1, phase 2, phase 3

1. Types of Vaccines and their Clinical Trials (Phase 1,2,3)
Introduction
Itis suspension of weakened, killed, or fragmented microorganisms or toxins
or of antibodies or lymphocytes that primarily used to preventdisease.
Vaccine can provideactive immunity against a harmfulagent by stimulating
the immune systemto fight against the infectious agents.
IMMUNIZATION
Itis the process by which a person is made immune or resistant to an
infectious disease, typically by administrating a vaccine. Vaccine stimulates the
body own immune systemto protect the person against subsequentinfection
or disease.
HISTORYOF VACCINES
The first vaccinewas introduced by Edward Jenner in 1796, used cowpoxvirus
to protection against smallpox virus, which is a related virus in humans.
In 1881 Louis Pasteur demonstrated immunization against anthraxby
injecting sheep with a preparation containing attenuated forms of the bacillus
that causes the disease. Four years later he developed a protective suspension
against rabies.
After Pasteur’s time, a widespread and intensive search for new vaccines was
conducted, and vaccines against both bacteria and viruses wereproduced, as
well as vaccines against venoms and other toxins. Through vaccination,
smallpox was eradicated worldwideby 1980, and polio cases declined by 99
percent.
TYPES OF VACCINES
1. Live-attenuated vaccines
Live vaccines use a weakened (or attenuated) form of the germ that causes a
disease.
Because these vaccines are so similar to the natural infection that they help
prevent, they create a strong and long-lasting immune response. Just1 or 2

2. doses of mostlive vaccines can give you a lifetime of protection against a germ
and the disease it causes.
LIMITATION
Because they contain a small amount of the weakened live virus, somepeople
should talk to their health careprovider before receiving them, such as people
with weakened immune systems, long-term health problems, or people who
had an organ transplant.
They need to be kept cool, so they don’t travel well. That means they cannot
be used in countries with limited access to refrigerators.
These used against the Smallpox, Chickenpox.
2. Inactivated vaccines
Inactivated vaccines use the killed version of the germ that causes a disease.
Inactivated vaccines usually don’t provideimmunity that is as strong as live
vaccines. So you may need several doses over time in order to get ongoing
immunity against diseases.
These used against the Hepatitis A, Polio, Rabies.
3. Toxoid Vaccines
Toxoid vaccines use a toxin made by the germ that causes a disease. They
create immunity to the parts of the germ that causea diseaseinstead of the
germ itself. That means the immune responseis targeted to the toxin instead
of the whole germ.
Like some other types of vaccines, you may need booster shots to get ongoing
protection against diseases.
These used against the Tetanus.
4. Subunit, recombinant, polysaccharide, and conjugatevaccines
Subunit, recombinant, polysaccharide, and conjugatevaccines usespecific
pieces of the germ like its protein, sugar, or capsid.
Because these vaccines use only specific pieces of the germ, they give a very
strong immune responsethat is targeted to key parts of the germ. They can
also be used on almost everyonewho needs them, including people with
weakened immune systems and long-term health problems

3. LIMITATION
These vaccines may need booster shots to get ongoing protection against
diseases.
These used against the Hepatitis B,
Futureof Vaccines
1. DNA Vaccines
2. Recombinant Vector Vaccines
These vaccines are experimental Vaccines Still in experiment stages and
severaltypes are being tested in humans like Influenza vaccines (DNA Vaccine)
and DPT(Recombinant vaccine).
CLINICAL TRAILS
The World Health Organization has made certain guideline and requirements
that has to be full filled in evaluation of vaccines that is good manufacturing
practice for pharmaceutical preparations, good manufacturing practice for
biological products, regulation and licensing of biological products in countries
with newly developing regulatory authorities and guidelines for national
authorities on quality assurancefor biological products.
REGULATIONOF VACCINES
Itis divided into three stages
1 Development Stage (it consists of two parts, preclinical research and
development, and clinical research and development.)
2. Licensure
3. Post licensure

4. Preclinical Research
Preclinical research and development are carried out in the laboratory using in-
vitro techniques or, when necessary, in-vivo techniques in animals. The data
frompreclinical and laboratory research includedetails of the development
and production of a vaccine together with reports of control testing, which
should be adequate to justify subsequentclinical studies in humans.
Phases of Clinical Trials
Clinical trials in humans are classified into three phases: phase1, phase 2 and
phase3.
This is in addition to ethical clearance which is required for clinical trials in all
countries. All studies of human subjects requireproper ethical review.
PHASE1
In Phase1 clinical studies carry out initial testing of a vaccine in small numbers
(e.g. 20) of healthy adults, to test the properties of a vaccine, its tolerability,
and, if appropriate, clinical laboratory and pharmacologicalparameters. Phase
1 studies are primarily concerned with safety.
PHASE2
In Phase2 studies involve larger numbers of subjects and are intended to
providepreliminary information about a vaccine’s ability to produceits desired
effect (usually immunogenicity) in the target population and its general safety.
To fully assess theprotective efficacy and safety of a vaccine,
PHASE3
In phase3 clinical trial is the pivotal study on which the decision on whether to
grant the licence is based and sufficient data haveto be obtained to
demonstratethat a new productis safeand effective for the purposeintended.
By the beginning of the phase3 stage of development, a vaccineshould have
been fully characterized and the final manufacturing process, specifications
and batch release testing procedures should havebeen established. An
application for marketauthorization may be submitted to a national regulatory
authority on the basis of the data from phase 3 testing and if approved, the
vaccine then becomes commercially available in that particular country.

5. If a productcontains or consists of genetically modified organisms an
environmental risk assessmentshould also be undertaken and approved by the
appropriateagency.
The structureof the clinical development programmemustbe tailored to the
type of vaccine and the antigenic content. For example, the clinical evaluation
of a vaccine that contains only novel antigen(s) may of necessity be very
different fromthat of a vaccinethat contains one or more previously evaluated
antigens. Such factors also influence whether clinical protection trials will be
required, whether or not they arefeasible, or whether an approvalmay
reasonably be based on immunogenicity data. In all instances, it is the
obligation of the applicant to justify the content and structureof the clinical
development programme. Pre-submission meetings with regulatory authorities
may assistin ensuring that the content of the final data package is likely to be
acceptable.
Reference
World Health Organization
Submitted by
Vivek Singh