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VACCINE
1. INTRODUCTION
i. HISTORY.
ii. CONCEPT OF VACCINE.
iii. HOW IT WORKS.
2. NEED AND NECCESITY OF VACCINE.
3. NEWER VACCINE.
i. RECENTALY DEVELOPED VACCINE
ii. DEVELOPING VACCINE
iii. FUTURE VACCINE
INTRODUCTION
• “A vaccine is a biological preparation that
improves immunity to a particular disease.”
• A vaccine typically contains an agent that
resembles a disease-causing microorganism, and
is often made from weakened or killed forms of
the microbe.
• The agent stimulates the body's immune system to
recognize the agent as foreign, destroy it, and
"remember" it, so that the immune system can
more easily recognize and destroy any of these
microorganisms if later encounters.
• Vaccines can be prophylactic (e.g. to prevent
or ameliorate the effects of a future infection
by any natural or "wild" pathogen), or
therapeutic (e.g. vaccines against cancer are
also being investigated).
history
 The Indian historian D.P. Agrawal suggests that the practice originated in
India.[3] A religious rite having this effect was attributed to the
physician Dhanvantari, founder of the Vedic tradition, in about 1500
BCE.[4].
 The earliest written record of inoculation is thought to be found in 8th
century India, when Madhav wrote the Nidāna, a 79-chapter book which
lists diseases along with their causes, symptoms, and
complications.[6] According to Donald R. Hopkins (2002), Madhav
included a special chapter on smallpox (masūrikā) and described the
method of inoculation to protect against smallpox.
In the 18th century Dr. J.Z. Holwell wrote the most detailed account
for the college of Physicians in London, describing not only
inoculation, but also showing that the Indians knew that microbes
caused Small Pox.
Prior to vaccination, inoculation was practised, and brought to the
West (EUROPE ) in 1721 by Lady Mary Wortley Montagu, from the
Turkey
First Story of Vaccine
• Sometime during the 1770s Edward Jenner heard
a milkmaid boast that she would never have the
often-fatal , disfiguring disease smallpox, because
she already had cowpox, which has a very mild
effect in humans. In 1796, Jenner took pus from
the hand of a milkmaid with
cowpox, inoculated an 8-year-old boy with it,
afterwards observing that the boy did not catch
smallpox. Further experimentation demonstrated
the efficacy of the procedure on an infant. Since
vaccination with cowpox was much safer than
smallpox inoculation. the latter, widely practiced in
England & it banned in 1840.
• Louis Pasteur generalized Jenner's idea by
developing what he called a rabies vaccine. Edward Jennar
MILE STONE of vaccine HISTORY
18th century
• 1879 First vaccine for cholera
• 1885 First vaccine for rabies by Louis Pasteur
• 1890 First vaccine for tetanus
• 1896 First vaccine for typhoid fever
• 1897 First vaccine for bubonic plague
1796 First Vaccine for Smallpox ( the first vaccine ever developed )
19th century
20th century
• 1921 First vaccine for diphtheria
• 1921 First vaccine for tuberculosis
• 1926 First vaccine for pertussis (whooping cough)
• 1932 First vaccine for yellow fever
• 1937 First vaccine for typhus
• 1945 First vaccine for influenza
• 1952 First vaccine for polio by Jonas Salk
• 1954 First vaccine for Japanese encephalitis
• 1954 First vaccine for anthrax
• 1957 First vaccine for adenovirus-4 and 7
• 1962 First oral polio vaccine
• 1963 First vaccine for measles
• 1967 First vaccine for mumps
• 1970 First vaccine for rubella
• 1974 First vaccine for chicken pox
• 1977 First vaccine for pneumonia (Streptococcus
pneumoniae)
• 1978 First vaccine for meningitis ( Neisseria meningitides )
• 1981 First vaccine for hepatitis B (first vaccine to target a
cause of cancer.)
• 1985 First vaccine for Haemophilus influenzae type b (HiB)
• 1992 First vaccine for hepatitis A
• 1998 First vaccine for Lyme disease
• 1998 First vaccine for rotavirus
• 2003 First nasal vaccine for influenza approved
in US (FluMist)
• 2006 1ST vaccine for Human Papillomavirus.
21st century
Term VACCINE AND TYPE
The term vaccine derives from Edward Jenner's 1796
use of cow pox (Latin variola vaccinia, adapted from the
Latin vaccīn, from vacca, cow), to inoculate humans,
providing them protection against smallpox.
• Types
Vaccines are dead or inactivated organisms or purified
products derived from them.
There are several types of vaccines in use.[7] These
represent different strategies used to try to reduce risk of
illness, while retaining the ability to induce a beneficial
immune response. So different type of vaccines are
Killed - Some vaccines contain killed, but previously virulent, micro-
organisms that have been destroyed with :- chemicals, heat, radioactivity
or antibiotics.
Attenuated—
•Some vaccines contain live attenuated microorganism. Many of these are
live viruses that have been cultivated under conditions that disable their
virulent properties, or which use closely related but less dangerous
organisms to produce a broad immune response. .
•They typically provoke more durable immunological responses and are
the preferred type for healthy adults. But they may get reverted to the
virulent form and cause the disease.[8]
Subunit :-
• Rather than introducing an inactivated or attenuated micro-
organism to an immune system (which would constitute a
"whole-agent" vaccine), a fragment of it can create an
immune response.
• Examples include the subunit vaccine against Hepatitis B
Virus that is composed of only the surface proteins of the
virus.
• Previously it extracted from the blood serum of chronically
infected patients, but now produced by recombination of the
viral genes into Yeast,
• Other examples are Human Papillomavirus (HPV) that is
composed of the viral major Capsid protein,
Toxoid--Toxoid vaccines are made from inactivated toxic
compounds that cause illness rather than the micro-
organism. Examples of toxoid-based vaccines
include tetanus and diphtheria. Toxoid vaccines are known
for their efficacy.
Conjugate – Certain bacteria have polysaccharide outer
coats that are poorly immunogenic. By linking these outer
coats to proteins (e.g. toxins), the immune system can be
led to recognize the polysaccharide as if it were a protein
antigen. This approach is used in the Haemophilus
influenzae type B vaccine
Carrier
protein
Polysaccharide linked to
carrier protein
Conjugate vaccine
Bacteria
Polysaccharide
(sugar) coating
Conjugation
Conjugation is the process of attaching (linking) the polysaccharide antigen to a
protein carrier (e.g. diphtheria or tetanus) that the infant’s immune system already
recognises in order to provoke an immune response
Recombinant DNA Vaccine
• In recombinant DNA Vaccine, immunogenic part of antigen produced
by recombinant DNA and that immunogenic part injected in body.
• Like in Hep-B vaccine , H.P.V. vaccine
Gene taken for Surface protein, of hep-b + yeast cell genome.
kept in culture media (work as a production unit)
Produce surface protein
purified surface protein use as vaccine
Valence ;- Vaccines may be monovalent (also
called univalent) or multivalent (also called polyvalent). A
monovalent vaccine is designed to immunize against a single
antigen or single microorganism.[11] A multivalent or polyvalent
vaccine is designed to immunize against two or more strains of
the same microorganism, or against two or more
microorganisms.[12] In certain cases a monovalent vaccine may
be preferable for rapidly developing a strong immune
response.[13]
Live attenuated – measles, mumps, rubella, oral
polio, BCG, yellow fever, varicella
Inactivated – influenza, rabies, anthrax, IPV,
pertussis
Inactivated toxins – tetanus, diphtheria
Subcellular fraction – pneumococcal, Hib, Men C
Genetically engineered – Hepatitis B
Examples of Vaccines
The efficacy of these vaccine.
• the disease itself (for some diseases vaccination
performs better than for other diseases)
• the strain of vaccine (some vaccinations are for different
strains of the disease)[4]
• whether one kept to the timetable for the vaccinations
(see Vaccination schedule)
• some individuals are "non-responders" to certain
vaccines, meaning that they do not generate antibodies
even after being vaccinated correctly
• other factors such as ethnicity, age, or genetic
predisposition.
HOW IT WORKS
Toxoids
Bacterial vaccines (in
general)
Viral vaccines (in general)
BCG
Vaccines administered orally
or intra-nasally
• Antitoxin neutralising antibodies
• Multiple antibodies
(neutralisation,opsonisation,
complement activation ...)
• Multiple antibodies
(neutralisation essentially)
which act before the viruses
penetrate the cell + cytotoxic T
cells
• Cellular mediated immunity
• Humoral immunity + mucosal
immunity (IgA)
NEED AND NECCESITY OF VACCINE
Always said “prevention is better then cure”
 Vaccines are the important tool in preventive medicine
as well as in public health.
 vaccines are the one of the important tool to control the
emergence of disease ,stop that to make public health
problem.e.g. swine flu pandemic
 Vaccines is work at very grass root level and compare
to treatment it become cost effective then other
measures e.g. Small Pox , Polio , Measles are good
examples
NEWER VACCINE
1. RECENTALY DEVELOPED VACCINE
2. DEVELOPING VACCINE
3. FUTURE OF VACCINES
SINGLE ANTIGEN VACCINE
1. Prevnar (pneumococcal conjugate vaccine) 2002
2. Flumist (1st live attenueted influenza vaccine ) 2003
3. 1st killed Influenza vaccine 2004
4. Menatra (new meningococcal vaccine ) 2005
5. Rotateq (Rota vaccine) 2006
6. HPV vaccine (Gardasil)2006
7. Varivax (for chicken pox)2007
8. Flumist nasal vaccine of 1st live attenueted influenza vaccine
9. Rotarix (rota virus vaccine) 2008
10. Influenza-A (H1N1) 2009
NAME
OF
VACCIN
E
APROVE
D BRAND
AGE
INDICATIONS & USAGE DOSAGE AND
ADMINISTRATION
Pneumoco
ccal
conjugate
vaccine
Prevnar 13 1. In children 6
weeks through 5
years of age
(prior to the 6th
birthday),
Active immunization for invasive
disease caused By streptococcus
pneumoniae serotypes 1, 3, 4, 5, 6A,
6B, 7F, 9V, 14, 18C, 19A, 19F and 23F.
Otitis media caused by Streptococcus
pneumoniae serotypes 4, 6b, 9v, 14,
18c, 19f, And 23f.
The four-dose immunization
series
Consists of a 0.5 ml
intramuscular injection
administered at 2, 4, 6, and 12-
15 months of age. (2.3)
2. In adults 50
years of age and
older
Active immunization for invasive
disease caused By streptococcus
pneumoniae serotypes 1, 3, 4, 5, 6A,
6B, 7F, 9V, 14, 18C, 19A, 19F and 23F.
Adults 50 years and older: a
single dose. (2.6)
C/I
1. Allergy to
contents
2. Premature baby 3.Immunocompromised
INDICATION AND USAGE :- age against Influenza disease caused by
Influenza Virus subtypes A and type B
DOSAGE & ADMINISTRATION :-
CONTRAINDICATIONS:- Hypersensitivity to eggs, egg proteins, gentamicin,
gelatin, or arginine, or life-threatening reactions to previous influenza
vaccination. (4.1)
• Concomitant aspirin therapy in children and adolescents. 900RS.
INDICATIONS AND USAGE :-Menactra vaccine is indicated for active
immunization to prevent invasi ve meningococcal disease caused by N
meningitidis serogroups A, C, Y and W-135. Menactra is approved for use
in individuals 9 months through 55 years of age. Menactra vaccine does not
prevent N meningitidis serogroup B disease. (1)
DOSAGE AND ADMINISTRATION A 0.5 mL dose for intramuscular injection.
• Children 9 through 23 months of age: Two doses, three months apart.
• Individuals 2 through 55 years of age: A single dose.
CONTRAINDICATIONS Severe allergic reaction (eg, anaphylaxis) after a
previous dose of a meningococcal capsular polysaccharide-, diphtheria
toxoid- or CRM197-containing vaccine, or to any component of Menactra
vaccine. (4)
• Rota shield:- in 1998, a rotavirus vaccine (rot shield, by Wyeth) was
licensed for use in the united states, but withdrawal from market due to
increased incidence of intussusception,in 1999-2000.
• Rotarix :-
• ROTARIX is indicated for the prevention of rotavirus gastroenteritis
caused by G1 and non-G1 types (G3, G4, and G9),
• ROTARIX is approved for use in infants 6 weeks to 24 weeks of age
dose 1 ml, gap between 2 dose should be 1 month
• CONTRAINDICATIONS :-
• congenital malformation of the
gastrointestinal tract,
• History of intussusception
• History of Severe Combined Immunodeficiency Disease (SCID).
• :- it is a live, oral pentavalent vaccine that
contains five rota viruses types.
• Dosage forms and strengths :- Rota-teq, 2 mL for oral use, is a
ready-to-use solution of live reassortant rotaviruses, containing G1,
G2, G3, G4 and P1A[8]
• Age - Administered as a 3-dose series to infants between the ages
of 6 to 32 weeks. The first dose of rotateq should be administered
between 6 and 12 weeks of age, with the subsequent doses
administered at 4- to 10-week intervals. The third dose should not
be given after 32 weeks of age.
• Contraindications - Hypersensitivity, History of Intussusceptions ,
Severe Combined Immunodeficiency Disease.
• 1250/-
ROTATEQ
INDICATIONS AND USAGE :-
girls and women 9 through 26 years of age for the prevention of the
following caused by HPV : - Cervical, vulvar, vaginal, and anal cancer &
Genital warts (condyloma acuminata)
boys and men 9 through 26 years of age for the prevention of the - Anal
cancer & Genital warts (condyloma acuminata).
DOSAGE AND ADMINISTRATION -- 0.5-mL suspension for intramuscular
injection at the following schedule: 0, 2 months, 6 months. (2.1)
DOSAGE FORMS AND STRENGTHS :- 0.5-mL suspension for injection as a
single-dose vial and prefilled syringe.
CONTRAINDICATIONS--Hypersensitivity, including severe allergic reactions to
yeast (a vaccine component), or after a previous dose of GARDASIL. 3100/-
• INDICATIONS AND USAGE :- VARIVAX is indicated for vaccination
against Varicella in individuals 12 months of age and older. The duration of
protection of VARIVAX is unknown; however, long-term efficacy studies
have demonstrated continued protection up to 10 years after vaccination.
• DOSAGE AND ADMINISTRATION: (FOR SUBCUTANEOUS ADMINISTRATION )
• Children :- 12 months to 12 years of age should receive a 0.5-mL dose
administered subcutaneously. If a second 0.5-mL dose is administered, it
should be given a minimum of 3 months later.
• Adolescents and Adults :-Adolescents and adults 13 years of age and
older should receive a 0.5-mL dose administered S.C. at elected date and
a second 0.5-mL dose 4 to 8 weeks later.
• CONTRAINDICATION :- Individuals with leukemia, lymphomas of any
type, or other malignant neoplasm affecting the bone marrow or lymphatic
systems. 1500/-
• Both vaccines are for influenza A H1N1 virus but basic difference is
panenza is non-adjuvant and humenza is adjuvant vaccine, so
humenza need less strenght of vaccine.
• STORAGE:-
• Store in a refrigerator between +2°C and +8°C.
• DISCARD opened vials within 7 days (opened vials can be used
for a maximum of 7 days) if kept between +2°C and +8°C.
DOSE AND SCHEDULE:
INSTRUCTIONS FOR VACCINE ADMINISTRATION:
• It is necessary to closely follow good practices of asepsis at each step of
handling.
• Before injection the vaccine should be allowed to reach room temperature
by gently swirling the vial between hands (not more than 5 minutes).
• Shake before each use.
• Each dose of vaccine must be withdrawn with a
new syringe and needle suitable for IMinjection
ROUTE OF ADMINISTRATION:
• The vaccine will be injected into a muscle.
1. Pediarix ( DTaP + IPV + HEP-B )2004
2. Proquad ( MMR + VARIVAX ) 2006
• Diphtheria and Tetanus Toxoid and Acellular Pertussis Adsorbed,
Hepatitis B (Recombinant) and Inactivated Poliovirus Vaccine
Combined].
• Recommended Schedule & DOSE : The primary immunization
series for PEDIARIX is 3 doses of 0.5 mL, given intramuscularly,
at 6- to 8-week intervals (preferably 8 weeks). The customary age
for the first dose is 2 months of age, but it may be given starting at
6 weeks of age.
• Contraindications:- Hypersensitivity to any component of the
vaccine, including yeast, neomycin, and polymyxin-B, is a
contraindication
• INDICATIONS AND USAGE :- ProQuad is a vaccine indicated for active
immunization for the prevention of measles, mumps, rubella, and varicella
in children 12 months through 12 years of age. (1)
• DOSAGE AND ADMINISTRATION :- A 0.5-mL dose for subcutaneous
injection only. The first dose is usually administered at 12 to 15 months of
age. A second dose, if needed, is usually administered at 4 to 6 years of
age.
• CONTRAINDICATIONS:- History of anaphylactic reaction to neomycin or
hypersensitivity to gelatin or any other component of the vaccine. Primary
or acquired immunodeficiency states. Family history of congenital or
hereditary immunodeficiency.
HIV VACCINE
In 1984, after the confirmation of the etiological
agent of AIDS by scientists at the U.S. National
Institutes of Health and the Pasteur Institute, the
United States Health and Human Services
Secretary Margaret Heckler declared that
a vaccine would be available within two
years. But still it is a dream.
The ineffectiveness of previously developed vaccines
primarily stems from two related factors.
• First, HIV is highly mutable. Because of the virus' ability to
rapidly respond to selective pressures imposed by the
immune system,
• Second, HIV isolates are themselves highly variable. HIV
can be categorized into multiple clades and subtypes with a
high degree of genetic divergence. Therefore, the immune
responses raised by any vaccine need to be broad enough
to account for this variability. Any vaccine that lacks this
breadth is unlikely to be effective.
Challenges in HIV Vaccine Research
• Viral Genetic Diversity: HIV is not just
one specific virus.
• Immune Protection: We don’t know
what immune responses are needed, or
how strong they need to be.
• Neutralizing Antibody: Difficult to
generate broadly neutralizing
antibodies.
• Vaccine Testing: Slow process, very
expensive
…but on the Brightside…
• Precedent from animal studies: Long-
term control of infection in vaccinated
monkeys
• Immune control of HIV-1: Infected
individuals control infection
• Vaccine Trials: In progress
Vaccine Vector Platform
• Vaccine Approach: Genetic engineer, doctors
characterize and optimize a viral vector system
that can be used to deliver HIV antigen(s) to
antigen presenting cells (APCs) and that could
also improve immune responses to induce long-
term immunological memory. Approach are--
• Viral Vectors
– HSV-based Amplicon Vector
– Recombinant Adenovirus Type 5 Vector
– Bacteriophage Lambda Vector
• A June 2005 study estimates that $682 million is spent on
AIDS vaccine research annually.[26]
• Economic issues with developing an AIDS vaccine include
the need for advance purchase commitment because after
an AIDS vaccine has been developed, governments and
NGOs may be able to bid the price down to marginal
cost.[27]
VaxGen USA
VaxGen Thai Trial
Step Trial
Thai Trial
Trial start/end
Trial analysis/results
First correlates
1990 1995 2000 2005 2010
1 year
1 year
6 months
16 months
HVTN 505 Enrollment in
process
Timeline of HIV Vaccine Efficacy Trials
From 1990 to 2010
VaxGen USA
VaxGen Thai Trial
Step Trial
Thai Trial
Trial start/end
Trial analysis/results
First correlates
1990 1995 2000 2005 2010
1 year
1 year
6 months
16 months
HVTN 505 Enrollment in
process
Recombinant gp120
No Efficacy
Timeline of HIV Vaccine Efficacy Trials
From 1990 to 2010
VaxGen USA
VaxGen Thai Trial
Step Trial
Thai Trial
Trial start/end
Trial analysis/results
First correlates
1990 1995 2000 2005 2010
1 year
1 year
6 months
16 months
HVTN 505 Enrollment in
process
Ad5 Gag Pol Nef
T cell vaccine
No Efficacy
Classification of all theoretically possible
HIV vaccines
• Any theoretically possible HIV vaccines must inhibit or stop the HIV virion
replication cycle.[28] So, the targets of the vaccine are the following phases of the
HIV virion cycle:
• Phase I. Free state
• Phase II. Attachment
• Phase III. Penetration
• Phase IV. Uncoating
• Phase V. Replication
• Phase VI. Assembling
• Phase VII. Releasing
• So, the possible approaches for the HIV vaccine are the following (in the bracket
specified the Phases were it is possible to do).
• Filtering virions from blood (Phase I
• Approaches to destroying or damaging the virion or its parts (Phase I-VII)
• By nature of method:
– Physical methods (Phase I-VII)
– Chemical and biological methods (Phase I-VII)
• By damaging target of the HIV virion structure:
– Damaging the Docking Glycoprotein gp120 (Phase I-III, VI, VII)
– Damaging the Transmembrane Glycoprotein gp41 (Phase I-III, VI, VII)
– Damaging the virion matrix (Phase I-III, VI, VII)
– Damaging the virion Capsid (Phase I-III, VI, VII)
– Damaging the Reverse Transcriptase (Phase I-VII)
– Damaging the RNA (Phase I-VII)
• Blocking the replication (Phase I).
• Inhibiting process of phases (drugs already
used for this approach).
• Inhibiting the functionality of infected cells
(Phase VI- VII).
• Approaches to catching the virion (Phase I-
III, VI, VII).
Future work
• First, greater translation between animal models and human
trials must be established.
• Second, new, more effective, and more easily produced
vectors must be identified.
• Finally, and most importantly, there must arise a robust
understanding of the immune response to potential vaccine
candidates.
• A vaccine, SAV001, that has had success in animal subjects
began Phase 1 human trials in London, Ontario in 2011.[30]
Transgenic plants
• Transgenic plants can be a convenient and efficient way
to obtain HIV vaccine. Plant-based vaccines, which are
easy to produce and administer, and require no cold chain
for their heat stability are, in principle, suited to such a
strategy. More recently, it has been shown that even
highly immunogenic, enveloped plant-based vaccines can
be produced at a competitive and more efficient rate than
conventional strategies
Malaria vaccine
Why a vaccine?
Data as of the end of 2008, WHO
61
Malaria vaccine community goal
• Strategic Goal: To develop an 80%
efficacious malaria vaccine by 2025 that
would provide protection for at least four
years
• Landmark goal: To develop and license a
first-generation malaria vaccine that has
protective efficacy of more than 50%
against severe disease and death and
lasts longer than one year
Malaria Vaccine Technology Roadmap
http://www.malariavaccineroadmap.net/
P. vivax and Pf / Pv transmission-blocking vaccines
Vaccines Under Development
• A completely effective vaccine is not yet available for
malaria, although several vaccines are under development.
SPf66 was tested extensively in endemic areas in the
1990s, but clinical trials showed it to be insufficiently
effective.
• Other vaccine candidates, targeting the blood-stage of the
parasite's life cycle, have also been insufficient on their
own.
• Several potential vaccines targeting the pre-erythrocytic
stage are being developed, with RTS,S/ ASO1 showing the
most promising results so far.
RTS,S/AS01 (commercial name: Mosquirix)
• which started Pivotal Phase III evaluation in May 2009.
• It is designed not for travellers but for children resident in
malaria-endemic areas who suffer the burden of disease
and death related to malaria.
• The RTS,S vaccine was engineered using genes from the
outer protein of Plasmodium falciparum malaria parasite
and a portion of a hepatitis B virus plus a
chemical adjuvant to boost the immune system response.
Result
• In October 2011 the group
reported first findings from
the Phase III trial of RTS,S
indicating that 46% of
15,460 inoculated infants
and children were protected
for 15 months.[5][6][7]
Vaccine development strategies for the future
• The development of a vaccine of therapeutic and protective
benefit against the malaria parasite requires a novel approach as
to date there are no vaccines available that effectively target a
parasitic infection.
• The focus so far has been predominately on the use of sub-unit
vaccines.
• The use of live, inactivated or attenuated whole parasites is not
feasible and therefore antigenic particles, or subunits, from the
parasite are isolated and tested for immunogenicity i.e. the ability
to elicit an immune response.
• The majority of subunits tested have been discussed above
and are frequently combined with adjuvants and specialised
delivery systems to increase the very variable level of immune
response.
• The most recent advances in the field of sub-unit vaccine
development include the use of DNA vaccination.
Vaccine for Dengue
• Despite decades of effort by many scientists to develop a vaccine for
dengue, no licensed vaccine is available. The problem begins with the virus
itself (or really, the viruses). Dengue is caused by infection with any of four
closely related dengue viruses, and a successful dengue vaccine must offer
immunity against all four.
• the Division of Vector-Borne Diseases (DVBD) at Fort Collins, CO, have
developed a dengue vaccine candidate that is now being clinically evaluated
in the United. States and Colombia for safety and efficacy
• The first human Phase-I trial showed that the vaccine was safe, well
tolerated, and produced antibody levels that should protect against all four
dengue viruses.
• Because of these encouraging results, a Phase-II clinical trial to assess
immunogenicity (ability to provoke an adequate immune response) will
begin in 2012.
• A successful Phase-II trial would be followed by Phase-IIb or
Phase-III trials to determine efficacy at a much larger scale.
Clearly, development and testing of a human vaccine requires
many steps.
• This technology has been awarded multiple U.S. and
international patents. CDC’s dengue vaccine team has
partnered with Inviragen, Inc., a Colorado-based vaccine
manufacturer.
• Inviragen is manufacturing the vaccine, named DENVax, and is
conducting clinical development and testing of the vaccine for
human use. The goal is to provide a safe, effective, and
affordable dengue vaccine
Leprosy vaccine
In brief
• A vaccine containing ICRC bacilli (which are cultivable
leprosy derived mycobacteria probably belonging to M.
avium intracellulare complex) was prepared in 1979 at
the Cancer Research Institute, Mumbai[12].
• Studies, both on humans and animals, show that the
ICRC bacilli exhibit antigenic cross-reactivity with
M.leprae with reference to both B and T cell antigens
(iii) FUTURE OF VACCINES
1. Therapeutic cancer vaccine
2. Biodefense and special
pathogen vaccines
1. Therapeutic cancer vaccine
.
A number of innovative vaccines are also in development
and in use:
1. Dendritic cell vaccines combine dendritic cells with
antigens in order to present the antigens to the body's
white blood cells, thus stimulating an immune reaction.
These vaccines have shown some positive preliminary
results for treating brain tumors.[9]
2. Vaccine for non infectious disease
•T-cell receptor peptide vaccines are under
development for several diseases using models
of Valley Fever, stomatitis, and atopic dermatitis.
These peptides have been shown to modulate
cytokine production and improve cell mediated
immunity.
3. Synthetic Vaccines
•Targeting of identified bacterial proteins that are involved
in complement inhibition would neutralize the key bacterial
virulence mechanism.[10]
•While most vaccines are created using inactivated or
attenuated compounds from micro-organisms, synthetic
vaccines are composed mainly or wholly of synthetic
peptides, carbohydrates or antigens that will produced
more strong immunity and can be expected to stay longer
or life time.
DNA VACCINES
INTRODUCTION
DNA vaccine is DNA sequence used as a vaccine.
This DNA Sequence code for antigenic protein of
pathogen.
As this DNA inserted into cells it is translated to form
antigenic protein. As this protein is foreign to cells ,
so immune response raised against this protein.
In this way ,DNA vaccine provide immunity against
that pathogen.
HISTORY
In 1990, University of Wisconsin, Jon Wolff found
that injection of DNA plasmids produce a protein
response in mice.
In 1993, Merck Research Laboratories, Dr. Margaret
Liu found that intramuscular injection of DNA from
influenzae virus into mice produced complete
immune response
In 1996, trials involving T-cell lymphoma, influenzae
& herpes simplex virus were started
DNA vaccines Vs Traditional vaccines
 Uses only the DNA from
infectious organisms.
 Avoid the risk of using
actual infectious
organism.
 Provide both Humoral &
Cell mediated immunity
 Refrigeration is not
required
 Uses weakened or killed
form of infectious
organism.
 Create possible risk of the
vaccine being fatal.
 Provide primarily
Humoral immunity
 Usually requires
Refrigeration.
DNA vaccines Traditional vaccines
HOW DNA VACCINE IS MADE
Viral gene
Expression
plasmid
Plasmid with foreign gene
Recombinant DNA
Technology
Bacterial cell
Transform into
bacterial cell
Plasmid
DNA
Plasmid DNA get
Amplified
Plasmid DNA Purified
Ready to use
METHODS OF DELIVERY
Syringe delivery:-
Either
intramuscularly
or
Intradermally
Contd..
Gene gun delivery:-
Adsorbed plasmid DNA
into gold particles
Ballastically accelerated
into body with gene gun.
ADVANTAGES
Elicit both Humoral & cell mediated
immunity
Focused on Antigen of interest
Long term immunity
Refrigeration is not required
Stable for storage
DISADVANTAGES
Limited to protein immunogen only
Extended immunostimulation leads to
chronic inflammation
Some antigen require processing which
sometime does not occur
CURRENT CLINICAL TRIALS
June 2006,DNA vaccine examined on
horse. Horse acquired immunity against
west nile viruses.
August 2007,DNA vaccination against
multiple Sclerosis was reported as being
effective.
SAFETY ISSUE WITH DNA
VACCINE
• Genetic Toxicity
• Integration of DNA vaccine into host Genome can cause
• Insertional mutagenesis
• Chromosome instability
• Turn ON Oncogenes
• Turn OFF Tumor suppressor genes
• Over Expression of DNA vaccine
• Generation of Autoimmune diseases
• Autoimmune Myositis
• Anti DNA Antibodies
• Autoimmune diseases
• Antibiotic Resistance
• Plasmid used is resistance to antibiotics for selection
CONCLUSION
DNA vaccines are in their early phase.
There are no DNA vaccines in market at
present. But this just the beginning .DNA
vaccines are going to be the vaccines of
next generation.
Conclusion
• Discovery of newer vaccine is a continuous process and it is
never going to stop.
• Newer vaccines are need of today, these vaccine prepare
and immune us for health tomorrow.
• Newer vaccines also required for some old diseases e.g. T.B.
HIV still we are not able to produced effective vaccine against
these disease.
• May be there is a need to find out new technique to develop
vaccine to make them more effective e.g. h.p.v. ,
1. K. PARK. , BOOK of social and preventive medicine,21st edition, bhanot
publication.
2. Plotkin , book on vaccine
3. http://www.niaid.nih.gov/topics/vaccines/understanding/pages/typesva
ccines.aspx
4. J.K. Sinha & S. Bhattacharya. A Text Book of Immunology. Academic
Publishers. p. 318. ISBN 978-81-89781-09-5. Retrieved 16 March 2012.
5. Kim W, Liau LM (2010). "Dendritic cell vaccines for brain
tumors". Neurosurg Clin N Am 21 (1): 139–
57.DOI:10.1016/j.nec.2009.09.005. PMC 2810429.PMID 19944973
6. http://www.cdc.gov/vaccinesafety/Vaccines/gbsfactsheet.html
7. History of Vaccines — A Vaccine History Project of The College of ...
• www.historyofvaccines.org/
8. Timelines — History of Vaccines
www.historyofvaccines.org/content/timelines/al (accessed on 5/7/2012)
9. "Monovalent" at Dorland's Medical Dictionary
10. Polyvalent vaccine at Dorlands Medical Dictionary
11. Vaccines: HOME page for Vaccines and Immunizations site
www.cdc.gov/vaccines
12 . anonymous, literature description of menctra vaccine, 2012
13. anonymous, literature description of prevnar vaccine, 2012
14.. anonymous, literature description of proqud vaccine, 2012
15 . anonymous, literature description of menctra vaccine, 2012
16. anonymous, literature description of flumist vaccine, 2012
17. anonymous, literature description of panenza vaccine, 2012
• Alarcon JB, Waine GW, McManus DP (1999). "DNA vaccines: technology
and application as anti-parasite and anti-microbial agents".Adv.
Parasitol. 42: 343–410.DOI:10.1016/S0065-308X(08)60152-
9.PMID 10050276.
• Robinson HL, Pertmer TM (2000). "DNA vaccines for viral infections: basic
studies and applications". Adv. Virus Res. 55: 1–74.DOI:10.1016/S0065-
3527(00)55001-5.PMID 11050940.
• Tang, D.; Devit, M.; Johnston, S.A.; Others, (1992). "Genetic immunization
is a simple method for eliciting an immune response". Nature356 (6365):
152–154.DOI:10.1038/356152a0.PMID 1545867.
• Barnes, Kirsty (2004-06-07). "First positive results for DNA-based flu
vaccine". in-PharmaTechnologist.
• "Fort Dodge Animal Health Announces Approval of West Nile Virus DNA
Vaccine for Horses". PR Newswire. 2005-07-18. Retrieved 2007-11-21.
• ^ "CDC and Fort Dodge Animal Health Achieve First Licensed DNA
Vaccine".CDC. 2005-07-18. Archived from the original on 2007-08-20.
Retrieved 2007-11-21.
• Wolff JA, Dowty ME, Jiao S, et al. (December 1, 1992). "Expression of
naked plasmids by cultured myotubes and entry of plasmids into T tubules
and caveolae of mammalian skeletal muscle". J. Cell. Sci.. 103 ( Pt 4) (4):
1249–59.PMID 1487500.
• Anderson RG, Kamen BA, Rothberg KG, Lacey SW (January
1992). "Potocytosis: sequestration and transport of small molecules by
caveolae". Science 255(5043): 410–
1.DOI:10.1126/science.1310359. PMID 1310359.
• Casares S, Inaba K, Brumeanu TD, Steinman RM, Bona CA (November
1997)."Antigen presentation by dendritic cells after immunization with
DNA encoding a major histocompatibility complex class II-restricted viral
epitope". J. Exp. Med. 186(9): 1481–
6.DOI:10.1084/jem.186.9.1481. PMC 2199124.PMID 9348305.
• http://www.aidsinfo.nih.gov/clinical-trials/, clinical trial on h.i.v. vaccine
(accessed on 03/07/2012)
• Vaccine trial on malaria,
www.who.int/vaccine_research/.../Session3_loucq_presentation.pdf
(accessed on 4/6/2012)
. Bock, R. (2010). "The give-and-take of DNA: horizontal gene transfer in
plants". Trends in Plant Science 15 (1): 11–22.DOI
:10.1016/j.tplants.2009.10.001. PMID 19910236.
Thank you
Cold Chain for Vaccine
Walk in Cold Room
Deep fridge (ILR) 300-500LTR
SMALL DEEP
FRIDGE
(140 LTR)
COLD BOXES
VACCINE
CARRIER
ICE
PACK

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Newer vaccines

  • 1.
  • 2. VACCINE 1. INTRODUCTION i. HISTORY. ii. CONCEPT OF VACCINE. iii. HOW IT WORKS. 2. NEED AND NECCESITY OF VACCINE. 3. NEWER VACCINE. i. RECENTALY DEVELOPED VACCINE ii. DEVELOPING VACCINE iii. FUTURE VACCINE
  • 4. • “A vaccine is a biological preparation that improves immunity to a particular disease.” • A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe. • The agent stimulates the body's immune system to recognize the agent as foreign, destroy it, and "remember" it, so that the immune system can more easily recognize and destroy any of these microorganisms if later encounters.
  • 5. • Vaccines can be prophylactic (e.g. to prevent or ameliorate the effects of a future infection by any natural or "wild" pathogen), or therapeutic (e.g. vaccines against cancer are also being investigated).
  • 7.  The Indian historian D.P. Agrawal suggests that the practice originated in India.[3] A religious rite having this effect was attributed to the physician Dhanvantari, founder of the Vedic tradition, in about 1500 BCE.[4].  The earliest written record of inoculation is thought to be found in 8th century India, when Madhav wrote the Nidāna, a 79-chapter book which lists diseases along with their causes, symptoms, and complications.[6] According to Donald R. Hopkins (2002), Madhav included a special chapter on smallpox (masūrikā) and described the method of inoculation to protect against smallpox.
  • 8. In the 18th century Dr. J.Z. Holwell wrote the most detailed account for the college of Physicians in London, describing not only inoculation, but also showing that the Indians knew that microbes caused Small Pox. Prior to vaccination, inoculation was practised, and brought to the West (EUROPE ) in 1721 by Lady Mary Wortley Montagu, from the Turkey
  • 9. First Story of Vaccine • Sometime during the 1770s Edward Jenner heard a milkmaid boast that she would never have the often-fatal , disfiguring disease smallpox, because she already had cowpox, which has a very mild effect in humans. In 1796, Jenner took pus from the hand of a milkmaid with cowpox, inoculated an 8-year-old boy with it, afterwards observing that the boy did not catch smallpox. Further experimentation demonstrated the efficacy of the procedure on an infant. Since vaccination with cowpox was much safer than smallpox inoculation. the latter, widely practiced in England & it banned in 1840. • Louis Pasteur generalized Jenner's idea by developing what he called a rabies vaccine. Edward Jennar
  • 10. MILE STONE of vaccine HISTORY
  • 11. 18th century • 1879 First vaccine for cholera • 1885 First vaccine for rabies by Louis Pasteur • 1890 First vaccine for tetanus • 1896 First vaccine for typhoid fever • 1897 First vaccine for bubonic plague 1796 First Vaccine for Smallpox ( the first vaccine ever developed ) 19th century
  • 12. 20th century • 1921 First vaccine for diphtheria • 1921 First vaccine for tuberculosis • 1926 First vaccine for pertussis (whooping cough) • 1932 First vaccine for yellow fever • 1937 First vaccine for typhus • 1945 First vaccine for influenza • 1952 First vaccine for polio by Jonas Salk • 1954 First vaccine for Japanese encephalitis • 1954 First vaccine for anthrax • 1957 First vaccine for adenovirus-4 and 7 • 1962 First oral polio vaccine • 1963 First vaccine for measles
  • 13. • 1967 First vaccine for mumps • 1970 First vaccine for rubella • 1974 First vaccine for chicken pox • 1977 First vaccine for pneumonia (Streptococcus pneumoniae) • 1978 First vaccine for meningitis ( Neisseria meningitides ) • 1981 First vaccine for hepatitis B (first vaccine to target a cause of cancer.) • 1985 First vaccine for Haemophilus influenzae type b (HiB) • 1992 First vaccine for hepatitis A • 1998 First vaccine for Lyme disease • 1998 First vaccine for rotavirus
  • 14. • 2003 First nasal vaccine for influenza approved in US (FluMist) • 2006 1ST vaccine for Human Papillomavirus. 21st century
  • 15. Term VACCINE AND TYPE The term vaccine derives from Edward Jenner's 1796 use of cow pox (Latin variola vaccinia, adapted from the Latin vaccīn, from vacca, cow), to inoculate humans, providing them protection against smallpox. • Types Vaccines are dead or inactivated organisms or purified products derived from them. There are several types of vaccines in use.[7] These represent different strategies used to try to reduce risk of illness, while retaining the ability to induce a beneficial immune response. So different type of vaccines are
  • 16. Killed - Some vaccines contain killed, but previously virulent, micro- organisms that have been destroyed with :- chemicals, heat, radioactivity or antibiotics. Attenuated— •Some vaccines contain live attenuated microorganism. Many of these are live viruses that have been cultivated under conditions that disable their virulent properties, or which use closely related but less dangerous organisms to produce a broad immune response. . •They typically provoke more durable immunological responses and are the preferred type for healthy adults. But they may get reverted to the virulent form and cause the disease.[8]
  • 17. Subunit :- • Rather than introducing an inactivated or attenuated micro- organism to an immune system (which would constitute a "whole-agent" vaccine), a fragment of it can create an immune response. • Examples include the subunit vaccine against Hepatitis B Virus that is composed of only the surface proteins of the virus. • Previously it extracted from the blood serum of chronically infected patients, but now produced by recombination of the viral genes into Yeast, • Other examples are Human Papillomavirus (HPV) that is composed of the viral major Capsid protein,
  • 18. Toxoid--Toxoid vaccines are made from inactivated toxic compounds that cause illness rather than the micro- organism. Examples of toxoid-based vaccines include tetanus and diphtheria. Toxoid vaccines are known for their efficacy. Conjugate – Certain bacteria have polysaccharide outer coats that are poorly immunogenic. By linking these outer coats to proteins (e.g. toxins), the immune system can be led to recognize the polysaccharide as if it were a protein antigen. This approach is used in the Haemophilus influenzae type B vaccine
  • 19. Carrier protein Polysaccharide linked to carrier protein Conjugate vaccine Bacteria Polysaccharide (sugar) coating Conjugation Conjugation is the process of attaching (linking) the polysaccharide antigen to a protein carrier (e.g. diphtheria or tetanus) that the infant’s immune system already recognises in order to provoke an immune response
  • 20. Recombinant DNA Vaccine • In recombinant DNA Vaccine, immunogenic part of antigen produced by recombinant DNA and that immunogenic part injected in body. • Like in Hep-B vaccine , H.P.V. vaccine Gene taken for Surface protein, of hep-b + yeast cell genome. kept in culture media (work as a production unit) Produce surface protein purified surface protein use as vaccine
  • 21. Valence ;- Vaccines may be monovalent (also called univalent) or multivalent (also called polyvalent). A monovalent vaccine is designed to immunize against a single antigen or single microorganism.[11] A multivalent or polyvalent vaccine is designed to immunize against two or more strains of the same microorganism, or against two or more microorganisms.[12] In certain cases a monovalent vaccine may be preferable for rapidly developing a strong immune response.[13]
  • 22. Live attenuated – measles, mumps, rubella, oral polio, BCG, yellow fever, varicella Inactivated – influenza, rabies, anthrax, IPV, pertussis Inactivated toxins – tetanus, diphtheria Subcellular fraction – pneumococcal, Hib, Men C Genetically engineered – Hepatitis B Examples of Vaccines
  • 23. The efficacy of these vaccine. • the disease itself (for some diseases vaccination performs better than for other diseases) • the strain of vaccine (some vaccinations are for different strains of the disease)[4] • whether one kept to the timetable for the vaccinations (see Vaccination schedule) • some individuals are "non-responders" to certain vaccines, meaning that they do not generate antibodies even after being vaccinated correctly • other factors such as ethnicity, age, or genetic predisposition.
  • 25.
  • 26. Toxoids Bacterial vaccines (in general) Viral vaccines (in general) BCG Vaccines administered orally or intra-nasally • Antitoxin neutralising antibodies • Multiple antibodies (neutralisation,opsonisation, complement activation ...) • Multiple antibodies (neutralisation essentially) which act before the viruses penetrate the cell + cytotoxic T cells • Cellular mediated immunity • Humoral immunity + mucosal immunity (IgA)
  • 27. NEED AND NECCESITY OF VACCINE Always said “prevention is better then cure”  Vaccines are the important tool in preventive medicine as well as in public health.  vaccines are the one of the important tool to control the emergence of disease ,stop that to make public health problem.e.g. swine flu pandemic  Vaccines is work at very grass root level and compare to treatment it become cost effective then other measures e.g. Small Pox , Polio , Measles are good examples
  • 28. NEWER VACCINE 1. RECENTALY DEVELOPED VACCINE 2. DEVELOPING VACCINE 3. FUTURE OF VACCINES
  • 29. SINGLE ANTIGEN VACCINE 1. Prevnar (pneumococcal conjugate vaccine) 2002 2. Flumist (1st live attenueted influenza vaccine ) 2003 3. 1st killed Influenza vaccine 2004 4. Menatra (new meningococcal vaccine ) 2005 5. Rotateq (Rota vaccine) 2006 6. HPV vaccine (Gardasil)2006 7. Varivax (for chicken pox)2007 8. Flumist nasal vaccine of 1st live attenueted influenza vaccine 9. Rotarix (rota virus vaccine) 2008 10. Influenza-A (H1N1) 2009
  • 30. NAME OF VACCIN E APROVE D BRAND AGE INDICATIONS & USAGE DOSAGE AND ADMINISTRATION Pneumoco ccal conjugate vaccine Prevnar 13 1. In children 6 weeks through 5 years of age (prior to the 6th birthday), Active immunization for invasive disease caused By streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F. Otitis media caused by Streptococcus pneumoniae serotypes 4, 6b, 9v, 14, 18c, 19f, And 23f. The four-dose immunization series Consists of a 0.5 ml intramuscular injection administered at 2, 4, 6, and 12- 15 months of age. (2.3) 2. In adults 50 years of age and older Active immunization for invasive disease caused By streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F. Adults 50 years and older: a single dose. (2.6) C/I 1. Allergy to contents 2. Premature baby 3.Immunocompromised
  • 31. INDICATION AND USAGE :- age against Influenza disease caused by Influenza Virus subtypes A and type B DOSAGE & ADMINISTRATION :- CONTRAINDICATIONS:- Hypersensitivity to eggs, egg proteins, gentamicin, gelatin, or arginine, or life-threatening reactions to previous influenza vaccination. (4.1) • Concomitant aspirin therapy in children and adolescents. 900RS.
  • 32. INDICATIONS AND USAGE :-Menactra vaccine is indicated for active immunization to prevent invasi ve meningococcal disease caused by N meningitidis serogroups A, C, Y and W-135. Menactra is approved for use in individuals 9 months through 55 years of age. Menactra vaccine does not prevent N meningitidis serogroup B disease. (1) DOSAGE AND ADMINISTRATION A 0.5 mL dose for intramuscular injection. • Children 9 through 23 months of age: Two doses, three months apart. • Individuals 2 through 55 years of age: A single dose. CONTRAINDICATIONS Severe allergic reaction (eg, anaphylaxis) after a previous dose of a meningococcal capsular polysaccharide-, diphtheria toxoid- or CRM197-containing vaccine, or to any component of Menactra vaccine. (4)
  • 33. • Rota shield:- in 1998, a rotavirus vaccine (rot shield, by Wyeth) was licensed for use in the united states, but withdrawal from market due to increased incidence of intussusception,in 1999-2000. • Rotarix :- • ROTARIX is indicated for the prevention of rotavirus gastroenteritis caused by G1 and non-G1 types (G3, G4, and G9), • ROTARIX is approved for use in infants 6 weeks to 24 weeks of age dose 1 ml, gap between 2 dose should be 1 month • CONTRAINDICATIONS :- • congenital malformation of the gastrointestinal tract, • History of intussusception • History of Severe Combined Immunodeficiency Disease (SCID).
  • 34. • :- it is a live, oral pentavalent vaccine that contains five rota viruses types. • Dosage forms and strengths :- Rota-teq, 2 mL for oral use, is a ready-to-use solution of live reassortant rotaviruses, containing G1, G2, G3, G4 and P1A[8] • Age - Administered as a 3-dose series to infants between the ages of 6 to 32 weeks. The first dose of rotateq should be administered between 6 and 12 weeks of age, with the subsequent doses administered at 4- to 10-week intervals. The third dose should not be given after 32 weeks of age. • Contraindications - Hypersensitivity, History of Intussusceptions , Severe Combined Immunodeficiency Disease. • 1250/- ROTATEQ
  • 35. INDICATIONS AND USAGE :- girls and women 9 through 26 years of age for the prevention of the following caused by HPV : - Cervical, vulvar, vaginal, and anal cancer & Genital warts (condyloma acuminata) boys and men 9 through 26 years of age for the prevention of the - Anal cancer & Genital warts (condyloma acuminata). DOSAGE AND ADMINISTRATION -- 0.5-mL suspension for intramuscular injection at the following schedule: 0, 2 months, 6 months. (2.1) DOSAGE FORMS AND STRENGTHS :- 0.5-mL suspension for injection as a single-dose vial and prefilled syringe. CONTRAINDICATIONS--Hypersensitivity, including severe allergic reactions to yeast (a vaccine component), or after a previous dose of GARDASIL. 3100/-
  • 36. • INDICATIONS AND USAGE :- VARIVAX is indicated for vaccination against Varicella in individuals 12 months of age and older. The duration of protection of VARIVAX is unknown; however, long-term efficacy studies have demonstrated continued protection up to 10 years after vaccination. • DOSAGE AND ADMINISTRATION: (FOR SUBCUTANEOUS ADMINISTRATION ) • Children :- 12 months to 12 years of age should receive a 0.5-mL dose administered subcutaneously. If a second 0.5-mL dose is administered, it should be given a minimum of 3 months later. • Adolescents and Adults :-Adolescents and adults 13 years of age and older should receive a 0.5-mL dose administered S.C. at elected date and a second 0.5-mL dose 4 to 8 weeks later. • CONTRAINDICATION :- Individuals with leukemia, lymphomas of any type, or other malignant neoplasm affecting the bone marrow or lymphatic systems. 1500/-
  • 37. • Both vaccines are for influenza A H1N1 virus but basic difference is panenza is non-adjuvant and humenza is adjuvant vaccine, so humenza need less strenght of vaccine. • STORAGE:- • Store in a refrigerator between +2°C and +8°C. • DISCARD opened vials within 7 days (opened vials can be used for a maximum of 7 days) if kept between +2°C and +8°C.
  • 39. INSTRUCTIONS FOR VACCINE ADMINISTRATION: • It is necessary to closely follow good practices of asepsis at each step of handling. • Before injection the vaccine should be allowed to reach room temperature by gently swirling the vial between hands (not more than 5 minutes). • Shake before each use. • Each dose of vaccine must be withdrawn with a new syringe and needle suitable for IMinjection ROUTE OF ADMINISTRATION: • The vaccine will be injected into a muscle.
  • 40. 1. Pediarix ( DTaP + IPV + HEP-B )2004 2. Proquad ( MMR + VARIVAX ) 2006
  • 41. • Diphtheria and Tetanus Toxoid and Acellular Pertussis Adsorbed, Hepatitis B (Recombinant) and Inactivated Poliovirus Vaccine Combined]. • Recommended Schedule & DOSE : The primary immunization series for PEDIARIX is 3 doses of 0.5 mL, given intramuscularly, at 6- to 8-week intervals (preferably 8 weeks). The customary age for the first dose is 2 months of age, but it may be given starting at 6 weeks of age. • Contraindications:- Hypersensitivity to any component of the vaccine, including yeast, neomycin, and polymyxin-B, is a contraindication
  • 42. • INDICATIONS AND USAGE :- ProQuad is a vaccine indicated for active immunization for the prevention of measles, mumps, rubella, and varicella in children 12 months through 12 years of age. (1) • DOSAGE AND ADMINISTRATION :- A 0.5-mL dose for subcutaneous injection only. The first dose is usually administered at 12 to 15 months of age. A second dose, if needed, is usually administered at 4 to 6 years of age. • CONTRAINDICATIONS:- History of anaphylactic reaction to neomycin or hypersensitivity to gelatin or any other component of the vaccine. Primary or acquired immunodeficiency states. Family history of congenital or hereditary immunodeficiency.
  • 43.
  • 44. HIV VACCINE In 1984, after the confirmation of the etiological agent of AIDS by scientists at the U.S. National Institutes of Health and the Pasteur Institute, the United States Health and Human Services Secretary Margaret Heckler declared that a vaccine would be available within two years. But still it is a dream.
  • 45. The ineffectiveness of previously developed vaccines primarily stems from two related factors. • First, HIV is highly mutable. Because of the virus' ability to rapidly respond to selective pressures imposed by the immune system, • Second, HIV isolates are themselves highly variable. HIV can be categorized into multiple clades and subtypes with a high degree of genetic divergence. Therefore, the immune responses raised by any vaccine need to be broad enough to account for this variability. Any vaccine that lacks this breadth is unlikely to be effective.
  • 46. Challenges in HIV Vaccine Research • Viral Genetic Diversity: HIV is not just one specific virus. • Immune Protection: We don’t know what immune responses are needed, or how strong they need to be. • Neutralizing Antibody: Difficult to generate broadly neutralizing antibodies. • Vaccine Testing: Slow process, very expensive
  • 47. …but on the Brightside… • Precedent from animal studies: Long- term control of infection in vaccinated monkeys • Immune control of HIV-1: Infected individuals control infection • Vaccine Trials: In progress
  • 48. Vaccine Vector Platform • Vaccine Approach: Genetic engineer, doctors characterize and optimize a viral vector system that can be used to deliver HIV antigen(s) to antigen presenting cells (APCs) and that could also improve immune responses to induce long- term immunological memory. Approach are-- • Viral Vectors – HSV-based Amplicon Vector – Recombinant Adenovirus Type 5 Vector – Bacteriophage Lambda Vector
  • 49. • A June 2005 study estimates that $682 million is spent on AIDS vaccine research annually.[26] • Economic issues with developing an AIDS vaccine include the need for advance purchase commitment because after an AIDS vaccine has been developed, governments and NGOs may be able to bid the price down to marginal cost.[27]
  • 50. VaxGen USA VaxGen Thai Trial Step Trial Thai Trial Trial start/end Trial analysis/results First correlates 1990 1995 2000 2005 2010 1 year 1 year 6 months 16 months HVTN 505 Enrollment in process
  • 51. Timeline of HIV Vaccine Efficacy Trials From 1990 to 2010 VaxGen USA VaxGen Thai Trial Step Trial Thai Trial Trial start/end Trial analysis/results First correlates 1990 1995 2000 2005 2010 1 year 1 year 6 months 16 months HVTN 505 Enrollment in process Recombinant gp120 No Efficacy
  • 52. Timeline of HIV Vaccine Efficacy Trials From 1990 to 2010 VaxGen USA VaxGen Thai Trial Step Trial Thai Trial Trial start/end Trial analysis/results First correlates 1990 1995 2000 2005 2010 1 year 1 year 6 months 16 months HVTN 505 Enrollment in process Ad5 Gag Pol Nef T cell vaccine No Efficacy
  • 53. Classification of all theoretically possible HIV vaccines • Any theoretically possible HIV vaccines must inhibit or stop the HIV virion replication cycle.[28] So, the targets of the vaccine are the following phases of the HIV virion cycle: • Phase I. Free state • Phase II. Attachment • Phase III. Penetration • Phase IV. Uncoating • Phase V. Replication • Phase VI. Assembling • Phase VII. Releasing • So, the possible approaches for the HIV vaccine are the following (in the bracket specified the Phases were it is possible to do).
  • 54. • Filtering virions from blood (Phase I • Approaches to destroying or damaging the virion or its parts (Phase I-VII) • By nature of method: – Physical methods (Phase I-VII) – Chemical and biological methods (Phase I-VII) • By damaging target of the HIV virion structure: – Damaging the Docking Glycoprotein gp120 (Phase I-III, VI, VII) – Damaging the Transmembrane Glycoprotein gp41 (Phase I-III, VI, VII) – Damaging the virion matrix (Phase I-III, VI, VII) – Damaging the virion Capsid (Phase I-III, VI, VII) – Damaging the Reverse Transcriptase (Phase I-VII) – Damaging the RNA (Phase I-VII)
  • 55. • Blocking the replication (Phase I). • Inhibiting process of phases (drugs already used for this approach). • Inhibiting the functionality of infected cells (Phase VI- VII). • Approaches to catching the virion (Phase I- III, VI, VII).
  • 56. Future work • First, greater translation between animal models and human trials must be established. • Second, new, more effective, and more easily produced vectors must be identified. • Finally, and most importantly, there must arise a robust understanding of the immune response to potential vaccine candidates. • A vaccine, SAV001, that has had success in animal subjects began Phase 1 human trials in London, Ontario in 2011.[30]
  • 57. Transgenic plants • Transgenic plants can be a convenient and efficient way to obtain HIV vaccine. Plant-based vaccines, which are easy to produce and administer, and require no cold chain for their heat stability are, in principle, suited to such a strategy. More recently, it has been shown that even highly immunogenic, enveloped plant-based vaccines can be produced at a competitive and more efficient rate than conventional strategies
  • 59. Why a vaccine? Data as of the end of 2008, WHO
  • 60. 61 Malaria vaccine community goal • Strategic Goal: To develop an 80% efficacious malaria vaccine by 2025 that would provide protection for at least four years • Landmark goal: To develop and license a first-generation malaria vaccine that has protective efficacy of more than 50% against severe disease and death and lasts longer than one year Malaria Vaccine Technology Roadmap http://www.malariavaccineroadmap.net/ P. vivax and Pf / Pv transmission-blocking vaccines
  • 61. Vaccines Under Development • A completely effective vaccine is not yet available for malaria, although several vaccines are under development. SPf66 was tested extensively in endemic areas in the 1990s, but clinical trials showed it to be insufficiently effective. • Other vaccine candidates, targeting the blood-stage of the parasite's life cycle, have also been insufficient on their own. • Several potential vaccines targeting the pre-erythrocytic stage are being developed, with RTS,S/ ASO1 showing the most promising results so far.
  • 62. RTS,S/AS01 (commercial name: Mosquirix) • which started Pivotal Phase III evaluation in May 2009. • It is designed not for travellers but for children resident in malaria-endemic areas who suffer the burden of disease and death related to malaria. • The RTS,S vaccine was engineered using genes from the outer protein of Plasmodium falciparum malaria parasite and a portion of a hepatitis B virus plus a chemical adjuvant to boost the immune system response.
  • 63. Result • In October 2011 the group reported first findings from the Phase III trial of RTS,S indicating that 46% of 15,460 inoculated infants and children were protected for 15 months.[5][6][7]
  • 64. Vaccine development strategies for the future • The development of a vaccine of therapeutic and protective benefit against the malaria parasite requires a novel approach as to date there are no vaccines available that effectively target a parasitic infection. • The focus so far has been predominately on the use of sub-unit vaccines. • The use of live, inactivated or attenuated whole parasites is not feasible and therefore antigenic particles, or subunits, from the parasite are isolated and tested for immunogenicity i.e. the ability to elicit an immune response.
  • 65. • The majority of subunits tested have been discussed above and are frequently combined with adjuvants and specialised delivery systems to increase the very variable level of immune response. • The most recent advances in the field of sub-unit vaccine development include the use of DNA vaccination.
  • 67. • Despite decades of effort by many scientists to develop a vaccine for dengue, no licensed vaccine is available. The problem begins with the virus itself (or really, the viruses). Dengue is caused by infection with any of four closely related dengue viruses, and a successful dengue vaccine must offer immunity against all four. • the Division of Vector-Borne Diseases (DVBD) at Fort Collins, CO, have developed a dengue vaccine candidate that is now being clinically evaluated in the United. States and Colombia for safety and efficacy • The first human Phase-I trial showed that the vaccine was safe, well tolerated, and produced antibody levels that should protect against all four dengue viruses. • Because of these encouraging results, a Phase-II clinical trial to assess immunogenicity (ability to provoke an adequate immune response) will begin in 2012.
  • 68. • A successful Phase-II trial would be followed by Phase-IIb or Phase-III trials to determine efficacy at a much larger scale. Clearly, development and testing of a human vaccine requires many steps. • This technology has been awarded multiple U.S. and international patents. CDC’s dengue vaccine team has partnered with Inviragen, Inc., a Colorado-based vaccine manufacturer. • Inviragen is manufacturing the vaccine, named DENVax, and is conducting clinical development and testing of the vaccine for human use. The goal is to provide a safe, effective, and affordable dengue vaccine
  • 70. In brief • A vaccine containing ICRC bacilli (which are cultivable leprosy derived mycobacteria probably belonging to M. avium intracellulare complex) was prepared in 1979 at the Cancer Research Institute, Mumbai[12]. • Studies, both on humans and animals, show that the ICRC bacilli exhibit antigenic cross-reactivity with M.leprae with reference to both B and T cell antigens
  • 71.
  • 72.
  • 73. (iii) FUTURE OF VACCINES 1. Therapeutic cancer vaccine 2. Biodefense and special pathogen vaccines
  • 74. 1. Therapeutic cancer vaccine . A number of innovative vaccines are also in development and in use: 1. Dendritic cell vaccines combine dendritic cells with antigens in order to present the antigens to the body's white blood cells, thus stimulating an immune reaction. These vaccines have shown some positive preliminary results for treating brain tumors.[9]
  • 75. 2. Vaccine for non infectious disease •T-cell receptor peptide vaccines are under development for several diseases using models of Valley Fever, stomatitis, and atopic dermatitis. These peptides have been shown to modulate cytokine production and improve cell mediated immunity.
  • 76. 3. Synthetic Vaccines •Targeting of identified bacterial proteins that are involved in complement inhibition would neutralize the key bacterial virulence mechanism.[10] •While most vaccines are created using inactivated or attenuated compounds from micro-organisms, synthetic vaccines are composed mainly or wholly of synthetic peptides, carbohydrates or antigens that will produced more strong immunity and can be expected to stay longer or life time.
  • 78. INTRODUCTION DNA vaccine is DNA sequence used as a vaccine. This DNA Sequence code for antigenic protein of pathogen. As this DNA inserted into cells it is translated to form antigenic protein. As this protein is foreign to cells , so immune response raised against this protein. In this way ,DNA vaccine provide immunity against that pathogen.
  • 79. HISTORY In 1990, University of Wisconsin, Jon Wolff found that injection of DNA plasmids produce a protein response in mice. In 1993, Merck Research Laboratories, Dr. Margaret Liu found that intramuscular injection of DNA from influenzae virus into mice produced complete immune response In 1996, trials involving T-cell lymphoma, influenzae & herpes simplex virus were started
  • 80. DNA vaccines Vs Traditional vaccines  Uses only the DNA from infectious organisms.  Avoid the risk of using actual infectious organism.  Provide both Humoral & Cell mediated immunity  Refrigeration is not required  Uses weakened or killed form of infectious organism.  Create possible risk of the vaccine being fatal.  Provide primarily Humoral immunity  Usually requires Refrigeration. DNA vaccines Traditional vaccines
  • 81. HOW DNA VACCINE IS MADE Viral gene Expression plasmid Plasmid with foreign gene Recombinant DNA Technology
  • 85. METHODS OF DELIVERY Syringe delivery:- Either intramuscularly or Intradermally
  • 86. Contd.. Gene gun delivery:- Adsorbed plasmid DNA into gold particles Ballastically accelerated into body with gene gun.
  • 87. ADVANTAGES Elicit both Humoral & cell mediated immunity Focused on Antigen of interest Long term immunity Refrigeration is not required Stable for storage
  • 88. DISADVANTAGES Limited to protein immunogen only Extended immunostimulation leads to chronic inflammation Some antigen require processing which sometime does not occur
  • 89. CURRENT CLINICAL TRIALS June 2006,DNA vaccine examined on horse. Horse acquired immunity against west nile viruses. August 2007,DNA vaccination against multiple Sclerosis was reported as being effective.
  • 90. SAFETY ISSUE WITH DNA VACCINE
  • 91. • Genetic Toxicity • Integration of DNA vaccine into host Genome can cause • Insertional mutagenesis • Chromosome instability • Turn ON Oncogenes • Turn OFF Tumor suppressor genes • Over Expression of DNA vaccine • Generation of Autoimmune diseases • Autoimmune Myositis • Anti DNA Antibodies • Autoimmune diseases • Antibiotic Resistance • Plasmid used is resistance to antibiotics for selection
  • 92. CONCLUSION DNA vaccines are in their early phase. There are no DNA vaccines in market at present. But this just the beginning .DNA vaccines are going to be the vaccines of next generation.
  • 93. Conclusion • Discovery of newer vaccine is a continuous process and it is never going to stop. • Newer vaccines are need of today, these vaccine prepare and immune us for health tomorrow. • Newer vaccines also required for some old diseases e.g. T.B. HIV still we are not able to produced effective vaccine against these disease. • May be there is a need to find out new technique to develop vaccine to make them more effective e.g. h.p.v. ,
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  • 100. Cold Chain for Vaccine
  • 101. Walk in Cold Room
  • 102. Deep fridge (ILR) 300-500LTR