Newer

Vaccines
for
Clinical Use
Dr.T.V.Rao MD
 What is a “Vaccine”
 The term vaccine
derives from Edward
Jenner's 1796 use of
the term cow pox (Latin)
variola vaccinæ,
adapted from the Latin
vaccīn-us, from vacca
cow), which, when
administered to
humans, provided them
protection against
smallpox
 Vaccine- Definition
 A vaccine is any preparation intended to
produce immunity to a disease by
stimulating the production of antibodies.
Vaccines include, for example,
suspensions of killed or attenuated
microorganisms, or products or derivatives
of microorganisms. The most common
method of administering vaccines is by
injection, but some are given by mouth or
nasal spray.
 Dr Jenner and Cow Pox
 THE MODERN SCIENCE OF
IMMUNOLOGY HAD ITS
BEGINNINGS IN 1798 , WHEN
THE ENGLISH PHYSICIAN
EDWARD JENNER PUBLISHED A
PAPER IN WHICH HE
MAINTAINED THAT PEOPLE
COULD BE PROTECTED FROM
THE DEADLY DISEASE
SMALLPOX BY THE PRICK OF A
NEEDLE DIPPED IN THE PUS
FROM A COWPOX BOIL .
Historical Picture of Vaccination
 Vaccine stimulates Immune
System
 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 that it later
encounters
 Preparation of Vaccines
a. Liveattenuated organisms which have been passed
repeatedly in tissue culture or chick embryos so that
they have lost their capacity to cause disease, but
retained an ability to induce antibody response, such
as polio (Sabin), measles, rubella, mumps, yellow fever,
BCG, typhoid and plague.
b. Inactivated or killed organisms which have been killed
by heat or chemicals but retain and ability to induce
antibody response. They are generally safe but less
efficacious than live vaccines and require multiple
doses; e.g. polio (Salk), influenza, rabies and Japanese
encephalitis.
 Preparation of Vaccines
c. Cellular fractions: usually polysaccharide fraction
of the cell wall of a disease causing organism,
such as pneumococcal pneumonia or
meningococcal meningitis
d. Recombinant vaccines: produced by methods in
which specific DNA sequences are inserted by
molecular engineering techniques, e.g. DNA
sequences spliced to vaccinia virus grown in cell
culture to produces an effective influenza vaccine,
and Hepatitis B vaccine by similar methods.
 Passive Immunity
“Vaccination”
Toxoids or antisera: are modified toxins made non-toxic to
stimulate formation of an antitoxin, such as those produced to
protect against toxins of tetanus, diphtheria, botulism, gas
gangrene, snake and scorpion venom.

Immune globulin: An antibody containing solution derived from

human blood in the form of pooled plasma, used primarily for
immunity for passive immunization such as for immuno-
compromised persons e.g. smallpox response groups.

Antitoxin: is an antibody derived from serum of animals after

stimulation with specific antigens and used to provide passive
immunity in humans.
Life cycle of Vaccination
 Timeline of Vaccines
 18th century
 1796 First vaccine for smallpox,
first vaccine for any disease
 19th century
 1882 First vaccine for rabies
 Timeline of Vaccines
 20th century
 1932 First vaccine for yellow fever
 1945 First vaccine for influenza
 1952 First vaccine for polio
 1954 First vaccine for
Japanese encephalitis
 1957 First vaccine for adenovirus-4 and 7
 1962 First oral polio vaccine
 1964 First vaccine for measles
 1967 First vaccine for mumps
 Timeline of Vaccines
 1970 First vaccine for rubella
 1974 First vaccine for chicken pox
 1977 First vaccine for pneumonia
 1978 First vaccine for meningitis
 1981 First vaccine for hepatitis B
 1992 First vaccine for hepatitis A
 1998 First vaccine for rotavirus
 World Health Organisation
Reports
 "Nearly nine million children under 14
years of age die every year from
infectious disease. And at least a third
of them could be saved if existing
vaccines were more widely used, but
the rest only if suitable new vaccines
were developed..."
Vaccines use in the world
 For the past two decades, in most developing
countries, vaccination restricted only to the
initial EPI vaccines
 Where-as in most developed countries,
several new vaccines such as Hep B, Hib,
meningococcal, pneumococcal, were
gradually added to the initial EPI vaccines,
 Thus widening the gap in protection against
infectious diseases between the rich and the
poor
Number of Childhood Vaccines Routinely
Used in Developing and Established
Market Countries Acell pertussis
13 Pneumococcal *
meningoccoal C*
12 Established Market

11 Developing Countries

10 Varicella
9 Haemophilus Influenzae
Measles Hepatitis B
8 Mumps
Rubella
7 DPT
6 Poliomyelitis
Hepatitis B**
5
Measles
1975
DPT 1980 1985 1990 1995 2000
Poliomyelitis
BCG

*Estimated future use

**Used in ~ 50% of global birth cohort
 Newer
Vaccines
Stages of Review and Regulation
for Devloping Vaccines
 Phase 1 - Safety, immunogenicity (prelim)
 Phase 2 – Immunogenicity, Safety, Dose
Ranging
 Phase 3 – Efficacy, Safety, Immunogenicity
 BLA – Pre-clinical and clinical data to support
approval, inspection
 Phase 4 – Inspection, Safety, Efficacy, Lot
Release
 BLA-Supplement (post-approval changes)
 Stages of Vaccine
Development
 Vaccine development
proceeds through
discovery, process
engineering, toxicology
and animal studies to
human Phase I, II, and
III trials. The process
can take more than 10
years, depending on
the disease.
Stage I Development
 The human trials
focus initially on
safety, involving small
groups of people
 Stage II of Development
 Progress to moderate-
sized "target"
populations (persons
close to the age and
other characteristics for
whom the vaccine is
intended) to determine
both safety and the
stimulation of immune
response.
Stage III of Development
 Finally to large target
populations to
establish whether a
vaccine actually
prevents a disease as
intended (efficacy)
 An ideal Vaccine should be
….
 Good immune response
 Both Cell Mediated Immunity and antibody responses.
 Immunity is long lived
 Single dose
 Safety
 Danger of reversion to virulence, or Severe disease in immunocomprised
 Stability
 Organisms in the vaccine must remain viable in order to infect and replicate in
the host
 Vaccine preparations are therefore very sensitive to adverse storage conditions
 Maintenance of the cold chain is very important.
 Expense
 Cheap to prepare
 Causes of death in
children less than 5 years old

20%
ARI
Diarrhea
VPD
Perinatal
Other
20%

19%

13%
The Global Burden of Disease
Murray and Lopez, editors
Total - 12.8 million
 New approved vaccines
 A number of new vaccines with major
potential for controlling infectious diseases
have just been licensed or are at
advanced stages of development. Among
the illnesses targeted are rotavirus
diarrhoea, pneumococcal disease, and
cervical cancer (as caused by human
papillomavirus), which together kill more
than a million people each year, most of
them in developing countries.
Bacterial Meningitis kills several in
Developing world
 Haemophilus influenzae type b (Hib)
 30% -50% of bacterial meningitis
 Pneumococcus
 25- 35% of bacterial meningitis
 Meningococcus
 25 - 35% of bacterial meningitis (except
during epidemics)
Hib meningitis and pneumonia burden

Estimated rate (children<5)

> 200/100,000
100-200/100,000
45-100/100,000
< 45/100,000
 Meningococcal Meningtis
Threat to AFRICA
 The African "meningitis belt" - which includes all
or part of 21 countries stretching south of the
Sahara desert from Senegal to Ethiopia - is the
site of frequent epidemics, usually caused by
serogroup A meningitis. Over the past decade
more than 700 000 cases have been reported.
Roughly 10-20 % of persons infected die, and
one out of five survivors is likely to suffer from a
permanent disability such as hearing loss,
mental retardation, or paralysis.
Status of vaccine development
Polysaccharide vaccines (vaccines made from
complex sugars taken from the outer coats of
the Men bacterium) are currently in use, but are
not very effective at protecting young children,
do not create long-lasting immunity, and do not
confer a "herd effect". Because of these
shortcomings, immunization with polysaccharide
vaccines is usually undertaken only after the
onset of an epidemic.
 Rotavirus Diarrhoeas
Acute diarrhoea is
responsible for nearly
1.9 million deaths per
year in children under
age five. Rotavirus is
responsible for as
much as one fourth of
these casualties, almost
all of which occur in
developing countries.
Global Density of Rota viral
Infections
Status of vaccine
development:
 RotaRix, a vaccine developed
by GlaxoSmithKline (GSK),
against rotavirus diarrhoea is
now licensed in many
countries. In addition to being
available on the private market
in these countries, it has now
been introduced in the public
sector immunization
programmes of Brazil, El
Salvador, Mexico, Panama
and Venezuela. . A Phase III
trial is also under way in South
Africa and Malawi.
 Merck & Co.’s RotaTeq
 RotaTeq, introduced in 2006
for kids aged 2 months, 4
months, and 6 months, is a
highly promising protection
against the highly contagious
disease –Rotavirus, says
CDC.
 The Centers for Disease
Control and Prevention (CDC)
believes that the level of
protection provided by the
vaccine is much stronger than
they originally anticipate
 Pneumococcal disease
and Vaccination
 Acute lower
respiratory infections
are responsible for
close to two million
deaths per year and a
large proportion of
these are caused by
Streptococcus
pneumoniae
(pneumococcus).
Prevenar contain seven
serotypes
 A seven-valent conjugate
vaccine called Prevnar (or
Prevenar) is designed to act
against seven strains of
pneumococcal disease. It
has been developed by
Wyeth Vaccines and is
licensed in the United States
and over 70 other countries,
but does not include two
serotypes (types 1 and 5)
that cause a high percentage
of pneumococcal illness in
developing countries. (
 Nine-valent conjugate vaccine a
Succesul trial in Gambia
 Wyeth Vaccines has also
completed evaluation of a
nine-valent conjugate
vaccine, including serotypes
1 and 5. A Phase III trial of
the vaccine involving 40 000
people was completed in
South Africa in 2002, and a
Phase III trial with 17 437
subjects was concluded in
the Gambia in 2004.
 Challenges to identify
Pneumococcal infections
 It can be difficult to establish the extent of
pneumococcal disease as developing countries
often lack the laboratory facilities, expertise, and
resources to do so. As a result, public health
decision-makers are often unaware of the
prevalence of the disease and of the toll it
exacts in death and disability. Because of the
scarcity of data from developing countries, there
is concern over the appropriate serotype
valence for developing countries
 Human papillomavirus (HPV)

 Sexually transmitted HPV is the major

cause of cervical cancer, the most
common cause of cancer deaths among
women in developing countries. About
5,00 000 cases occur each year, 80% of
them in developing countries. Cervical
cancer kills some 240 000 women
annually.
 HPV 16 and 18 major types
causing Carcinoma cervix
 HPV types 16 and 18 cause around 70%
of HPV cervical cancers globally, but the
vaccines in development will not cover the
30% of cancers attributed to other HPV
types. Because these other types are
numerous and individually only contribute
a small percentage, significantly
expanding vaccine coverage against them
may present technical challenges for
manufacturers.
 Two types of vaccines for Human
Papilloma virus prevention
 Bivalent human papillomavirus vaccine (HPV2) licensed
for use in females
 Either HPV2 or quadrivalent HPV vaccine (HPV4) used
for females ages 19-26 years
 Quadrivalent human papillomavirus vaccine (HPV4)
licensed for use in males
 HPV4 may be administered to males aged 9 through 26 years
to reduce their likelihood of acquiring genital warts.
 GARDASIL
 Gardasil, an HPV vaccine recently
licensed by Merck, covers four types of
HPV, including the cancer-causing types
16 and 18 and types 6 and 11 for non-
cancerous genital warts. A second
vaccine, developed by GSK, covers HPV
types 16 and 18 alone
 GARDASIL
 GARDASIL is the only human papillomavirus
(HPV) vaccine that helps protect against 4 types
of HPV. In girls and young women ages 9 to 26,
GARDASIL helps protect against 2 types of HPV
that cause about 75% of cervical cancer cases,
and 2 more types that cause 90% of genital
warts cases. In boys and young men ages 9 to
26, GARDASIL helps protect against 90% of
genital warts cases.
How long vaccination is effective
and
Ideal age for Vaccination
 The duration of the immunity conferred by the
vaccines is not yet known, and only time and
follow up studies will provide this critical
information... Because HPV is spread by sexual
contact, and the high-risk years for infection are
roughly from ages 18 to 25, the best subjects for
vaccination will likely be pre-adolescents or
adolescents, unlike for traditional vaccination
programmes, which are aimed mostly at infants
and pregnant women.
 FDA approves Gardasil
 In October 2009, the
FDA approved the
use of GARDASIL in
boys and young
men ages 9 to 26 to
protect against 90%
of genital warts
cases.
 Meningococcal meningitis A
Vaccine (Men A)
 Polysaccharide vaccines (vaccines made from complex
sugars taken from the outer coats of the Men bacterium)
are currently in use, but are not very effective at
protecting young children, do not create long-lasting
immunity, and do not confer a "herd effect" - that is, do
not prevent spread of the disease in non-vaccinated
people through reduction of the carriage of the infectious
agent by vaccinated people during epidemics
 Because of these shortcomings, immunization with
polysaccharide vaccines is usually undertaken only after
the onset of an epidemic.
 Better Vaccine for
Meningococcal Infection
 To provide greater and more efficient
protection, a public-private effort called the
Meningitis Vaccine Project (MVP) is
developing a Men A conjugate vaccine.
This vaccine is intended to have long-
lasting effect, to create immunity in infants,
and to allow protection to be conferred in
advance through mass immunization
programmes
 Meningococcal vaccine
 Meningococcal conjugate vaccine (MCV4) if
preferred for adults aged 55 years or younger;
meningococcal polysaccharide vaccine
(MPSV4) is preferred for adults aged 56 years
or older.
 Revaccination with MCV4 after 5 years is
recommended for adults previously vaccinated
with MCV4 or MPSV4 who remain at increased
risk for infection.
 Other Vaccines in
Meningococcal Infection
 Other conjugate vaccines, including a
heptavalent vaccine (DTP Hep B Hib)
covering Sero groups A, and C, are being
developed by the private sector; and a
tetravalent vaccine has recently been
licensed by Sanofi-Pasteur in the United
States and Canada.
 Zoster vaccine
 The zoster vaccine licensed in the United States
(ZOSTAVAX®, Merck & Co., Inc.) is a
lyophilized preparation of the Oka/Merck strain
of live, attenuated VZV, the same strain used in
the varicella vaccines (VARIVAX®,
PROQUAD®). The Oka strain was isolated in
Japan in the early 1970s from vesicular fluid
from a healthy child who had varicella; the strain
was attenuated through sequential propagation
in cultures of human embryonic lung cells,
embryonic guinea-pig cells, and human diploid
cells (WI-38).
Zoster virus with Combination
 The more recently licensed live,
attenuated Oka-strain VZV vaccine
(PROQUAD®) prepared in combination
with measles, mumps, and rubella vaccine
(MMRV) is formulated with a broad range
of titers that extend to over 60,000 PF
 Duration of Efficacy and of
Immunity
 Vaccine efficacy for zoster prevention
declined during the first year following
vaccination, but remained stable through
the remaining 3 years of follow up
Vaccine efficacy for PHN prevention had a
similar pattern, with an initial decline and
subsequent stabilization.
 Site of Injection is important
 Zoster vaccine should be administered as
a single 0.65-mL dose subcutaneously in
the deltoid region of the upper arm; a
booster dose is not licensed for the
vaccine. The vaccine should not be
injected intravascularly or intramuscularly
and should only be reconstituted and
injected using a sterile syringe free of
preservatives, antiseptics, and detergents,
which can inactivate the vaccine virus.
 Vaccines for Hepatitis A
 Hepatitis A vaccines licensed in the United
States are inactivated, whole-cell virus vaccines
that are produced from hepatitis A virus grown in
human diploid fibroblast cells. There are 2
single-antigen vaccines, Vaqta and Havrix, and
a combined hepatitis A/hepatitis B vaccine,
Twinrix (GlaxoSmithKline). The purified virus is
then formalin inactivated and adsorbed to
aluminum hydroxide. Havrix and Twinrix have 2-
phenoxyethanol added as a preservative,
whereas Vaqta is preservative free
 U S adopts to New vaccine
 All children who live in the United States
should receive hepatitis A vaccine at 1
year of age (ie, 12–23 months of age) as a
2-dose regimen. Immunization should be
integrated into the routine childhood
immunization schedule and completed
according to the approved schedules
using Havrix or Vaqta hepatitis A
vaccines. Administration of 2 doses of the
same hepatitis A
 Japanese B encephalitis
 Japanese B encephalitis
(JE), a mosquito-borne
Arboviral infection, is the
leading cause of viral
encephalitis in Asia
Approximately 50,000
sporadic and epidemic
cases of JE are reported
annually from the
People's Republic of
China (PRC), Korea,
Japan, Southeast Asia,
the Indian subcontinent,
and parts of Oceania.
Prevalence of Japanese B
Encepalitis
 INACTIVATED JAPANESE B
ENCEPHALITIS VIRUS VACCINE
 An inactivated JE vaccine derived from infected mouse
brain has been licensed in Japan since 1954 (24). JE
vaccine licensed in the United States is produced by the
Research Institute of Osaka University (Biken) and is
distributed by Connaught Laboratories Inc. The Biken
vaccine is the most widely used JE vaccine of its type.
 Similar mouse brain derived JE vaccines are produced
by other manufacturers in India, Japan, Korea, Taiwan,
Thailand, and Vietnam In the PRC, inactivated and
attenuated JE vaccines are produced in primary hamster
kidney cells
SWINE FLU VACCINE
 H1 N1 old infection and New
Threat
 H1N1 is a new virus
that was first
detected in people
in April 2009. It was
originally referred
as “swine flu”
because many of
the genes in this
new virus were
similar to influenza
viruses that occur in
pigs.
Successful and Safe Vaccine for
H1N1
 The National Institute of Allergy and Infectious
Diseases, part of the National Institutes of
Health, has conducted swine flu clinical trials to
make sure the new swine flu vaccines are safe
and effective. They were conducted at eight
university research hospitals and medical
organizations across the United States,
including Baylor College of Medicine in Houston,
Children's Hospital Medical Centre in Cincinnati,
and Emory University in Atlanta.
Who should get Vaccinated for
H1 N1
 CDC recommends influenza vaccination
as the first and most important step in
protecting against the flu. CDC is
encouraging anyone who wants to protect
themselves against 2009 H1N1 to get
vaccinated, including people 65 years and
older. While less likely to get sick with
2009 H1N1 than younger people, people
65 and older are at high risk of serious
complications if they do become ill.
 FDA approved H1 N1 vaccines
 The U.S. Food and Drug Administration an has
approved four vaccines against the 2009 H1N1
influenza virus
 The vaccines are made by CSL Limited,
MedImmune LLC, Novartis Vaccines and
Diagnostics Limited, and sanofi pasteur Inc. All
four firms manufacture the H1N1 vaccines using
the same processes, which have a long record
of producing safe seasonal influenza vaccine
 Influenza A (H1N1) 2009
Monovalent Vaccine
 INDICATIONS AND USAGE
 Influenza A (H1N1) 2009 Monovalent Vaccine
is an inactivated influenza virus vaccine
indicated for active immunization of persons 4
years of age and older against influenza
disease caused by pandemic (H1N1) 2009
virus .
 DOSAGE AND
ADMINISTRATION

 Based on currently available information the

vaccination regimen is as follows:
 Children 4 through 9 years of age: Two 0.5-mL
intramuscular injections approximately 1 month
apart Children 10 through 17 years of age: A
single 0.5-mL intramuscular injection
 Adults 18 years of age and older: A single 0.5-
mL intramuscular injection
 Hepatitis B vaccination included in
several Vaccination Programme
 Hepatitis B vaccines are effective and safe. Up
to 95% of vaccinated individuals form effective
antibodies when they get the vaccine and are
protected from hepatitis B. In healthcare
workers, high-risk public safety workers, dialysis
patients, and sexual partners of infected
persons, a blood test for antibodies is
recommended after vaccination to ensure that
the person produced antibodies. For the few
who do not form antibodies, revaccination may
improve response, especially in infants
 Licensed Vaccines That Are Not Being
Used
Widely
 New/Improved:
 • Hib: PRP-conjugates
 • Pneumococcus: PS-conjugates
 • Cholera: inactivated
 • Rotavirus: live, attenuated
 • Typhoid: Vi, Ty2la
 • Pertussis: Acellular
 • HAV: Inactivated
 • Group A Meningococcus: PS-conjugates
 • Rabies: Cell-culture based
 • Varicella: Live-attenuated
 Progress to prevent H Pylori
H. pylori is among commonest bacterial infections in humans, and
may be be transmitted by water and oral fecal spread.
Genomics may help understanding the pathogenesis of H. pylori
infection and development of new therapies, including H. pylori–
specific antimicrobial agents and vaccines
Enormous progress in studying the virulence factors of H. pylori
and their variation, but not yet used in clinical practice
Px and Rx vaccination have been successful in animal models, but the
translation to human vaccine remains difficult
These developments will be needed to prevent and treat this infection in areas of
the world where there is a high prevalence of chronic infection
 New Vaccine Strategies
Vaccine development
 Purified (Subunits) Antigens vaccine
e.g. Hepatitis B, Haemophilus influenza
type b, RSV, Rotavirus, foot-and-mouth
disease
 Conjugate vaccines e.g. meningitis,
pneumonia
 Recombinant antigen vaccines e.g.
Hepatitis B, malaria
Vaccine trails for HIV
prevention
HIV Vaccine Approaches
Protein subunit

Synthetic peptide

Naked DNA

Inactivated Virus

Live-attenuated
Virus
Live-vectored Vaccine
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 other systems: Success
against other viral infections
 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
 Status of HIV Vaccine
Development
 Over 60 Phase I/II trials of 30 candidate
vaccines
 United States, Thailand, South Africa,
Brazil
 One Phase III trial
 VaxGen gp120 protein subunit vaccine
 CDC collaborating the research
on Vaccine for HIV infection
 CDC played an important role in the trials (VAX003 and
VAX004) that evaluated the efficacy of gp120-based
vaccine candidates. VaxGen, which also sponsored the
trials. CDC sponsored a series of behavioural and
biomedical studies linked to the VAX004 efficacy trial in
North America and was part of the consortium that
conducted the VAX003 trial in Thailand. Although the
vaccine candidates failed to prevent HIV infection, the
successful conduct of these trials proved that large HIV
vaccine efficacy trials were possible, even in developing
countries.
Difference between a preventive
HIV vaccine and a therapeutic
HIV vaccine?
 Therapeutic HIV vaccines are designed to
control HIV infection in people who are
already HIV positive Preventive HIV
vaccines are designed to protect HIV
negative people from becoming infected
or getting sick. This fact sheet focuses on
preventive HIV vaccines.
Malaria Vaccines in
Progress
 Vaccine trails in Malaria
 More than a dozen
vaccine candidates
are now in clinical
development, and
one, GlaxoSmithKline
Biologicals’ RTS,S, is
in Phase III clinical
testing—the first
malaria vaccine
candidate to advance
third stage of testing
Phase III trial in Malaria
 Phase III trial of the
world’s most clinically
advanced malaria
vaccine candidate was
launched in Kisumu,
Kenya, in July 2009,
under the auspices of the
Kenya Medical Research
Institute (KEMRI)/CDC
Research and Public
Health Collaboration.
 Vaccine Candidate—
GlaxoSmithKline Biological
 The vaccine candidate—GlaxoSmithKline
Biological' (GSK Bio) RTS,S—is the first of the
current generation of malaria vaccines to
warrant Phase III testing on this scale. The
vaccine has a promising safety profile, was more
than 50% effective in reducing episodes of
clinical malaria in children 5 to 17 months old in
earlier testing, and can be administered together
with the package of vaccinations routinely given
to African children.
 Very young taken for trails in view of
High mortality and Morbidity
 Phase III trial will
demonstrate how the
vaccine performs in two
groups of children—one
aged 6 to 12 weeks and a
second aged 5 to 17
months—in different
transmission settings
across a wide geographic
region in Africa.
Malaria Vaccine possible in next
few years
 In Phase II testing,
the vaccine reduced
cases of malaria in
young children 5 to 17
months by 53%. If
Phase III results are
as good, the vaccine
could be fully
available in the next 5
- 10 years.
DNA Vaccines
 DNA Vaccines
 DNA vaccines are at
present experimental,
but hold promise for
future therapy since
they will evoke both
Humoral and Cell-
mediated immunity,
without the dangers
associated with live
virus vaccines.
What are DNA Vaccines?

From Scientific
American, July 1995
 Making DNA Vaccines
 The gene for an antigenic determinant of a
pathogenic organism is inserted into a plasmid.
This genetically engineered plasmid comprises
the DNA vaccine which is then injected into the
host. Within the host cells, the foreign gene can
be expressed (transcribed and translated) from
the plasmid DNA, and if sufficient amounts of the
foreign protein are produced, they will elicit an
immune response
Genetic Engineering a great tool
in developing newer vaccines
 It is possible, using genetic engineering, to introduce
a gene coding for an immunogenic protein from one
organism into the genome of another (such as
vaccinia virus). The organism expressing a foreign
gene is called a recombinant. Following injection into
the subject, the recombinant organism will replicate
and express sufficient amounts of the foreign protein
to induce a specific immune response to the protein.
 Genetically Engineered
Vaccines a future tool
 DNA vaccination is a technique for protecting
an organism against disease by injecting it with
genetically engineered DNA to produce an
immunological response. Nucleic acid vaccines
are still experimental, and have been applied to
a number of viral, bacterial and parasitic models
of disease, as well as to several tumour models.
DNA vaccines have a number of advantages
over conventional vaccines, including the ability
to induce a wider range of immune response
types.
 DNA Vaccines are 3 rd

Generation vaccines
 DNA vaccines are third generation
vaccines, and are made up of a small,
circular piece of bacterial DNA (called a
plasmid) that has been genetically
engineered to produce one or two specific
proteins (antigens) from a micro-organism.
The vaccine DNA is injected into the cells
of the body, where the "inner machinery"
of the host cells "reads" the DNA and
converts it into pathogenic proteins.
Advantages of DNA Vaccines
Over Other Types of Vaccines
 cheaper and easier to produce
 safer
 can elicit antibody and cellular immune
responses
 stable at a broad range of temperature (no
cold-chain requirement)
 can be designed and produced by genetic
engineering to have only the desired antigens
or antigenic sequences (epitopes) in the
vaccine
The New GMO Swine Flu
Corn Flakes
 Iowa State University
researchers are putting
flu vaccines into the
genetic makeup of corn,
which may someday
allow pigs and humans
to get a flu vaccination
simply by eating corn
or corn products.
 WHO Initiative for Vaccine
Research (IVR)
 The WHO Initiative for Vaccine Research
was established in 2001 to streamline the
various vaccine research and
development projects being carried out by
different departments of WHO (including
the Special Programme for Research and
Training in Tropical Diseases: TDR) and
UNAIDS.
 Importance Of Vaccines For
Adults
 Most effective strategies for preventing
illness
 Deaths from VPD still occur
 Viewed as routine for children and
travelers but not for adults
 Make immunizations integral part of
patient care
 Why we should support
vaccination
 We don't vaccinate just to protect our children.
We also vaccinate to protect our grandchildren
and their grandchildren. With one disease,
smallpox, we "stopped the leak" in the boat by
eradicating the disease. Our children don't have
to get smallpox shots any more because the
disease no longer exists. If we keep vaccinating
now, parents in the future may be able to trust
that diseases like polio and meningitis won't
infect, cripple, or kill children.
 Vaccine Controversies
 The public health benefits of vaccinations
are exaggerated. Critics of vaccination
policy point out that the mortality rates of
some illnesses were already dramatically
reduced before vaccines were introduced,
and claim that further reductions cannot
immediately be attributed to vaccines.
 Secondary and long-term effects on the
immune system from introducing
immunogens directly into the bloodstream
are not fully understood.
 Vaccine Controversies
 Vaccinations contain chemical
components that are known to be
toxic, such as formaldehyde,
aluminum in various compounds,
acetone, glyceride, ethylene glycol,
and neomycin when injected in large
enough quantities
 Can some vaccines cause
Cancers ?
 Some researchers
hypothesize possible
links between the
increasing incidence of
cancer and use of
vaccines, suggesting
links to the way
vaccines may alter the
cells in our bodies.
 Vaccine development
A Complex Research
 Vaccine development for emerging and re-
emerging diseases is a complex issue
 There are many mechanisms already in place to
help deal with the development of preventive
vaccines for emerging and re-emerging diseases
 Close communication between the Sponsor and
the Agency will hopefully aid in more efficient
product development
 Vaccines Can Contain Dangerous
Ingredients Not Adequately Reported to
the Public ?
Public do challenge the safety of
Several Vaccines
 Anti-vaccine lobbyists
 Not everybody believes that vaccines are good
 Despite the ridiculousness of anti-vaccine
arguments, there are significant and influential
followers
They can bring untold damage to immunization
programs and cause diseases and deaths

 • Recent examples
 – Northern Nigeria and polio
 – MMR and measles in UK
 – Hepatitis B in India
 All the New Vaccines are Under
Scanner by Health Authorities and
Social Activists
Luc Montagnier on Vaccine
for AIDS
 Our goal is not to
completely eradicate the
infection - that would be
very difficult - but to
produce a vaccine that
will prevent not infection
but disease. I think this is
more possible.

It's clear that prevention
will never be sufficient.
That's why we need a
vaccine that will be
safe.
Are we getting the Vaccines
in TIME
Created for Dr.T.V.Rao MD’s
‘e’ learning Programme
Email
doctortvrao@gmail.com