Vaccines
Artificially Acquired Active Immunity
Mike Clark, M.D.
• Vaccines (organism dead or attenuated)
– Spare us the symptoms of the primary response
– Provide antigenic determinants that are immunogenic
and reactive
– Older vaccines target only one type of helper T cell
(TH 2 rather than TH 1) , so fail to fully establish
cellular immunological memory
– TH2 activates the B-cell system whereas TH 1 activates
the T-cell system
– Naked DNA vaccines and oral vaccines avoid this
problem
– Sometimes can become to something in vaccine – like
egg albumin found in the influenza vaccines
(adjuvants)
Vaccines
• 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 or its toxins. The agent stimulates
the body's immune system to recognize the agent
as foreign, destroy it, and "recognize" it, so that
the immune system can more easily recognize
and destroy any of these microorganisms that it
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).
• The term vaccine derives from Edward Jenner‘s
1796 use of the term cow pox (Latin variolæ
vaccinæ, adapted from the Latin vaccīn-us, from
vacca cow), which, when administered to humans,
provided them protection against smallpox.
History
• Sometime during the 1770s Edward Jenner heard
a milkmaid boast that she would never have the
often-fatal or disfiguring disease smallpox,
because she had 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, and six
weeks later variolated the boy's arm with
smallpox, afterwards observing that the boy did
not catch smallpox. Further experimentation
demonstrated the efficacy of the procedure on an
infant.
• Louis Pasteur generalized Jenner's idea by
developing what he called a rabies vaccine
(now termed an antitoxin), and in the 19th
century vaccines were considered a matter of
national prestige, and compulsory vaccination
laws were passed
• The 20th century saw the introduction of
several successful vaccines, including those
against diphtheria, measles, mumps, and
rubella. Major achievements included the
development of the polio vaccine in the 1950s
and the eradication of smallpox during the
1960s and 1970s.
• Problem: As vaccines became more common,
many people began taking them for granted.
• However, vaccines still remain elusive for many
important diseases, including malaria and HIV
Types of Vaccines (Dead Organism)
Some vaccines contain killed, but previously
virulent, micro-organisms that have been
destroyed with chemicals or heat.
Examples are the influenza vaccine, cholera
vaccine, bubonic plague vaccine, polio
vaccine, hepatitis A vaccine, and rabies
vaccine.
Types of Vaccines (Attenuated)
• Some vaccines contain live, attenuated microorganisms.
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, however some are
bacterial in nature.
• They typically provoke more durable immunological
responses and are the preferred type for healthy adults.
• Examples include the viral diseases yellow fever, measles,
rubella, and mumps and the bacterial disease typhoid.
• The live Mycobacterium tuberculosis vaccine is not made of a
contagious strain, but contains a virulently modified strain
called "BCG" used to elicit immunogenicity to the vaccine.
(Bacillus Calmette-Guérin – named after developers).
Vaccines (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. Not all toxoids are for micro-
organisms; for example, Crotalus atrox toxoid
is used to vaccinate dogs against rattlesnake
bites.
Vaccines ( Protein- Subunit) Epitope
• 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 extracted
from the blood serum of chronically infected
patients, but now produced by recombination of
the viral genes into yeast), the virus-like particle
(VLP) vaccine against human papillomavirus (HPV)
that is composed of the viral major capsid protein,
and the hemagglutinin and neuraminidase subunits
of the influenza virus.
Vaccines (Conjugate)
“making a complete antigen out of a partial one”
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.
Newly Developed Vaccines
• Recombinant Vector – by combining the physiology of one
micro-organism and the DNA of the other, immunity can be
created against diseases that have complex infection
processes
• Naked DNA vaccination – in recent years a new type of
vaccine called DNA vaccination, created from an infectious
agent's DNA, has been developed. It works by insertion
(and expression, triggering immune system recognition) of
viral or bacterial DNA into human or animal cells. Some
cells of the immune system that recognize the proteins
expressed will mount an attack against these proteins and
cells expressing them. Because these cells live for a very
long time, if the pathogen that normally expresses these
proteins is encountered at a later time, they will be
attacked instantly by the immune system. One advantage of
DNA vaccines is that they are very easy to produce and
store. As of 2006, DNA vaccination is still experimental.
Adjuvants
• An adjuvant is an agent that may stimulate the immune system and
increase the response to a vaccine, without having any specific
antigenic effect in itself. The word “adjuvant” comes from the Latin
word adjuvare, meaning to help or aid. "An immunologic adjuvant
is defined as any substance that acts to accelerate, prolong, or
enhance antigen-specific immune responses when used in
combination with specific vaccine antigens
• There are many known adjuvants in widespread use, including oils,
aluminium salts, and virosomes, although precisely how they work
is still not entirely understood.
Aluminium salts
• There are many adjuvants, some of which are inorganic (such as
alum), that also carry the potential to augment immunogenicity.
Two common salts include aluminium phosphate and aluminium
hydroxide. These are the most common adjuvants in human
vaccines
Booster Shots
• Unfortunately, one shot is not enough to protect a person from the disease you
are vaccinating against. Whenever a person is vaccinated the person's immune
system will activate a certain number of cells called B-cells. These B-cells will
multiply and some of them will produce antibodies. Others of these multiplying
B-cells will become memory cells. Memory B-cells can last for decades in our
bodies and are able to make antibody whenever the microorganism you are
vaccinated against infects your body. This first vaccine doesn't get enough of
these B-cells activated. Booster shots activate more B-cells. When more B-cells
are activated more antibodies are made. More antibody results in better
protection from the microorganisms you are vaccinated against. In other words
you get a higher (stronger) immune response
• The timing of a booster shot is also important. If you give it too soon then the
antibodies present in the blood from the first shot will eliminate the material in
the vaccine before you can activate more of those B-cells. Therefore, a waiting
period between shots is required to allow time for
Naked DNA Vaccines
• Oftentimes injected with a gene gun – allows stimulation of
both TH1 and TH2 lymphocytes
• A gene gun or a biolistic particle delivery system, originally
designed for plant transformation, is a device for injecting
cells with genetic information
Edible Vaccines
Oral vaccines produced in transgenic plants
• Hepatitis B virus (HBV) infection is probably the single most important
cause of persistent viremia in humans. The disease is characterized by
acute and chronic hepatitis, which can also initiate hepatocellular
carcinoma. The prevalence of this disease in developing countries
justified initial efforts to express HBV candidate vaccines in plants.
• Currently, two forms of HBV vaccines are available, both of which are
injectable and expensive: one purified from the serum of infected
individuals and the other a recombinant antigen expressed and
purified from yeast. We have transformed plants with the gene
encoding the hepatitis B surface antigen (HBsAg); this is the same
antigen used in the commercial yeast-derived vaccine. An antigenic
spherical particle was recovered from these plants which is analogous
to the recombinant hepatitis surface antigen (rHBsAg) derived from
yeast. Parenteral immunization of mice with the plant-derived material
has demonstrated that it retains both B- and T-cell epitopes, as
compared to the commercial vaccine.
To build these edible vaccines, researchers
take cells from plants and coax them to
multiply like bacteria cultures. Then they
insert the desired gene, and "plant" the cells
in a growing medium, where they sprout new
plants—and hopefully the antigen gene is
expressed in the fruit or vegetable.
ADVANTAGES
1.Edible means of administration
and gives excellent safety compared
to injection.
2.It generates systemic and mucosal
immunity. This is essential to avoid
respiratory and digestive tracts
infection.
3.Heat stability. Stable at room
temperature. No need of
refrigeration.
4.Mass production is possible.
5.Reduction in production costs.
6.Plants can be easily reproduced as
compared to animals, used as a
system for vaccines production.
7. Stimulates both T cell and B cell
activity
Hepatitis B Vaccine
• Vaccinate persons with any of the following indications and any
person seeking protection from hepatitis B virus (HBV) infection.
• Behavioral: Sexually active persons who are not in a long-term,
mutually monogamous relationship (e.g., persons with more than
one sex partner during the previous 6 months); persons seeking
evaluation or treatment for a sexually transmitted disease (STD);
current or recent injection-drug users; and men who have sex with
men.
• Occupational: Health-care personnel and public-safety workers
who are exposed to blood or other potentially infectious body
fluids.
• Medical: Persons with end-stage renal disease, including patients
receiving hemodialysis; persons with HIV infection; and persons with
chronic liver disease.
• Other: Household contacts and sex partners of persons with chronic
HBV infection; clients and staff members of institutions for persons
with developmental disabilities; and international travelers to
countries with high or intermediate prevalence of chronic HBV
infection
Dosing of Hepatis B Vaccine
• Administer or complete a 3-dose series of hepatitis B
vaccine to those persons not previously vaccinated.
The second dose should be administered 1 month after
the first dose; the third dose should be administered at
least 2 months after the second dose (and at least 4
months after the first dose). If the combined hepatitis
A and hepatitis B vaccine (Twinrix) is used, administer 3
doses at 0, 1, and 6 months; alternatively, a 4-dose
schedule, administered on days 0, 7, and 21–30
followed by a booster dose at month 12 may be used.
• Adult patients receiving hemodialysis or with other
immunocompromising conditions should receive 1
dose of 40 μg/mL
Duration of Protection for Hepatitis B
Vaccine
• Although initially it was thought that the hepatitis B vaccine did
not provide indefinite protection, this is no longer considered the
case. Previous reports had suggested vaccination would provide
effective cover of between five and seven years, but
subsequently it has been appreciated that long-term immunity
derives from immunological memory which outlasts the loss of
antibody levels and hence subsequent testing and administration
of booster doses is not required in successfully vaccinated
immunocompetent individuals. Hence with the passage of time
and longer experience, protection has been shown for at least 25
years in those who showed an adequate initial response to the
primary course of vaccinations, and UK guidelines now suggest
that for initial responders who require ongoing protection, such
as for healthcare workers, only a single booster is advocated at 5
years.