VACCINE

INDEX
 Introduction
 First Vaccine
 Effects
 Types of vaccine
 Other contents
 Vaccine effectiveness
 Production
 Vaccine hesitancy
 Adverse effects

Introduction

A vaccine is a biological preparation that provides active

acquired immunity to a particular infectious 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, its
toxins, or one of its surface
proteins. The agent stimulates the body's immune system to
recognize the agent as a threat, destroy it, and to further
recognize and destroy any of the microorganisms associated
with that agent that it may encounter in the future.

First vaccine

The first vaccine was introduced by British physician Edward

Jenner, who in 1796 used the cowpox virus (vaccinia) to
confer protection against smallpox, a related virus, in humans.

Jenner’s contribution was to use a substance similar to, but

safer than, smallpox to confer immunity. He thus exploited
the relatively rare situation in which immunity to one virus
confers protection against another viral disease.

The terms vaccine and vaccination are derived from Variolae

vaccinae (smallpox of the cow), the term devised by Edward
Jenner (who both developed the concept of vaccines and
created the first vaccine) to denote cowpox.
 Edward Jenner using smallpox vaccination

The science of vaccine development and production is termed

vaccinology.

Effects

There is overwhelming scientific consensus that vaccines are

a very safe and effective way to fight and eradicate infectious
diseases. The immune system recognizes vaccine agents as
foreign, destroys them, and "remembers" them.
When the virulent version of an agent is encountered, the
body recognizes the protein coat on the virus, and thus is
prepared to respond, by first neutralizing the target agent
before it can enter cells, and secondly by recognizing and
destroying infected cells before that agent can multiply to vast
numbers.

Limitations to their effectiveness, nevertheless, exist.

Sometimes, protection fails for vaccine-related reasons such
as failures in vaccine attenuation, vaccination regimens or
administration

Types of vaccine

Vaccines typically contain attenuated, inactivated or dead

organisms or purified
products derived from
them. There are several
types of vaccines in use.
These represent different
strategies used to try to
reduce the risk of illness
while retaining the ability to induce a beneficial immune
response.
Attenuated
 Some vaccines contain live, attenuated microorganisms.
Many of these are active viruses that have been
cultivated under conditions that disable their virulent
properties, or that use closely related but less dangerous
organisms to produce a broad immune response.
Although most attenuated vaccines are viral, some are
bacterial in nature.
 Examples include the viral diseases yellow fever,
measles, mumps, and rubella, and the bacterial disease
typhoid.

Inactivated
 Some vaccines contain inactivated, but previously
virulent, micro-organisms that have been destroyed
with chemicals, heat, or radiation – "ghosts", with
intact but empty bacterial cell envelopes. They are
considered an intermediate phase between the
inactivated and attenuated vaccines.
 Examples include IPV (polio vaccine), hepatitis A
vaccine, rabies vaccine and most influenza 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.
  Not all toxoids are for micro-organisms; for example,
Crotalus atrox toxoid is used to vaccinate dogs against
rattlesnake bites.

Subunit
 Rather than introducing an inactivated or attenuated
micro-organism to an immune system (which would
constitute a "whole-agent" vaccine), a subunit vaccine
uses a fragment of it to create an immune response. One
example is the subunit vaccine against hepatitis B, which
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).

 Another example is edible algae vaccines, such as the

virus-like particle (VLP) vaccine against human
papillomavirus (HPV), which is composed of the viral
major capsid protein.[60] Another example is the
hemagglutinin and neuraminidase subunits of the
influenza virus. A subunit vaccine is being used for
plague immunization.

Conjugate
 Certain bacteria have a polysaccharide outer coat that is
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.

Outer membrane vesicle

 Outer membrane vesicles (OMVs) are naturally
immunogenic and can be manipulated to produce potent
vaccines. The best known OMV vaccines are those
developed for serotype B meningococcal disease.

Heterotypic
 Heterologous vaccines also known as "Jennerian
vaccines", are vaccines that are pathogens of other
animals that either do not cause disease or cause mild
disease in the organism being treated.

 The classic example is Jenner's use of cowpox to protect

against smallpox. A current example is the use of BCG
vaccine made from Mycobacterium bovis to protect
against tuberculosis.

Genetic vaccine
The subgroup of genetic vaccines encompass viral vector
vaccines, RNA vaccines and DNA vaccines.
Viral vector
Viral vector vaccines use a safe virus to insert pathogen genes
in the body to produce specific antigens, such as surface
proteins, to stimulate an immune response.

RNA
An mRNA vaccine (or RNA vaccine) is a novel type of
vaccine which is composed of the nucleic acid RNA,
packaged within a vector such as lipid nanoparticles. Among
the COVID-19 vaccines are a number of RNA vaccines under
development to combat the COVID-19 pandemic and some
have been approved or have received emergency use
authorization in some countries.

DNA
DNA vaccination – The proposed mechanism is the insertion
and expression of viral or bacterial DNA in human or animal
cells (enhanced by the use of electroporation), triggering
immune system recognition. 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 potential advantage of DNA vaccines is that they are very
easy to produce and store.
 Other contents

A vaccine dose contains many ingredients, very little of which

is the active ingredient, the
immunogen. A single dose may
have merely nanograms of virus
particles, or micrograms of
bacterial polysaccharides. A
vaccine injection, oral drops or
nasal spray is mostly water. Other ingredients are added to
boost the immune response, to ensure safety or help with
storage, and a tiny amount of material is left-over from the
manufacturing process. Very rarely, these materials can cause
an allergic reaction in people who are very sensitive to them.

Adjuvants
 Vaccines typically contain one or more adjuvants, used
to boost the immune response. Tetanus toxoid, for
instance, is usually adsorbed onto alum. This presents the
antigen in such a way as to produce a greater action than
the simple aqueous tetanus toxoid. People who have an
adverse reaction to adsorbed tetanus toxoid may be given
the simple vaccine when the time comes for a booster.
Preservatives
 Vaccines may also contain preservatives to prevent
contamination with bacteria or fungi. Until recent years,
the preservative thiomersal (a.k.a. Thimerosal in the US
and Japan) was used in many vaccines that did not
contain live viruses.
 Many vaccines need preservatives to prevent serious
adverse effects such as Staphylococcus infection, which
in one 1928 incident killed 12 of 21 children inoculated
with a diphtheria vaccine that lacked a preservative.
Several preservatives are available, including thiomersal,
phenoxyethanol, and formaldehyde. Thiomersal is more
effective against bacteria, has a better shelf-life, and
improves vaccine stability, potency, and safety.

Excipients
Beside the active vaccine itself, the following excipients and
residual manufacturing compounds are present or may be
present in vaccine preparations
 Aluminium salts or gels are added to promote an earlier,
more potent response, and more persistent immune
response to the vaccine; they allow for a lower vaccine
dosage.
 Antibiotics are added to some vaccines to prevent the
growth of bacteria during production and storage of the
vaccine.
 Egg protein is present in the influenza vaccine and
yellow fever vaccine as they are prepared using chicken
eggs.
  Formaldehyde is used to inactivate bacterial products for
toxoid vaccines. Formaldehyde is also used to inactivate
unwanted viruses and kill bacteria that might
contaminate the vaccine during production.
 Monosodium glutamate (MSG) and 2-phenoxyethanol
are used as stabilizers in a few vaccines to help the
vaccine remain unchanged when the vaccine is exposed
to heat, light, acidity, or humidity.
 Thiomersal is a mercury-containing antimicrobial that is
added to vials of vaccines that contain more than one
dose to prevent contamination and growth of potentially
harmful bacteria. Due to the controversy surrounding
thiomersal, it has been removed from most vaccines
except multi-use influenza, where it was reduced to
levels so that a single dose contained less than a
microgram of mercury, a level similar to eating ten
grams of canned tuna.

Vaccine effectiveness

Vaccine efficacy or vaccine effectiveness is the percentage

reduction of disease cases in a vaccinated group of people
compared to an unvaccinated group.

For example, a vaccine efficacy or effectiveness of 80%

indicates an 80% decrease in the number of disease cases
among a group of vaccinated people compared to a group in
which nobody was vaccinated.

Vaccine efficacy studies are used to measure several

important and critical outcomes of interest such as disease
attack rates, hospitalizations due to the disease, deaths due to
the disease, asymptomatic infection, serious adverse events
due to vaccination, vaccine reactogenicity, and cost
effectiveness of the vaccine.

The efficacy or performance of the vaccine is dependent on

several factors:

 the disease itself (for some diseases vaccination performs

better than for others)
 the strain of vaccine (some vaccines are specific to, or at
least most effective against, particular strains of the
disease)
 whether the vaccination schedule has been properly
observed.
 idiosyncratic response to vaccination; some individuals
are "non-responders" to certain vaccines, meaning that
they do not generate antibodies even after being
vaccinated correctly.
 assorted factors such as ethnicity, age, or genetic
predisposition.
 Production

Vaccine production is fundamentally different from other

kinds of manufacturing –
including regular
pharmaceutical
manufacturing – in those
vaccines are intended to be
administered to millions of
people of whom the vast majority are perfectly healthy. This
fact drives an extraordinarily rigorous production process with
strict compliance requirements that go far beyond what is
required of other products.

Vaccine production has several stages. First, the antigen itself

is generated. Viruses are grown either on primary cells such
as chicken eggs (e.g., for influenza) or on continuous cell
lines such as cultured human cells (e.g., for hepatitis A).

Bacteria are grown in bioreactors (e.g., Haemophilus

influenzae type b). Likewise, a recombinant protein derived
from the viruses or bacteria can be generated in yeast,
bacteria, or cell cultures.

After the antigen is generated, it is isolated from the cells used

to generate it. A virus may need to be inactivated, possibly
with no further purification required. Recombinant proteins
need many operations involving ultrafiltration and column
chromatography. Finally, the vaccine is formulated by adding
adjuvant, stabilizers, and preservatives as needed.

The final stage in vaccine manufacture before distribution is

fill and finish, which is the process of filling vials with
vaccines and packaging them for distribution. Although this is
a conceptually simple part of the vaccine manufacture
process, it is often a bottleneck in the process of distributing
and administering vaccines.

Vaccine hesitancy

Vaccine hesitancy is a delay in acceptance, or refusal of

vaccines despite the availability of vaccine services. The term
covers outright refusals to vaccinate, delaying vaccines,
accepting vaccines but remaining uncertain about their use, or
using certain vaccines but not others.

There is an overwhelming scientific consensus that vaccines

are generally safe and effective.

Vaccine hesitancy often results in disease outbreaks and

deaths from vaccine-preventable diseases. Therefore, the
World Health Organization characterizes vaccine hesitancy as
one of the top ten global health threats.

Adverse effects

Vaccinations given to children, adolescents, or adults are

generally safe. Adverse effects, if any, are generally mild. The
rate of side effects depends on the vaccine in question.

Some common side effects include fever, pain around the

injection site, and muscle aches. Additionally, some
individuals may be allergic to ingredients in the vaccine.
MMR vaccine is rarely associated with febrile seizures.

Host-("vaccinee")-related determinants that render a person

susceptible to infection, such as genetics, health status
(underlying disease, nutrition, pregnancy, sensitivities or
allergies), immune competence, age, and economic impact or
cultural environment can be primary or secondary factors
affecting the severity of infection and response to a vaccine.

Elderly, allergen-hypersensitive, and obese people have

susceptibility to compromised immunogenicity, which
prevents or inhibits vaccine effectiveness, possibly requiring
separate vaccine technologies for these specific populations
or repetitive booster vaccinations to limit virus transmission.

Severe side effects are extremely rare. Varicella vaccine is

rarely associated with complications in immunodeficient
individuals, and rotavirus vaccines are moderately associated
with intussusception.

Bibliography

https://en.wikipedia.org/wiki
https://www.britannica.com
https://www.who.int