History
of vaccination
For centuries,
human beings have looked for ways to be protected from deadly diseases and thus
vaccination has a long history. Vaccines have saved more human lives than any
other medical invention in history.
·
From as early as 200 BCE and during the
15th century, people in different parts of the world have attempted to prevent
illness by intentionally exposing healthy people to smallpox and this practice
was termed as variolation. In 1721, Lady Mary Wortley Montagu brought smallpox
inoculation to Europe by inoculating her two daughters against smallpox as she
had observed this practice in Turkey.
·
In 1774, Benjamin Jesty hypothesised that
infection with cowpox could protect a person from smallpox. In May 1796, English physician Edward Jenner
e inoculated 8-year-old boy, James Phipps, with matter collected from a cowpox
sore on the hand of a milkmaid. Phipps suffered a local reaction and felt
unwell for several days. Two months
later, in July 1796, Jenner inoculated Phipps with matter from a human smallpox
sore and Phipps becomes the first human to be vaccinated against smallpox. The
term ‘vaccine’ was later coined by Louis Pasteur (From the Latin word for cow,
vacca).
·
In 1872, Louis Pasteur created the first
laboratory-produced vaccine - vaccine for fowl cholera in chickens. In 1885,
Louis Pasteur successfully prevented rabies through post-exposure vaccination.
Pasteur gave a course of 13 injections containing rabies virus to a rabid dog
bitten boy, Joseph Meister. Meister survived and later becomes the caretaker of
Pasteur’s tomb in Paris.
·
In 1894, Dr Anna Wessels Williams isolated
a strain of the diphtheria bacteria that was used for the development of diphtheria
antitoxin. In 1937 Max Theiler, Hugh
Smith and Eugen Haagen developed the 17D vaccine against yellow fever and
Theiler was awarded Nobel Prize.
·
In 1939, bacteriologists Pearl Kendrick
and Grace Eldering demonstrated the efficacy of the pertussis (whooping cough)
vaccine. By 1945 -1946 the first influenza vaccine was approved through the
research led by Thomas Francis Jr and Jonas Salk.
·
From 1952–1955, the first effective polio
vaccine was developed by Jonas Salk (Killed vaccine) and by 1960, a second type
of polio vaccine was developed by Albert Sabin (Live Vaccine, could be given
orally). Czechoslovakia was the first
country in the world to eliminate polio.
·
In 1967, the World Health Organization
announces the Intensified Smallpox Eradication Programme, to eradicate smallpox
through surveillance and vaccination.
·
In 1969, Dr Baruch Blumberg and Irving
Millman developed the first hepatitis B vaccine, by heat-treating the virus.
·
In 1971 the measles vaccine combined with vaccines
against mumps and rubella into a single vaccination (MMR) by Dr Maurice Hilleman.
·
In 1974 the Expanded Programme on
Immunization (EPI, now the Essential Programme on Immunization) was established
by WHO to develop immunization programmes throughout the world. The first
diseases targeted by the EPI are diphtheria, measles, polio, tetanus,
tuberculosis and whooping cough.
·
In 1980 the WHO declared smallpox as
eradicated.
·
In 1988, WHO launched Global Polio
Eradication Initiative.
·
In 1999 the first vaccine against
rotavirus was approved and a lower-risk version of the vaccine is introduced in
2006.
·
In 2006 the first vaccine for Human
Papillomavirus (HPV) is approved.
·
On 2020, WHO declared COVID-19 as a
pandemic. Effective COVID-19 vaccines were
developed, produced and distributed with unprecedented speed. In December 2020,
just 1 year after the first case of COVID-19 was detected, the first COVID-19
vaccine doses are administered.
As per WHO
Statistics, we now have vaccines to prevent more than 20 life-threatening
diseases and these vaccines help people of all ages to live a longer and
healthier life and prevents nearly 3.5 to 5 million deaths every year from
diseases such as diphtheria, pertussis, tetanus, influenza and measles.
The principle of
Vaccination is the exploitation of the extraordinary ability of our highly
evolved immune system to respond to and remember their encounters with
antigens.
A vaccine is a
biological product that can be used to safely induce an immune response that
confers protection against infection and/or disease on subsequent exposure to
the corresponding pathogen. Vaccine contain antigens that are either derived
from the pathogen or produced synthetically to represent components of the
pathogen. The essential components of vaccines are one or more protein or
polysaccharide antigens.
Types
of Vaccines
Vaccines are
generally classified as live or non-live (inactivated). Live vaccines contain attenuated replicating
strains of the relevant pathogenic organism and Nonlive or attenuated Vaccines
contain killed whole organisms only components of a pathogen. In addition to
these two classes, several new types have emerged recently such as those
prepared based on viral vectors, nucleic acid-based RNA and DNA vaccines,
virus-like particles, etc.
Live
vaccines
Live vaccines
contain live pathogens (either a bacteria or a virus) that have been
"attenuated," or weakened. In an immunocompetent host they replicate
sufficiently to produce a strong immune response, but not so much as to cause a
significant disease. Here the immune
system reacts very well to vaccination and a very long time immunity results.
Booster doses are not always needed.
Example are -
vaccines for measles, mumps, rubella and rotavirus, oral polio vaccine, the
Mycobacterium bovis bacillus Calmette–Guérin (BCG) vaccine for TB and live
attenuated influenza vaccine.
Non-live
vaccines
Non-live vaccines
are killed whole organisms (whole-cell pertussis vaccine and inactivated polio
vaccine) or purified proteins from the organism (acellular pertussis vaccine)
or recombinant proteins (hepatitis B virus vaccine) or polysaccharides
(pneumococcal vaccine against S.
pneumoniae). Toxoid vaccines are
formaldehyde-inactivated protein toxins purified from the pathogen (tetanus and
diphtheria).
Non-live vaccines are
often combined with an adjuvant to improve their immunogenicity or ability to
induce an immune response. Examples of
adjuvants are aluminium salts (alum) and oil-in-water emulsion
Subunit
vaccines
Subunit vaccines
are made from a piece of a pathogen. Some important subunit vaccines are
polysaccharide vaccines, conjugate vaccines, and protein-based vaccines.
Subunit vaccines can be made either from the original pathogen or by using
recombinant technique.
Polysaccharide
vaccines contain the capsular polysaccharides as the antigen and activate immune
response against the respective pathogenic bacteria. Pneumococcal
polysaccharide vaccine is an example.
A conjugate
vaccine is a type of subunit vaccine in which a weak antigen is combined with a
strong antigen as a carrier so that the immune system will produce a stronger
response to the weak antigen. Examples are pneumococcal and meningococcal
conjugate vaccines
Protein-based
vaccines contain a specific protein from the surface of a virus or bacteria. Example is the recombinant hepatitis B
vaccine and Novavax COVID-19 vaccine.
Since Subunit
vaccines contain only pieces or fragments from a pathogen, it does not cause
disease, but only activates the immune system and thus they are suitable for
children, older and immunocompromised individuals.
Recombinant
vaccines are immunogenic proteins developed with the help of recombinant DNA
technology. This involves inserting the DNA encoding the antigen into a host
bacterial or mammalian cells, where the antigen will be expressed. It could be isolated and purified and used as
vaccine. Examples: Vaccine against
Hepatitis B, Influenza B and Meningitis.
Toxoid
Vaccine
Toxoid is an inactivated toxin (usually an
exotoxin) whose toxicity has been suppressed either by chemical or heat
treatment, but the immunogenicity is maintained. Toxoid vaccines are effective
and safe vaccines against diseases such as tetanus and diphtheria.
Viral vaccines and Bacterial vaccines
Viral vaccines
contain either inactivated or attenuated viruses and bacterial vaccines contain
either inactivated or attenuated bacteria.
Examples of
viral vaccines are vaccines against Measles, Mumps, Rubella, Chickenpox, Polio,
Influenza, Hepatitis A, Hepatitis B, Rabies, Rotavirus, Human papillomavirus,
etc.
Examples of
bacterial vaccines are vaccines against Diphtheria, Tetanus, Whooping cough,
Meningitis, Pneumonia, Typhoid, Cholera, Plague, Anthrax, Tuberculosis,
Tularemia, Typhus, etc
Different
Types and Generations of Vaccines
Vaccines
are divided to 3 generations based on the process of evolution
First-Generation Vaccines
Attenuated
and inactivated vaccines are the first generation and known as traditional
vaccine. Attenuated pathogens, full organisms or inactivated bacterial toxin are
used in making these vaccines. Advantages are their high ability to stimulate
innate immunity, induction of long-term protection, easy production, and low
production costs. Disadvantages such as disease due to the use of complete
pathogen (live or inactivated) and virulence reversal of the pathogen in the
host.
Second-Generation Vaccines
Second-generation
vaccines are based on subunit elements, recombinant or synthetic proteins,
non-protein antigens, and expressed bacterial imunogene or viruses, which
include numerous molecules and epitopes of different species and strains of
pathogens. The subunit, conjugated, and recombinant vaccines are in this
generation.
Third-Generation Vaccines
Immunogenic
potential administration of a plasmid containing a gene encoding the antigen is
the as third generation vaccines. These
are known as genetic vaccines, DNA vaccines, RNA vaccines, and plasmid
vaccines. These use engineered DNA or
RNA to induce an immunologic response in the host against bacteria, parasites,
viruses, cancer, etc
|
1st generation |
|
|
Live attenuated vaccines |
MMR,
Influenza, OPV, Chickenpox, Yellow fever, Hepatitis A |
|
Inactivated vaccines |
Influenza,
Hepatitis B, IPV, Rabies, Cholera, Plaque, Pertussis |
|
2nd generation |
|
|
Subunit vaccines |
Hepatitis
B, Diphtheria, Pertussis, Anthrax, Hemophilus Influenza B |
|
Recombinant vaccines |
Hepatitis
B, HSV, Rota virus, HPV, FMD |
|
3rd generation |
|
|
DNA vaccines |
HIV,
Malaria, Cancer, Influenza, Ebola, Hepatitis, HPV |
Different routes of administration of vaccines
Route of
administration is the way by which a drug is taken into the body. They are generally classified by the location
in body where the drug is applied. Common routes of administration include
topical (local), oral (enteral, delivered through the gastrointestinal tract)
and parenteral (any route that is not enteral - intravenous (IV), intramuscular
(IM), subcutaneous (SC) and intradermal (ID)).
Oral Route (PO)
Oral vaccine is
administered through drops to the mouth. Rotavirus vaccine and Oral Polio Vaccine
are administered orally. These should never be injected. Oral vaccines activate immune cells in the
mucousal membranes lining the gastrointestinal tract which is beneficial in
protecting against diseases that affect the gut.
Intranasal Route (NAS)
Intranasal
vaccine is administered into nostril using a nasal sprayer. Live, attenuated
influenza Vaccine is administered by the intranasal route.
Subcutaneous Route (Subcut)
Subcutaneous
injections are administered into the fatty tissue found below the dermis and
above muscle tissue. Vaccines given
through subcutaneous administration are absorbed at a slower and constant rate
as there is less blood supply in subcutaneous tissue.
Intramuscular Route (IM)
Intramuscular
injections are administered into the muscle through the skin and subcutaneous
tissue. Since Muscle contains several
blood vessels, the vaccine disperse easily. In addition, muscles contain
dendritic cells that initiate a long-lasting immune response. Intramuscular
vaccines tend to have fewer side-effects other than redness and pain at the
injection site.
Intradermal (ID) Route (ID)
The injection
is administered just below the skin or the dermal layer of the skin. The epidermal and dermal layers of skin
contain many antigen-presenting cells that play a significant role in mediating
an efficient and protective immune response to vaccines.
Each vaccine
has a recommended administration route and site. Any deviation from the
recommended route may reduce vaccine efficacy or increase local adverse
reactions. Health care personnel should
always perform proper hand hygiene before administering vaccines.
Except bacille
Calmette-Guérin (BCG) vaccine and smallpox vaccine (these are administered by
the percutaneous route), all other injectable vaccines are administered by
the intramuscular or subcutaneous route.
Booster dose
A booster dose is extra administration of a vaccine after first or
primer dose. It provides re-exposure to the antigen and help to increase
immunity against that antigen back to protective levels if it has declined
through time. For example, tetanus shot boosters are often recommended every 10
years, since by that time the memory cells specific against tetanus lose their
function or undergo apoptosis.
Vaccine Components
·
Antigen - The
active component of the vaccine that causes an immune response.
·
Adjuvants - enhances
the effectiveness of vaccine. Most vaccines use aluminum-based adjuvants. They
induce a range of inflammatory factors to the injection site which helps the
immune response.
·
Preservatives -
stop unwanted contamination of a vaccine. The most common preservative is
2-phenoxyethanol. Thimerosal is a
mercury-containing preservative used in multi-dose vaccines to prevent
contamination of virulent bacteria or fungus.
·
Stabilizers - Stabilizers,
such as gelatin, stop chemical reactions in the vaccine and prevent the
components from separating. Other stabilizers include amino acids, potassium,
sodium, and lactose.
·
Buffers - Buffers
keep the vaccine at a similar pH to the body.
·
Adjusting
tonicity - To keep the vaccine isotonic to reduce local reactions, often Sodium
Chloride is added.
·
Surfactants and
emulsifiers - These agents act like a detergent. A commonly used surfactant is
called Polysorbate 80 or Tween®.
·
Formaldehyde - Formaldehyde
is used to detoxify or inactivate bacteria or toxin used in some vaccines.
·
Antibiotics - to
prevent bacterial growth during storage of the vaccine.
BCG
BCG or Bacille Calmette-Guerin is the only vaccine against
tuberculosis. It is named after its
inventors Albert Calmette and Camille Guérin.
Mycobacterium tuberculosis is
the ethiological agent of tuberculosis (TB).
TB is a leading cause of human disease and death, particularly in
developing countries. One dose of BCG is
recommended in healthy babies as soon as possible immediately after birth.
The vaccine is given intradermally and often redness, swelling, and mild
pain occur at the site of injection, a small ulcer may also form where some
scarring will be left after healing. BCG
vaccination can cause a false positive Mantoux test.
OPV and IPV
There is no cure for polio or poliomyelitis caused by Polio Virus, but
it can be prevented with safe and effective vaccination. Poliomyelitis is a
crippling disease that results from infection with any one of the three related
poliovirus types (referred to as types P1, P2, and P3), members of the
enterovirus (picornavirus) family. Poliovirus is transmitted from one person to
another by oral contact with secretions or faecal material from an infected
person.
Polio vaccine is to be given multiple times and it always protects a
child for life. There are six different vaccines against polio
- Inactivated polio vaccine (IPV) – protects
against poliovirus types 1, 2, and 3
- Trivalent oral polio vaccine (tOPV) – protects
against poliovirus types 1, 2, and 3
- Bivalent oral polio vaccine (bOPV) – protects
against poliovirus types 1, and 3
- Monovalent oral polio vaccines (mOPV1, mOPV2
and mOPV3) – protect against each individual type of poliovirus,
respectively
Inactivated polio vaccine (IPV) - An inactivated polio vaccine (IPV) was
developed by Dr. Jonas Salk in 1955. IPV
is produced from wild-type poliovirus strains of each serotype inactivated with
formalin. It can be administered alone
or in combination with other vaccines (e.g., diphtheria, tetanus, pertussis,
hepatitis B, and haemophilus influenza). Generally, three spaced doses are
administered and in most countries a booster dose is added during late
childhood. IPV has been used successfully in the polio eradication programs in
a few countries. IPV provides serum immunity to all three types of poliovirus.
Oral
polio vaccine (OPV) - A live attenuated oral polio vaccine (OPV) was developed
by Dr. Albert Sabin in 1961. OPV
consists of a mixture of live attenuated poliovirus strains of three serotypes.
Three or more spaced doses of OPV are required. The action of OPV is
two-pronged. OPV produces antibodies (humoral or serum immunity) against all
three types of poliovirus and this protects the individual against polio
paralysis by preventing the spread of poliovirus to the nervous system. OPV
strain also produce a local immune response in the 'mucous membrane lining in
the intestine (intestine is the primary site for poliovirus multiplication).
The antibodies produced there inhibit the multiplication of subsequent
infections with polio.
In
very rare cases, OPV results in vaccine-associated paralysis due to reversion
of the vaccine strains to wild poliovirus.
DPT
DPT vaccine
can prevent Diphtheria, Tetanus, and Pertussis (Whooping Cough). The vaccine components are diphtheria and
tetanus toxoids and either killed whole cells or antigen of the bacterium that
causes pertussis. If whole cells
included, then vaccine is termed as "DTwP" and if acellular antigen
is included, then termed as "DTaP".
DTP vaccine does not contain any live pathogen and therefore there is no
risk of use.
WHO recommends the first dose be administered as early as 6 weeks of age
and subsequent doses to be given 4-8 weeks apart, at age of 10-14 weeks and
14-18 weeks. A booster dose is to be given during the second year of life.
MMR
MMR vaccine was developed by Maurice Hilleman. MMR vaccine can prevent measles, mumps, and
rubella. MMR vaccine is administered by
a subcutaneous injection. The first dose
is generally given to children around 9 months to 15 months of age, with a
second dose at 15 months to 6 years of age,
TAB
TAB vaccine is
used against typhoid, TAB stands for Typhoid-paratyphoid A and B. There are two vaccines. One is an
un-conjugated polysaccharide vaccine given as a single dose and remain
effective for 3 years. Other is conjugated polysaccharide typhoid vaccine which
also is given as a single dose. The former can be administered after 2 years of
age while the conjugate vaccine can be given from 6 months onwards.
Mission
Indradhanush
Mission
Indradhanush (MI) was launched by the Ministry of Health and Family Welfare
(MoHFW), Govt of India on 25th December 2014. It is a special campaign under the Universal
Immunization Program (UIP), conducted to vaccinate all the children and
pregnant women left out or dropped out from Routine Immunization. Vaccination
is being provided against eight
vaccine-preventable diseases nationally, i.e. Diphtheria, Whooping Cough,
Tetanus, Polio, Measles, severe form of Childhood Tuberculosis and Hepatitis B
and meningitis & pneumonia caused by Haemophilus influenza type B and Rotavirus
Diarrhea and Japanese Encephalitis.
Contraindications
and Precautions to Vaccination
Contraindications
and precautions to vaccination are situations when vaccines should not be
administered.
A contraindication
is a health condition in the recipient that increases the likelihood of a
serious adverse reaction to a vaccine and vaccines should not be administered
when a contraindication is present.
Medical conditions
that are contraindications to vaccination include:
· A severe allergic reaction (e.g.,
anaphylaxis) to a vaccine component
· Severe immunosuppression is a
contraindication to live, attenuated vaccines.
· A history of intussusception is a
contraindication to rotavirus vaccination.
· Encephalopathy occurring within 7 days of
pertussis vaccination is a contraindication to subsequent doses of
pertussis-containing vaccine.
A precaution is a
health condition in the recipient that might increase the chance or severity of
a serious adverse reaction or might compromise the ability of vaccine to
produce immunity. Problem could result, but the chance of happening is less
than with a contraindication. Vaccines should be delayed when a a precaution is
present.
Medical conditions
that are precautions to vaccination include:
· Moderate or severe acute illness, with or
without fever.
· History of thrombocytopenia is a
precaution for MMR vaccine.
· Chronic gastrointestinal disease is
precaution for rotavirus vaccine.
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