Vaccines- Definition, Principle, Types, Examples

A vaccine is a medical preparation given to provide immunity from a

disease. Vaccines use a variety of different substances ranging from dead microorganisms to
genetically engineered antigens to defend the body against potentially harmful
microorganisms.
Effective vaccines change the immune system by promoting the development
of antibodies that can quickly and effectively attack disease-causing microorganisms when it
enters the body, preventing disease development.
A vaccine may contain live-attenuated or killed microorganisms or parts or products
from them capable of stimulating a specific immune response comprised of protective
antibodies and T cell immunity.
A vaccine should stimulate a sufficient number of memory T and B lymphocytes to
yield effector T cells and antibody-producing B cells from memory cells.
The viral vaccines should also be able to stimulate high titers of neutralizing
antibodies. Injection of a vaccine into a nonimmune subject induces active immunity against
the modified pathogens.
Vaccination is immunization against infectious disease through the administration of
vaccines for the production of active (protective) immunity in humans or other animals.

Definition and History of Vaccines

 A vaccine is an agent that is prepared from an antigen or pathogen by either deactivating its
mechanisms of protein synthesis or denaturing or killing them. This allows the preparation
of an agent that can be introduced into the host in order to induce an immune reaction with
an ultimate protection end-game.
 The history of vaccines trails down to 1877 when Loise Pasteur developed a vaccine using
a weakened strain of the anthrax bacillus, Bacillus anthracis. He adapted a methodology of
attenuating the culture of anthrax bacillus by incubation at a high temperature of 42–43°C
and inoculated the attenuated bacilli in the animals, demonstrating that animals receiving
inoculation of such attenuated strains developed specific protection against anthrax.
 This concept was successfully demonstrated on a farm at Pouilly-le-Fort in 1881 by
vaccinating sheep, goats, and cows with the attenuated anthrax bacillus strain. The result
indicated that all the vaccinated animals survived an anthrax attack which the non-
vaccinated could not, hence they died of anthrax.
 Louis Pasteur also developed the first vaccine against rabies in humans in 1885, and it
saved millions around the globe.
 Pasteur coined the term vaccine in commemoration of Edward Jenner who used such
preparations for protection against smallpox. This led to the establishment of various
institutions in several countries in the world that prepared vaccines and studied infectious
diseases such as the Pasteur Institute in Paris.
How do vaccines work in Immune System?
 Vaccines are biological preparations that are made up of killed or attenuated
pathogens (virus or bacteria) or part of the surface of the antigen.
 The preparation is made in such a way that it can not cause disease on its own, but it
helps the body to develop a memory type of immunity. This means that if an
individual encounter or is infected by the same pathogen (whose part has been used to
prepare the vaccine), the immunity will ‘remember’ and induce a more vigorous
immune response against the pathogen.
 Initially, the innate immune response (primary response) elicited on the first
encounter with a pathogen, is normally slow and that is why one will display
symptoms of the disease before the immune system can elicit a reaction to kill the
pathogen, and therefore the body develops an adaptive immune response (secondary
response) through specialized immune cells which counter the pathogen and create a
long-lasting memory.
 Therefore, vaccination or the introduction of a vaccine into the body will have a
similar kind of immune reaction (secondary response) only that it will by-pass the
slow initial response but enables the body to acquire immunity (from the vaccine). In
other words, the vaccine tricks the body to believe that it has the disease, and
therefore, able to fight the disease. This makes the body be able to kill the pathogen
before it can have the chance to cause disease due to memory that is created from
vaccination.
 Vaccination is the safest and most common way to gain immunity against bacteria or
viruses that your body has yet to encounter.
 Generally, a vaccine works as follows:
 Administration of vaccine which contains antigens for a specific disease or pathogen
 Identification and recognition of the antigen in the vaccine as foreign, by the immune
system
  Development of antibodies by the immune system to neutralize the antigens.
 Storage of these immune effector antibodies as memory antibodies for future response
in case an individual is exposed to the live pathogen or disease.
 Significantly, vaccination is done to prevent diseases and wipe them out in
eventuality. Administration of a vaccine to a significant proportion of a population.
 Vaccines are given to prevent and eventually wipe out diseases. When a vaccine is
given to a significant portion of the population, it protects those who receive the
vaccine as well as those who cannot receive the vaccine. This concept is called “herd
immunity.” When a high percentage of the population is vaccinated and immune to a
disease, they do not get sick — so there is no one to spread the disease to others. This
herd immunity protects the unvaccinated population from contagious (spread from
person to person) diseases for which there is a vaccine.
Types of Vaccines and Their Characteristics
 Vaccines have proved to have a strong defense against some of the most fatal diseases and
if they were still unavailable, the survival of individuals would be based on their immune
defenses which could either resolve the infection or lead to death from the infection.
 Therefore, the use of vaccines means, the vaccine will mimic the pathogen and cause an
immune response that is similar to that that can be activated by the pathogen.
 Historically, these vaccines have eliminated fatal infections such as smallpox, almost
eliminated polio, and saved many individuals from typhus, tetanus, hepatitis A and B,
measles, rotavirus diseases, etc.
 However, still successful vaccines are yet to be developed for many deadly diseases that
cause chronic infections such as AIDS, hepatitis C, tuberculosis, malaria, and herpes
 Successful vaccines against these chronic diseases must be able to stimulate immune
responses that are similar to those resulting from most natural exposures to the pathogen
but still remains a challenge.
 Various vaccines have been designed and here is a detailed approach to how these vaccines
have been developed, those in use, and those still under experimentation.
 Major advances in understanding the complexities of the interaction of pathogens or
microbes with the human host have revolutionized vaccine developments and advances in
recent times. Coupled with advances in laboratory techniques and technologies, have aided
the development of new vaccine types.
 Some more developed approaches such as vaccinomics, which is the application of
genomics and bioinformatics to vaccine development, is a new approach that may solve the
problem of developing vaccines against microbes and parasites.
Vaccine types can broadly be classified into three groups:

1. Whole-organism Vaccines
Inactivated (Killed) Vaccine
Live-attenuated vaccines
Chimeric vaccine
2. Subunit Vaccines
Polysaccharide Vaccine
Conjugated Vaccines
Toxoid Vaccines
Recombinant Protein Vaccines
Nanoparticle vaccines
3. Nucleic Acid Vaccines
DNA plasmid vaccines
mRNA vaccines
Recombinant vector vaccine
Whole-organism Vaccines
Many vaccines that were developed early consist of an entire pathogen that is either killed
(inactivated) or weakened (attenuated) so that they cannot cause disease. They are known as
the whole-organism vaccines. These vaccines elicit strong protective immune responses and
many vaccines used today are prepared in this manner, but not all disease-causing microbes
can be effectively targeted with a whole-organism vaccine.
1. Inactivated (Killed) Vaccine
 These were produced by killing the pathogen (bacteria, virus, or other pathogens) with
chemicals or heat, or radiation.
 The killed pathogen can not cause disease, and this means that they do not replicate in the
host’s body.
 Advantage: These vaccines are stable and safer than the live attenuated vaccines
 Disadvantage: The major disadvantage of this type of vaccine is that it elicits a weaker
immune response and therefore, it requires more vaccine dosages and a booster dose as
well, so as to confer protective immunity.
 Examples of Inactivated Vaccines include poliomyelitis (sulk vaccine), rabies, typhoid,
cholera, pertussis, pneumococcal, rabies, hepatitis B, and influenza vaccines.
2. Live-attenuated vaccines
 These vaccines were developed in the 1950s when advances in tissue culture techniques
were developed.
 These vaccines are prepared from a whole organism, by weakening their pathogenicity so
that they can not cause disease but can induce an immune response, hence the
term attenuation.
 These vaccines elicit strong immune responses because they are similar to the actual
disease pathogen and hence they confer a life-long immunity after only one or two doses,
therefore they are very effective.
 They are also relatively easy to create for certain viruses, but difficult to produce for more
complex pathogens like bacteria and parasites.
 Disadvantages: There is a remote chance that the weakened germ can mutate or revert
back to its full strength and cause disease.
 Live attenuated vaccines should not be given to individuals with weakened or damaged
immune systems.
 To maintain potency, live attenuated vaccines require refrigeration and protection from
light.
 Examples include Measles/Mumps/Rubella (MMR) and Influenza Vaccine Live, Intranasal
(FluMist®), Polio (Sabin vaccine), Rotavirus, Tuberculosis, Varicella, Yellow fever.
 The attenuated strain of Mycobacterium bovis called Bacillus Calmette- Guérin (BCG) was
developed by growing M. bovis on a medium containing increasing concentrations of bile.
After 13 years, this strain had adapted to growth in strong bile and had become sufficiently
attenuated that it was suitable as a vaccine for tuberculosis.
3. Chimeric vaccine
 The evolution of modern genetic engineering techniques has enabled the creation of
chimeric viruses, which contain genetic information from one viral particle and display the
biological properties of different parent viruses.
 An NIAID-developed live-attenuated chimeric vaccine consisting of a dengue virus
backbone with Zika virus surface proteins is undergoing early-stage testing in humans.
Whole-organism vaccines, whether alive or dead, have another big drawback. Considering
that they are composed of complete pathogens, they retain molecules that are not involved in
 evoking immunity, including unavoidable byproducts of the manufacturing process such as
contaminants that can trigger allergic or immune disruptive reactions.

Subunit Vaccines
 These are vaccines that are prepared by using components or antigens of the pathogen.
These components can stimulate the immune system to elicit appropriate immune
responses.
 They are also known as acellular vaccines because they do not contain a whole cell, but just
part of a cell of the bacteria or virus.
 These vaccines were produced to cub the inefficiencies of the live attenuated and killed
vaccines prepared from whole organisms such as adverse reactions associated with the
vaccines and the mutations that may lead to the virulent strains of the pathogens.
 The subunit vaccines are safe and easier to produce, however, they require the use of an
adjuvant in order to produce a stronger protective immune response. This is because an
antigen alone can not be able to produce sufficiently enough long-term immunity.
 One of the earliest vaccines produced against pertussis was an inactivated Bordetella
pertussis bacteria preparation in the 1940s, but this vaccine caused minor adverse reactions
such as fever and swelling at the injection site, hence the vaccine was avoided leading to a
decrease in its vaccination and therefore an increase in cases of pertussis infections. This
led to the development of acellular pertussis vaccines that were based on purified B.
pertussis components. These newly prepared vaccines had no adverse reactions associated
with their administration.
Some of the subunit vaccines produced to prevent bacterial infections are based on the
polysaccharides or sugars that form the outer coating of many bacteria. Therefore, there are
subtypes of subunit vaccines as follows:

1. Polysaccharide Vaccine
 Some microbes contain a polysaccharide (sugar) capsule which they use for protection and
evading the human immune defenses, especially in infants and young children.
 Therefore, these are vaccines that are prepared using the sugar molecules, and
polysaccharides from the outer layer of a bacteria or virus.
 They create a response against the molecules in the pathogen’s capsule. Normally these
molecules are small hence they are not immunogenic (can not induce an immune response
on their own). Hence, they tend to be ineffective in infants and young children between 18-
24 months, and they induce a short-term immunity associated with slow immune responses,
 and slow activation, and it does not increase antibody levels and it does not create an
immune memory.
 Therefore, these sugar molecules are chemically linked to carrier proteins and work
similarly to conjugate vaccines.
 Examples of polysaccharide vaccines include Meningococcal disease caused by Neisseria
meningitidis groups A, C, W135, and Y, as well as Pneumococcal disease.
Some of the subunit vaccines produced to prevent bacterial infections are based on the
polysaccharides or sugars that form the outer coating of many bacteria. Therefore, there are
subtypes of subunit vaccines as follows:

2. Conjugated Vaccines
 These vaccines are prepared by linking the polysaccharides or sugar molecules on the outer
layer of the bacteria to a carrier protein antigen or toxoid from the same microbe.
 The polysaccharide coating disguises a bacterium’s antigens so that the immature immune
systems of infants and younger children cannot recognize or respond to them.
 Conjugate vaccines get around this problem through the linkage of polysaccharides with a
protein.
 This formulation greatly increased the ability of the immune systems of young children to
recognize the polysaccharide and develop immunity.
 The vaccine that protects against Haemophilus influenzae type B (Hib) is a conjugate
vaccine.
 Today, conjugate vaccines are also available to protect against pneumococcal and
meningococcal infections.

3. Toxoid Vaccines
 These vaccines are prepared from inactivated toxins, by treating the toxins with formalin, a
solution of formaldehyde, and sterilized water.
 This process of inactivation of toxins is known as detoxification and the resultant inactive
toxin is known as a toxoid.
 Detoxification makes the toxins safe to use.
 The toxins used for the preparation of toxoids are obtained from the bacteria that secrete the
illness-causing toxins.
  This means that when the host body receives the harmless toxoid. the immune system
adapts by learning how to fight off the natural bacterial toxin responsible for causing
illness, by producing antibodies that lock onto and block the toxin.
 Examples of toxoid vaccines include diphtheria and tetanus toxoid vaccines.
4. Recombinant Protein Vaccines
 After the start of the generic engineering era, recombinant DNA technology also evolved.
This is where DNA from two or more sources is combined. This technology harnessed the
development of recombinant protein vaccines.
 For recombinant vaccines to induce immunity against a pathogen, they have to be
administered along with an adjuvant or expresses by a plasmid or a harmless bacterial or
viral vectors.
 Production of these recombinant protein vaccines involves the insertion of DNA encoding
an antigen such as a bacterial surface protein, which stimulates an immune response into
bacterial or mammalian cells, expressing the antigen in these cells, and then the antigen is
purified from them.
 Advantages:
 Recombinant protein vaccines allow the avoidance of several potential concerns raised by
vaccines based on purified macromolecules. For example, the presence of contaminants in
vaccines after purification may cause potential harm to the host.
 The production of recombinant vaccines also allows the production of sufficient quantities of
purified antigenic components.
 The classical example of a recombinant protein vaccine currently in use in humans is the
vaccine against hepatitis B. The vaccine antigen is a hepatitis B virus protein produced by
yeast cells into which the genetic code for the viral protein has been inserted.
 Vaccines that are also used to prevent human papillomavirus (HPV) infections are also
based on the recombinant protein antigens, by preparing from the proteins of the outer shell
of HPV, which form particles that almost resemble the virus.
 The virus-like particles (VLPs) prompt an immune response that is similar to that elicited
by the natural virus, and they are non-infectious since they do not contain the genetic
materials that the virus needs to replicate inside the cells.
 An experimental recombinant protein vaccine for chikungunya fever has also been
designed by the National Institute of Allergy and Infectious Disease (NIAID).
 5. Nanoparticle vaccines
 This vaccine development was based on a strategy to present protein subunit antigens into
the immune system.
 The NIAID has also designed a universal flu vaccine, an experimental vaccine with protein
ferritin which can self-assemble into microscopic pieces known as nanoparticles that
display a protein antigen.
 A nanoparticle-based influenza experimental vaccine is also being evaluated in human
trials (early stages).
 This new technology of vaccine delivery is also being evaluated and assessed for the
development of vaccines against MERS coronavirus, respiratory syncytial virus (RSV), and
Epstein-Barr virus.
Recent advances in the subunit vaccine development and delivery systems include solving the
atomic structures of proteins. For example, NIAID has been able to solve the 3-D structure of
a Respiratory Syncytial Virus (RSV) surface-bound to an antibody, identifying a key part of
the protein that is highly sensitive to neutralizing antibodies. They were then able to modify
the RSV protein to stabilize the structural form in which it displays the neutralization-
sensitive site.

 Subunit vaccines are also being developed to offer broad protection against various
infections such as malaria, Zika, chikungunya, and dengue fever.
 The experimental vaccine, designed to trigger an immune response to mosquito saliva
rather than a specific virus or parasite, contains four recombinant proteins from mosquito
salivary glands.
Nucleic Acid Vaccines
 These are vaccines designed to aim at introducing the genetic materials that code the
antigen or the antigen that is aimed at inducing an immune response, enabling the host cells
to use the genetic materials to produce the antigens.
 The advantages of the nucleic acid vaccine approach include:
 stimulating a broad long-term immune response
 excellent vaccine stability
 ease of large-scale vaccine manufacture
 rapid production
 reduces potential risks of working with the live pathogen
 encoding only the key antigen without including other proteins
 The advantage of the ease of production is a potential game-changer for targeting epidemic
or emerging diseases where rapidly designing, constructing, and manufacturing the vaccine
are crucial
Some of the know nucleic acid vaccines models include:

1. DNA plasmid vaccines

 These are vaccines that are composed of a small circular piece of DNA known as a
plasmid. The plasmid carries genes that encode proteins from the pathogen of interest.
 Experimental DNA plasmid vaccines have been designed by the National Institute of
Allergy and Infection Disease (NIAID) to address some viral disease threats including
SARS coronavirus (SARS-CoV) in 2003, H5N1 avian influenza in 2005, H1N1 pandemic
influenza in 2009, and Zika virus in 2016.
2. mRNA vaccines
 mRNA is an intermediary between DNA and protein. Recent technological advances have
developed mRNA vaccines overcoming the instability issues of mRNA and its delivery into
the cells, with encouraging results.
 Some experimental mRNA vaccines have been designed to protect mice and monkeys
against Zika virus infection, and administered in a single dose.
3. Recombinant vector vaccine
 These are vaccines designed as vectors or carriers using harmless viruses or bacterium and
they introduce the genetic material into cells.
 Majorly these vaccines are designed and approved for use to protect animals from
infectious diseases, including rabies and distemper, but some have been developed to
protect humans from viruses such as HIV, Zika virus, and Ebola virus.
Antiviral vaccines

Viral vaccines contain either inactivated viruses or attenuated (alive but not capable of
causing disease) viruses. Inactivated or killed viral vaccines contain viruses, which have lost
their ability to replicate and in order for it to bring about a response it contains more antigen
than live vaccines. Attenuated or live vaccines contain the live form of the virus. These
viruses are not pathogenic but are able to induce an immune response.
 Hepatitis B vaccine (HepB)
 Oral polio vaccine (OPV)
 Measles vaccine
 Rotavirus vaccine
 Yellow fever vaccine