Vaccines- Definition, Principle, Types, Examples, Side Effects

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

According to the CDC, a vaccine is a preparation used to stimulate the body’s immune response against diseases. Vaccines are usually administered through needle injections, but some can be administered by mouth or sprayed into the nose.

• 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.
• In 1885, Louis Pasteur successfully prevented rabies through post-exposure vaccination. The treatment is controversial. Pasteur has unsuccessfully attempted to use the vaccine on humans twice before, and injecting a human with a disease agent is still a new and uncertain method (Source: WHO)
• 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.

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.

Side Effects of Vaccines

• The effects of vaccines are normally mild and go away within hours to days of administration. Intravenously administered vaccines can leave a sore pain on the site of administration but it goes away after a few hours or days, on their own.
• However, the effects may vary from individual most side effects of vaccination can be mild including soreness, swelling, or redness at the injection site, fever, rashes, and achiness to serious effects including seizure or life-threatening allergic reactions, but they are rare.
• Many infants and children will experience a medical event in close proximity to vaccination, which may or may not be related to vaccination. According to the Food and Drug Administration (FDA) and the Center for Disease Control (CDC), monitoring and analyzing the adverse effects of vaccination in children.
• Some of the mild effects include:
  • Pain, swelling, or redness where the shot was given which may last 2-4days
  • Mild fever and chills that lasts for a few hours and it occurs in 70% of all the vaccinated children
  • Fatigue
  • Headaches
  • Muscle and joint aches
  • Fainting
• Note that, some of these effects arise as a sign of the bodybuilding up immunity against a disease.
• Serious or adverse side effects are rare but may occur in 1 to 1million people, and they may include:
  • Serious eye infection, or loss of vision, if the vaccine spreads to the eye eg smallpox vaccine.
  • Rashes may occur on the entire body in 1 per 4,000 people.
  • Severe rash on people with eczema in 1 per 26,000.
  • Severe brain reaction or Encephalitis can lead to permanent brain damage occurring in 1 per 83,000.
  • Severe infection begins at the site of vaccination occurring in 1 per 667,000, mostly in people with weakened immune systems.
  • Death occurs in 1-2 per million, mostly in people with weakened immune systems.
• For every million people vaccinated for smallpox, between 14 and 52 could have a life-threatening reaction to the smallpox vaccine.
• Examples of vaccines and their effects
  • Haemophilus influenza type B vaccine is well known for its potential side effects. Haemophilus influenza type B is a bacterium that can cause serious infections, including meningitis, pneumonia, epiglottitis, and sepsis, and it is recommended that children receive the Hib vaccination as early as 2 months old. Some of the known side effects include:
  • Redness, warmth, or swelling where the shot was given (up to 1 out of 4 children)
  • Fever over 101°F (up to 1 out of 20 children)
• Smallpox is a fatal infection that has a 30-40% fatality rate and it is caused by Variola major or Variola minor virus its vaccination is done mainly to military personnel and people who are first responders in the event of a bioterror attack. Some of the side effects of the smallpox vaccine include rashes, redness, and tenderness on the site of administration, fever, headaches, loss of vision, brain damage (encephalitis), and even death.

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