Vaccination

regarded as one of the most beneficial pharmaceutical interventions due to its ability to induce protection against infectious diseases through targeted activation of the human immune system.

What is a Vaccine?
A vaccine is a non-pathogenic antigen that mimics a particular pathogen in order to elicit an immune response as if that actual pathogen were in the body.
The overall goal of a vaccine is to establish immunity against that particular pathogen.

Vaccine development
Edward Jenner
in 1796, used cowpox to provide immunity to small pox

Robert Koch
In 1876, developed a series of experimental steps called postulates that could be used to determine the cause of a disease

Louis Pasteur
developed vaccines for rabies (1885) and anthrax

Jonas Salk/ Albert Sabin

Salk developed injectable vaccine for polio (1955) Sabin developed an oral vaccine (1961)

Types of immunization
Active immunization.
Involves administration of an antigen to an animal so that it mounts an immune response. Re exposure to infection will result in a secondary response.

Types of Immunization.
Passive immunization
Temporary Transferring antibodies from a resistant to susceptible animal. Immediate protection. Gradually get catabolised. Susceptible to reinfection.

Active immunity 1.Attenuated Virus/Bacteria

These vaccines consist of live, but weakened, viruses or bacteria. These organisms have been altered, either genetically or chemically, in a way that they are not pathogenic. An example is the attenuated virus vaccine for yellow fever, which utilizes the YF17D strain, a weakened form of the wild virus.

2.Killed Whole Organism

This vaccine consist of the actual pathogen, however, it has been killed, either by a heat treatment or chemically. An example is the Salk vaccine for polio, which utilizes whole polioviruses that have been inactivated by formaldehyde.

Passive Immunity. 1.Toxoids

Some bacterial produce exotoxins. Toxoids are vaccines which consist of exotoxins that have been inactivated, either by heat or chemicals. These are intended to build an immunity against the toxins, but not necessarily the bacteria that produce the toxins. Some examples are botulinum antitoxin and diphtheria antitoxin.

2.Surface Molecules
Proteins, carbohydrates, and lipids Proteins complex enough to be used on there own. Carbohydrates and lipids requires conjugated with a large protein in order to be immunogenic. An example ,hepatitis B surface antigens.

Modern Vaccine Technologies

Although killed and modified live vaccines have been successful. There is need to make them more cheap,effective and safer.

DNA Vaccines
Plasmids that contains genes for certain types of antigens. The genes are expressed in target cell. Target cell either excretes the antigen or displays it on an MHC-I molecule. Vaccines for CPV,NCD,FMD etc. For dangerous to grow in laboratory.

Genetically Attenuated Vaccines

Consist of attenuated viruses that have been engineered by removing genes of pathogens. Available against herpesvirus (Gene coding for thymidine kinase has been removed which is essential for replication)

Antigens Generated by Gene Cloning.

DNA coding for gene of an antigen of interest is first isolated. This inserted into a bacterium or other cell and the recombinent antigen is expressed. First sucessful gene cloning was done in case of FMD disease virus.

Fig. Production of recombinant viral protein for use in vaccine

Live virus

Exised viral gene inserted in plasmid

Transformed cell

Secreted protein

Infect

Infect Inject

Purify & conc.

Not protected

Protected!

Vector vaccines(Live recombinant organisms)

Cloning of the gene coding for protein antigens Recombinant organisms are used. Viruses like adenovirus,herpesvirus have been used. The vaccinia virus has been widely used. An example for such vaccine is vaccinia virus recombinant which contains gene for rabies envelope glycoprotein (G-protein)

Vector vaccines(Live recombinant organisms)

Chimeric Vaccines
Consist of attenuated viruses those carry antigens from multiple types of pathogens. The yellow fever vaccine YF17D has been engineered to carry antigens from HIV, different types of bacteria, malaria, even cancer. The aim of a chimeric vaccine is the establishment of immunity against several different diseases with one administration.

Empty Capsids as Vaccines

Production of empty capsids from whole virus is cucumbersome and not practical. However it has been shown that plasmid encoding Porcine GM-CSF together with a FMD empty capsid appeared to improve FMD specific antibody production.

Synthetic peptide vaccines

If the structure of epitope is known Chemical synthesis of epitope and used as a vaccine Complete sequencing of antigen and identification of its epitopes can be predicted by computer models or by monoclonal antibodies. Developed for hepatitis B,FMD,CPV and influenza virus.

In-Vivo
The vaccine is produced inside a living organism. Embryonated Chicken eggs. anti-idiotype vaccines, can also be produced in lab animals, such as mice. Some species of plant, such as bananas, that have been genetically engineered to produce a vaccine.

In-Vitro
Using recombinant DNA technology, vaccines can be produced in yeast cultures, bacterial cultures, or cell cultures. Attenuated virus/bacteria vaccines can also be produced this way.

Chemical Synthesis
Here, instead of using biological systems can be produced in a lab. Vaccines that utilize synthetic peptides as well as conjugated lipids and polysaccharides are manufactured this way. Usually, this method is used in combination with either in-vivo or in-vitro production.

Adjuvants.
An adjuvant is a chemical substance that can be added to a vaccine in order to enhance the immune response to the vaccine. There are three types of adjuvants.

Aluminum Hydroxide and Aluminum Phosphate (Alum)

Binds to proteins and causes them to precipitate. Whenever the alum/vaccine complex is injected into the body, it slowly dissolves, releasing the vaccine. Bacterial extracts can be added, which enhances the immune response. Alum is the only adjuvant approved for use in humans.

Freunds Adjuvant
The vaccine is suspended in oil droplets. When injected into the body, the vaccine slowly diffuses out of the oil drop. Bacterial antigens can be added in order to enhance the immune response. Not used in humans because of risk of severe inflammation.

Immune Stimulatory Complexes

Consists of open cage-like structures that contains cholesterol and a mixture of saponins. Allows delivery of the vaccine to the cytosol, which stimulates a response by cytotoxic T-cells . Such an adjuvant may be particularly useful in a vaccine against cancer.

The Mechanism of a Vaccine

In an ideal scenario, whenever a vaccine is first administered, it is phagocytized by an antigen presenting cell (APC). Recent research suggest that it is particularly important that the vaccine be taken up by a dendritic cell. This is because dendritic cells play a key role in activating T cells, which become helper T cells (Th cells).

 From there, the activated Th cells goes on to activate mature B-cells. These activated B-cells divides into two cell types, antibodyproducing plasma cells and, most importantly, memory B cells. Memory T-cells are also established, however, they usually have a shorter half-life than memory B cells, thus, they play only a minor role in longterm immunity. Usually, there are no cytotoxic T-cells formed whenever the body responds to a vaccine.

Preservatives.
Used to prevent contamination Thimerosal -widely used. Some use 2-phenoxyethnol to prevent contamination of gram negative bacteria.

Edible vaccines.
Significant possibilities of reducing the burden of diseases like hepatitis and diarrhoea