Vaccines
Prevention is always better than cure. And Vaccine development is one such step in this direction to give protection against various bacterial and viral communicable diseases.
Vaccine is a biological substance, dead pathogens or lives but attenuated (artificially weakened) organisms, when introduced into the body prevent the disease produced by those certain pathogens. It’s a mode of acquiring active artificial immunization.
The process of distributing and administering vaccines is referred to as Vaccination. Vaccination and immunization has been used interchangeably in day to day vocabulary.
By vaccination immunity is induced against the pathogen, either by production of antibodies or by activation of T lymphocytes.
These days, lot of vaccines are used to prevent many diseases like measles, mumps, poliomyelitis, tuberculosis, smallpox, rubella, yellow fever, rabies, typhoid, influenza, hepatitis B, etc.
COVID 19 vaccine development is in the human trial phase.
History of Vaccination
Edward Jenner’s in 1796 developed first vaccine and this term vaccine is derived from cow pox (Latin) variola vaccinæ, adapted from the Latin vaccīn-us, from vacca cow). He produced first live attenuated vaccine. He inoculated a young boy in England and successfully prevented him from getting smallpox. Jenner used a lancet to scratch some infected pus material from a woman with cowpox (similar to smallpox but mild form) under the boy’s skin.
In 1885, scientist Louis Pasteur’s experiments spearheaded the development of live attenuated cholera vaccine and inactivated anthrax vaccine in humans (1897 and 1904, respectively).
Characteristics of a good Vaccine
1. Should be safe and have few side effects
2. Give long lasting Immunity
3. Low in cost
4. Stable with long shelf life (No special requirement of storage)
5. Easy to administer
Routes of Administration
Oral Intramuscular
Subcutaneous Intradermal
OPV
DT, DTap, TT
Measles BCG
RotaVirus
Hepatitis B
Yellow Fever
IPV
Hib
Types of vaccine
1. Whole-Pathogen Vaccines
a) Live-attenuated (weakened) vaccines
These vaccines contain modified strains of a pathogen (bacteria or viruses) that have been weakened (attenuated) and avirulent but are able to multiply within the body and remain antigenic enough to induce a strong immune response. Attenuation can often be achieved by growing a pathogenic bacterium or virus for prolonged periods under abnormal culture conditions.
Examples: BCG (Bacillus Calmette Guerin) used in tuberculosis is an example of the attenuated strain of Mycobacterium Bovis. The varicella-zoster vaccine, oral poliovirus (OPV) vaccine, or yellow fever virus vaccines are other such examples of this type of vaccine.
Advantages
• These vaccines are quite potent as they induce the immune system and memory.
• As the pathogens in these vaccines replicate transiently inside the body ( Intracellular), they can induce a good cell mediated response along with good humoral response.
Disadvantages
• Attenuated or Avirulent form may revert back to virulent form
• Can not be administered to immune-compromised individuals.
• Possibility of contamination from other cells in the culture.
• Stringent temperature for storage is a primary requirement
b) Killed-inactivated vaccines
To produce this type of vaccines, bacteria or viruses are killed or inactivated by a chemical treatment, heat or radiation. This group includes the inactivated poliovirus (IPV) vaccine, pertussis vaccine, rabies vaccine, or hepatitis A virus vaccine.
Chemical inactivation can be done with formaldehyde or various alkylating agents. The Salk polio vaccine is produced by formaldehyde inactivation of the poliovirus. Heat inactivation is often unsatisfactory because it causes extensive denaturation of proteins (Epitopes).
Inactivated vaccines usually don’t provide good immunity (protection) like live vaccines as they are weak antigens. Several doses may be needed over a period of time (booster shots). But the safety of inactivated vaccines is greater.
2. Sub-unit vaccines
Subunit vaccines includes only the antigens instead of the entire microbe that best stimulate the immune system. These vaccines use epitopes—the very specific parts of the antigen that antibodies or T cells recognize and bind to. As it contains only the essential antigens and not all the other molecules that make up the microbe, the chances of adverse reactions to the vaccine are lower.
Examples are pneumococcal pneumonia or meningococcal meningitis where polysaccharide fraction of the cell wall of a disease causing organism is used as antigen for the induction of immunity.
3. Toxoid Vaccine
These vaccines are used when a bacterial toxin is the main cause of illness. When the immune system receives a vaccine containing a harmless toxoid (formed by inactivating toxins), it produces antibodies that block the toxin. e.g Vaccines against diphtheria and tetanus also called as Diptheria and tetnus toxoid.
4. DNA Vaccines
Here, the genes for a microbe’s antigens are introduced into the body; some cells will take up that DNA. The DNA then instructs those cells to make the antigen molecules. The cells secrete the antigens and display them on their surfaces.
The DNA of the microbe either integrates into the chromosomal DNA or to be maintained for long periods in an episomal form and is often taken up by dendritic cells or muscle cells in the injection area.
Modrena is one such mRNA vaccine which is being developed in USA and is under phase 3 (human trial).
Thus, the body’s own cells become vaccine-making factories, synthesizing the antigens necessary to stimulate the immune system.
Recombinant Vector Vaccines
Several genes from different etiologic agents have been cloned, expressed and purified to be tested as vaccines. There are a variety of expression systems for antigenic protein components, such as bacteria, yeast, mammalian cells and insect cells, in which the DNA encoding the antigenic determinant can be inserted and expressed.
Individual genes that encode the key antigens of virulent pathogens can be introduced into attenuated viruses or bacteria. The attenuated organism serves as a vector, replicating within the vaccinated host and expressing the gene product of the pathogen. The expressed gene product elicits immune response in the host. They are quite similar to DNA vaccines.
The ChAdOx vaccine, a type known as a recombinant viral vector vaccine, which is under trial for Covid-19, uses a weakened version of the common-cold virus spiked with proteins from the novel coronavirus to generate a response from the body’s immune system.
Recombinant antigen vaccine
Advantages
As most of the genome of the pathogen is missing, reversion potential is virtually eliminated.
Disadvantages
Most of them present weak or poor immunogenicity when given alone, and thereby require the use of adjuvants to elicit a protective and long-lasting immune response
Vaccine Adjuvant
A substance that is added to the vaccine to increase the body’s immune response to the vaccine is vaccine adjunant. Their unique capacity to stimulate both the Th1 immune response and the production of cytotoxic T-lymphocytes (CTLs) against exogenous antigens makes them ideal for use in subunit vaccines and vaccines directed against intracellular pathogens as well as for therapeutic cancer vaccines.
The successful use of recombinant proteins as vaccines, including hepatitis B and HPV become possible when aluminium salt is used as adjuvant.
Saponins, natural glycosides of steroid or triterpene are another pharmacological compounds which can be used as adjuvant. It can activate the mammalian immune system.