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Vaccination (Active Immunoprophylaxis)
المؤلف:
APURBA S. SASTRY , SANDHYA BHAT
المصدر:
Essentials Of Medical Microbiology 2021
الجزء والصفحة:
3rd edition , p222-224
2025-10-13
34
Vaccine is an immunobiological preparation that provides specific protection against a given disease. Following vaccine administration, the immunogen (active ingredient of the vaccine) stimulates the immune system of the body to produce active immunity in the form of protective antibody and/or immunocompetent T cell response.
- History: The terms vaccine and vaccination are derived from ‘Variolae vaccinae’ (smallpox of the cow), the term devised by Edward Jenner to denote cowpox. Later, Louis Pasteur proposed the term ‘vaccine’ to cover all the new protective preparations being developed, in the memory of Edward Jenner
- Valency: Vaccines may be monovalent that contains single antigen or single serotype of a microorganism) or polyvalent (contains two or more strains of the same microorganism), e.g. trivalent vaccines such as influenza vaccine and polio vaccine
- Homologous and heterologous vaccine: In most vaccines, the immunizing substance is derived from the same microorganism against which it is used (homologous vaccine). However, there are few exceptions, where the vaccine organism is different from the disease-causing organism. Such vaccines are called as heterologous or “Jennerian” vaccines. Examples include—
* The classic example is Jenner’s use of cowpox to protect against smallpox
* Use of BCG vaccine made from Mycobacterium bovis to protect against human tuberculosis caused by M. tuberculosis.
- Types: Vaccine may be prepared by live modified organisms, inactivated or killed organisms, extracted or cellular fractions, toxoids or combinations of all these. Preparations that are more recent are subunit vaccines and recombinant vaccine. Vaccines of future prospects include DNA vaccine and edible vaccine.
Live Attenuated Vaccine
Live vaccines, such as BCG (Table 1) are prepared from live (usually attenuated) organisms.
- The live attenuated organisms lose their ability to induce full blown disease, but retain their immunogenicity
- Attenuation is achieved by passing the live organisms serially through a foreign host, such as chick embryo/ tissue culture or live animals.
Note: Smallpox vaccine is a live vaccine which is not attenuated. The nonpathogenic cross reactive vaccinia virus or cowpox virus were used to vaccinate against smallpox virus (i.e. variola)
Table1. example of commonly used vaccines.
Advantages
Live vaccines in general, are more potent immunizing agents compared to killed vaccines, due to the following reasons:
- The live organisms multiply in the host and the resultant antigenic dose would be larger than what is administered
- Live vaccines retain all the immunogenic components (major and minor) of the organisms
- They are capable of inducing mucosal immunity by stimulating secretory IgA antibody production at the local mucosal sites.
Precautions While Using Live Attenuated Vaccines
- Contraindications: Live vaccines should not be administered in individuals with immunodeficiency diseases or any conditions that suppresses the immunity, such as leukemia, lymphoma, malignancies, on corticosteroid or any other immunosuppressive drug therapy
- Pregnancy is another contraindication, unless the risk of infection exceeds the risk of harm to the fetus by giving the live vaccine
- When two live vaccines are required to be given; they should be administered with an interval of at least 4 weeks. Exception is yellow fever vaccine which can be given less than 4 weeks after MMR vaccine
- Dosage: Most live vaccines are given in single dose format as effective immunity is achieved with a single dose. Exception is oral polio vaccine (OPV) which is given as multiple doses at spaced intervals to achieve effective immunity
- Risk of gaining the virulence: The attenuation of the live vaccine has to be done in an effective way otherwise there is always a risk of gaining the virulence back
- Storage: Live vaccines must be stored cautiously to retain effectiveness, especially the OPV and measles vaccine.
Inactivated or Killed Vaccine
It consists of organisms, which are grown in culture under controlled conditions and then killed using methods, such as heat or formaldehyde.
- They are generally safer but less efficacious than live vaccines
- Compared to the live vaccines, killed vaccines require large doses, adjuvants, and multiple doses to confer immunity. In most cases, a booster dose is also needed
- Adjuvants increase the immunogenicity of the vaccine antigen (e.g. alum is used as adjuvant in DPT vaccine)
- Killed vaccines are usually administered in subcutaneous or intramuscular routes. The only absolute contraindication is a severe local or general reaction to the previous dose.
Various characteristics of killed and live vaccines are given in Table 2.
Table2. Characteristics of killed and live vaccines.
Toxoid Vaccine
The exotoxins produced by certain bacteria can be detoxicated to form toxoid by treating with acidic pH, formalin or by prolonged storage.
- Toxoid is a form of toxin that loses its virulence property but retains immunogenicity
- When a toxoid preparation is given as vaccine, it induces formation of neutralizing antibodies that are capable of neutralizing the toxin moiety produced during an infection; rather than acting upon the organism
- Examples include diphtheria toxoid (from Corynebacterium diphtheriae) and tetanus toxoid (from Clostridium tetani).
Extracted or Cellular Fractions Vaccine
Vaccines, in certain instances, are prepared from extracted cellular fractions; examples include meningococcal vaccine, pneumococcal vaccine and Haemophilus influenzae type b vaccine—all are prepared from the capsular polysaccharide antigens of the respective organism.
Subunit Vaccines
For certain viruses, only a particular subunit of the virus is necessary to initiate the immunity, e.g. hepatitis B surface antigen (HBsAg) is the immunogenic component of hepatitis B virus. So, this viral component alone can be used as vaccine rather than the whole virus.
- Examples of subunit vaccines include hepatitis B vaccine and human papillomavirus (HPV) vaccine
- DNA recombinant technology is used for the preparation of such sub viral components. For example, in hepatitis B vaccine preparation, the gene coding for HBsAg is inserted into the chromosome of baker’s yeast, so that, with the multiplication of the yeast, the gene of interest would also replicate resulting in production of large quantity of HBsAg which can be used as vaccine.
Combinations
If more than one immunizing agents are included in a vaccine preparation, it is called combined vaccine. The aim of the combined vaccine is to—
- Simplify administration and
- Augment the immunogenicity of the immunogen. For example, in DPT vaccine, the pertussis component acts as an adjuvant, which increases the immunogenicity of both diphtheria toxoid and tetanus toxoid.
Newer Vaccine Approaches
DNA Vaccine
DNA vaccines are experimental at present, have many advantages such as cost effectiveness and mounting a stronger and wider range of immune response.
The small pieces of DNA containing genes from the pathogenic microorganism are injected into the host. The gene of interest gets integrated with the host cell genome and starts transcribing the proteins against which the host mounts an immune response. Several vaccine trials are going on based on DNA vaccines.
Edible Vaccine T he edible vaccine is a new concept introduced recently.
- The gene encoding the orally active antigenic protein is isolated from the pathogen and is transferred to suitable plant bacteria, which are then used to infect a transgenic plant (e.g. banana, potato, etc.)
- The plants infected by the bacteria then start producing the antigen of interest in large scale. The appropriate plant parts having the antigen may be fed raw to animals or humans to bring about immunization
- The advantages of the edible vaccines are—(1) low cost, (2) ability to produce in large scale, (3) administered orally, (4) induce local immunity, and (5) heat stable
- Applications: The edible vaccines are still under experimental stage; some formulations available include—
* Transgenic potatoes and tomatoes against diarrhea genic organisms
* Edible banana against Norwalk virus.
Cold Chain
“Cold chain” refers to a system of transport, storage, and handling of vaccines, starting at the manufacturer level and ending with the site of administration of the vaccine to the client. The optimum temperature for refrigerated vaccines is between +2°C and +8°C. For frozen vaccines the optimum temperature is –15°C or lower. In addition, protection from light is a necessary condition for some vaccines. Improper cold chain maintenance is one of the most common causes of vaccine failure; especially oral polio vaccine which is the most sensitive vaccine to heat; must be stored at –20°C.
- Vaccines which must be stored in the freezer compartment are polio and measles vaccines
- Vaccines which must be stored in the COLD part but never allowed to freeze are—DPT, TT, Td, BCG, hepatitis B, H. influenzae type b and diluents.
Vaccine Vial Monitor
Vaccine vial monitor is a tool to monitor the stability/potency of a vaccine and to check the efficiency of cold chain.
It is heat sensitive label lining the vaccine vial. It contains an outer blue circle and an inner white square. With time and exposure to higher temperature, the inner square changes its color gradually from white towards blue, whereas the outer circle is not heat sensitive; it remains blue throughout (Table 3 and Fig. 1).
Table3. Staging of vaccine vial monitor.
Fig1. Various stages of vaccine vial monitor (Vaccine is usable up to stages I and II and should be discarded for stages III and IV) Source: Pondicherry Institute of Medical Sciences (with permission).
National Immunization Schedule 2020 (NIS)
Immunization is one of the most logical and cost effective strategies of any country for the prevention of childhood sicknesses and disabilities and is thus a basic need for all children. The following is the national immunization schedule recommended by the Ministry of Health, Government of India and it includes those vaccines that are given free of cost to all children of our country (Table 4).
Table4. national Immunization Schedule 2020 (NIS) for infants, children and pregnant women.
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