Vaccines, Vaccination, Immunization

(Before reading this article, better read articles on Immunology and Immunotechnology, and Monoclonal antibodies, at this website. Also see the article on Cytokines)

Introduction

A number of diseases are caused by micro-organisms. For many bacterial diseases, and some fungal diseases, there are antibiotics, produced by other micro-organisms. There are also chemical agents produced by higher plants that can control microbial pathogens. But there are very few means of fighting viral diseases. Even when there are therapeutic agents to control several microbial diseases, in course of time the pathogen acquires resistance, making the therapeutic agent ineffective. In this eternal race between the pathogen and the pathologist, the pathogens seem to be always a step ahead. Against this background, production of vaccines against the microbial pathogens, and more particularly the pathogenic viruses, in order to immunise the susceptible populations, is a safe and more certain recourse. More importantly, the immunological approach is both preventive and curative, while other means are only curative.

Advances in immunology and biotechnology have made it now possible to produce immunological agents to afford protection from diseases to large numbers of people. This area is immunotechnology, an arm of biotechnology.

Vaccines

A vaccine is an agent, sourced from the pathogen, and is deliberately introduced into the mammalian system in order to impart a ‘memory’ of the pathogen or its pathogenic component. The memory is imparted on the first contact of the vaccine with the mammalian immune system. Vaccine usually contains the modified pathogenic organism or a protein or a low molecular weight non-protein compound (hapten) conjugated with the protein, obtained from the pathogen.

Vaccines contain antigens (that elicit the production of antibodies), or immunogens (that trigger the cellular component of immune response). In the event of an encounter with the corresponding antibodies, only the antigens can bind with the antibodies, and form an antigen-antibody complex that neutralises the harmful effects of the antigens or the organisms that produce them.

Since vaccines employ a part of the chemical machinery of the organisms themselves, pathogens cannot easily acquire resistance to vaccines, as they do for antibiotics and chemical therapeutic agents.

Vaccination/Immunisation

The process of the deliberate introduction of a vaccine into the organism is vaccination, for which the term inoculation is also often used. Since vaccination immunises the organism, the process is also called immunisation.

When an organism is vaccinated, the immune system is readied to show an immune response by way producing antibodies against the pathogen, in the event of a second encounter with the pathogen, basing on the memory imparted by the vaccine used for the first encounter.

Immunotherapy

Immunotherapy differs from vaccination in that in the former antibodies isolated from an immunised organism (polyclonal or monoclonal immunoglobulin antibodies or cytokines) is used to cure the patient. Immunotherapy becomes essential when there is no time to prepare the patient through vaccination or when the patient is physically and/or physiologically not competent to respond to vaccination.

Composition of vaccines

Vaccines are suspensions, in saline or buffered saline, of weakened pathogenic organisms or their fractions or the proteins they secrete, which have the potential to cause a disease. A virulent organism cannot be used as a vaccine.

Adjuvants

Antigens often need to be coupled with an adjuvant, which is a compound that holds the antigen and releases it slowly over a longer period of time. The most commonly used immunological adjuvant in experimental systems is Freund’s Complete Adjuvant, which contains mineral oil and heat killed mycobacteria. The bacteria are intended to heighten immunological response, but may produce hypersensitivity in many patients. The mineral oil also may prove to be harmful. Hence FCA is not normally used in human immunisation schedules. Aluminium hydroxide is human safe but is a poor adjuvant. Some plant saponins are now projected as efficient and human safe adjuvants. There are some effective and safe synthetic adjuvants, but their composition is a trade secret.

Types of vaccines

a) Inactivated vaccines: The pathogen is killed using heat or formalin, as for example, typhoid or Salk poliomyelitis vaccines.

b) Attenuated vaccines: The pathogen is weakened (attenuated) by aging or altering growth conditions, but is alive, as in the case of measles, mumps and rubella vaccines. There is some risk of the concerned virus becoming virulent.

c) Avirulent organisms: A non-pathogenic strain of a pathogenic organism is used as a vaccine, as in BCG (Bacillus Calmette Guerin) vaccine against Mycobacterium tuberculosis, the tuberculosis bacterium.

d) Toxoids: The toxin from the pathogen is used as an antigen to produce the vaccine. The severity of the toxicity of the antigen is reduced by treating it with aluminium salts while preparing the ‘toxoid’, as in the case of diphtheria and tetanus.

In the case of allergy, the allergenic proteins from pollen and other allergenic material are isolated and used to immunise the patient.

e) Acellular vaccines: Only the antigenic component of the organism is used instead of the whole organism, as in Haemophilus influenza B vaccine.

f) Subunit vaccines: Genetic engineering techniques have now made it possible to use as a vaccine only a part of an organism that is adequate to stimulate the immune response. An appropriate segment of genetic material is isolated from the pathogens and introduced into bacteria or yeasts, to transcribe and translate the inserted foreign DNA. The product is used as a vaccine, as in the case of Hepatitis B vaccine. These vaccines cannot cause the disease even in patients whose immunological system is impaired (immunocompromised) patients.

g) DNA vaccines: Described as the third vaccine revolution, DNA vaccines are an offshoot of gene therapy. Selected segments of DNA, when introduced into the patients system synthesise and deliver proteins that are needed to replace the defective enzyme system or tag a cell for destruction. Viruses or lipid vehicles are used to deliver the DNA into the cells. This recent technology is being tried to produce vaccines against HIV, by a direct injection of plasmid borne DNA.

Herd immunity

Use of vaccines to prevent disease in communities is herd immunity, which affords protection by decreasing the number of susceptible people in a community, with time. This basically constitutes mass immunisation. Polio vaccination programmes now target an enormous number of children throughout the world, to eradicate polio, as was done for smallpox earlier.

Booster doses

The effectiveness of certain vaccines is life long as for example of smallpox, measles, mumps and rubella. Attenuated vaccines normally afford life long immunity. But in the case of certain others, the effectiveness is short lived and the immune system needs to be re-educated through periodical booster doses. The vaccine is administered one or more times, with appropriate time gaps, after the initial vaccination, to boost to the immune system to produce adequate quantities of antibodies against the intended pathogen. Toxoid vaccines require a booster every ten years or so. Booster doses are also needed in case of inactivated or acellular vaccines, which are very safe, as they cannot cause the disease.

Multiple vaccines

While most vaccines contain antigens of a single pathogen, there is a practice of multiple vaccines, which combine antigens of more than one pathogen. For example, diphtheria, tetanus and pertussis are administered together as DTP vaccination.

Vaccine administration

Vaccines are administered, as injections (DTP), or dermally (smallpox, anthrax), or orally (polio) or as a nasal spray (influenza virus).

Edible vaccines

Now transgenic plants are being developed through genetic engineering techniques, where the vaccine is synthesised in the edible part of a food plant (edible vaccines). Transgenic bananas, melons, and tomatoes are choice candidates for carrying edible subunit vaccines, as for example against rabies. The obvious advantage is the ease of transportation and storage of the vaccine bearing material and administration without technical support. Conventional vaccination programmes in many countries are seriously handicapped due to a lack of equipment for storage and transport of the vaccines and the shortage of paramedical staff to administer the vaccines.

Safety of vaccines

By and large vaccination programmes have proven to be reasonably safe for the human populations. However, at certain times complications may arise mostly due to an incorrect handling of the vaccines and/or vaccination or due to individual metabolic deficiencies. In spite of all that is adverse in vaccination, immunisation is one of the most efficient means of disease prevention, particularly in large sections of the human population. In the case of HIV and epidemic diseases and even cancer, immunisation is probably the only hope.