Sunday, February 9, 2014

Vaccines and biological therapy

Disease prevention is the key to public health. Immunization is the means of providing specific protection against most common and contagious  pathogens. vaccination is called active immunization because the immune system is stimulated to develop its own immunity against the pathogen. Vaccination is a much safer way to induce immunity, which provide artificially acquired immunity. Vaccines cannot only prevent a disease from occurring but also decrease the risk of complications and risk of transmission. Every year vaccines prevent up to 3 million deaths and save 750,000 children from disability.Vaccines are a safe, cost-effective, and efficient way to prevent sickness and death from infectious diseases.

 Discovery of  Vaccines

The word vaccine is derived from the word vaca, meaning a cow in Spanish. Edward Jenner discovered a vaccination for smallpox disease in 1796. Jenner used cowpox to protect against small pox. Jenner scratched some pus from a Cowpox sore into the arm of a boy James Phipps to see whether exposure to the virus protect the child from the smallpox virus. Phipps was became immune, proving that inoculation with cowpox provided resistance against smallpox. Louis Pasteur performed first experiment in immunology in July 6,1885. Louis Pasteur treated a boy against rabies by injecting spinal cord fluid of a rabid dog. The spinal cord fluid stimulated the production of antibodies against the rabies virus. During 1950 to 1970, vaccines for polio, measles, mumps and rubella was developed. This period is called Golden age of vaccine technology

Principle of vaccine 

 A vaccine stimulates the antibody production and formation of memory cells without causing  the disease.  Vaccines are cheap, cost – effective , easily administered and adoptable to mass immunization. In general, Vaccines are  thoroughly tested and monitored.  Vaccines  provide  protective immunity and immunological memory  to individuals, families and communities  against any infectious disease. Vaccines stimulate both cell mediated and humoral immunities. Generally viral diseases are managed through vaccination. Vaccines are effective in preventing disease not only in individuals, but also in communities. This type of protection is called "herd immunity."

Strategies of disease prevention by vaccines
 Primary prevention  is an intervention before the biologic onset of disease e.g. prevention of infectious disease by vaccination. Secondary prevention  is an intervention when disease can be detected at a stage before it becomes  symptomatic e.g. AIDS.

Kinds of Vaccines 

Prophylactic vaccines  are used to prevent the effects of a future infection by any natural or wild pathogen. e.g. anti-rabies vaccine.
Therapeutic vaccines  are devised to harness the immune response to treat diseases ranging from cancer to multiple sclerosis. E.g. cancer vaccine.
Monovalent (univalent) vaccines are designed to immunize against a single antigen or single pathogen. E.g. chicken pox.
Multivalent (polyvalent) vaccines are designed to immunize against two or more strains of the same microorganism or against two or more microorganisms. E.g. DTP vaccine – (Diphtheria- tetanus- pertussis  vaccine). MMR vaccine – measles-mumps-rubella vaccine.

Kinds  of traditional vaccines 

1.Killed (inactivated) Whole cell  vaccines 
The inactivation process is aimed at destroying the pathogenicity of the  microorganism while retaining its immunogenicity. Usually the pathogenic viruses are chemically inactivated.  Killed vaccines induce higher antibody titres  but not effective as live vaccines. Killed vaccines are safe with respect to residual virulence. Since antibody titres diminish with time, repeated vaccinations are required. E.g.Viral vaccines- polio, hepatitis A, rabies, influenza ; Bacterial vaccines – pertussis, typhoid, cholera, plague
2. Live attenuated(weakened) vaccines 
The live vaccine usually contains an attenuated non-pathogenic microorganism able to replicate in the host and produce long term protective immunity. Single dose is effective. No booster dose is required. Live microorganism tends to survive longer  in the host and provide a wide range of immune responses. E.g.Viral vaccines – measles, mumps, rubella, vaccinia,  varicella / zoster, yellow fever, oral polio; Bacterial vaccines-BCG, Oral typhoid.
3. Toxoids (inactivated toxins)
 The toxins of microorganisms are treated  with formalin and incubated at 37 0C for 3- 4 weeks. The denatured  toxin  is called a ‘toxoid’.  Toxoids  induce low levels of immune response and are often administered with an adjuvant. Toxoid vaccines often require a booster every ten years. Toxoids e.g. the diphtheria and tetanus vaccines are usually combined with pertussis vaccine as DPT immunization. When more than one vaccine is administered together it is called ‘conjugated vaccine. E.g. Diphtheria vaccine,Tetanus vaccine; 
4. Subunit vaccines (purified immunogenic proteins)
Biotechnology and genetic engineering techniques have been used to produce "subunit vaccines". To create a subunit vaccine, researchers isolate the  genes which code for appropriate subunits from the genome of the infectious agent. This genetic material is placed into bacteria or yeast host cells which then produce large quantities of subunit molecules by transcribing and translating the inserted foreign DNA. These subunit molecules are isolated, purified and used as a vaccine.  e.g. Hepatitis B vaccine.
5. DNA vaccines 
With DNA vaccines, the individual  is not injected with the antigen but with DNA encoding the antigen. The DNA is incorporated in a plasmid containing  DNA sequences encoding one or more protein antigens. DNA sequences are  incorporated with  a promoter  that will enable the DNA to be efficiently transcribed in the human cells. The DNA vaccine can then  be injected into a muscle just as conventional vaccines. DNA vaccines elicit cell-mediated  and antibody-mediated  immune responses. DNA vaccines has been  developed against tuberculosis, SARS, smallpox, and other intracellular pathogens.
Properties  of an ideal vaccine 
The vaccine  should  provide long lasting immunity. It should  induce both humoral and cell mediated immunity. It should not induce autoimmunity or hypersensitivity reactions. It should be inexpensive to produce, easy to store and administer. It should be safe  and effective.
Problems in vaccine development 
Many kinds of viruses may cause similar diseases. e.g. common cold. A single vaccine may not prevent such diseases. Diseases caused by RNA viruses may not be controlled because of  antigenic drift and shift. Diseases  present in large animal  reservoirs may re-infect after elimination from the human population. Integration of viral DNA into host chromosomes may cause problems. There is possibility of recombination and mutation of attenuated viruses in vaccines.

Vaccines of the future

Edible vaccines 
Edible vaccines are cheaper and easier way to immunize people against diseases. It involves introduction of selected desired genes into plants and then inducing these altered plants (GM plants) to manufacture the encoded proteins. The antigens in transgenic plants are delivered through bio-encapsulation. Edible plants are very effective as a delivery vehicle for inducing oral immunization. Edible vaccines are composed of antigenic proteins and do not contain pathogenic genes.

Cancer Vaccines 

Biological therapy involves the use of living organisms or substances derived from living organisms to treat a disease. Biological therapies for cancer use vaccines or bacteria to stimulate the body’s immune system to act against cancer cells. These types of biological therapy, are referred to as “immunotherapy”. Cancer treatment vaccines contain cancer-associated antigens to enhance the immune system’s response to a patient’s tumor cells. Oncolytic virus therapy is an experimental form of biological therapy that involves the direct destruction of cancer cells. Oncolytic viruses infect both cancer and normal cells, but they have little effect on normal cells. In contrast, they readily replicate or reproduce, inside cancer cells and ultimately cause the cancer cells to die.

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