IMMUNOLOGICAL BASES OF VACCINATION AND REASONS FOR LACK OF VACCINE AGAINST HIV VIRUS


IMMUNOLOGICAL BASES OF VACCINATION AND REASONS FOR LACK OF VACCINE AGAINST HIV VIRUS Lana  

4 years ago

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INTRODUCTION
 
Immunology of vaccination
A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe. The agent stimulates the body's immune system to recognize the agent as foreign, destroy it, and "remember" it, so that the immune system can more easily recognize and destroy any of these microorganisms that it later encounters.

Mechanism of function
Generically, the process of artificial induction of immunity, in an effort to protect against infectious disease, works by 'priming' the immune system with an 'immunogen'. Stimulating immune responses with an infectious agent is known as immunization.

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Vaccination includes various ways of administering immunogens.

Some vaccines are administered after the patient alreadySome vaccines are administered after the patient already has contracted a disease. Vaccines given after exposure to smallpox, within the first three days, are reported to attenuate the disease considerably, and vaccination up to a week after exposure probably offers some protection from disease or may modify the severity of disease (en.wikipedia.org/wiki/Vaccination).

Classification of vaccines

There are two basic types of vaccines: live attenuated and inactivated. Live attenuated vaccines are produced by modifying a disease-producing (“wild”) virus or bacteria in a laboratory.

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The resulting vaccine organism retains the ability to replicate (grow) and produce immunity, but usually does not cause illness. Live attenuated vaccines include live viruses and live bacteria.

Live attenuated vaccines

Live vaccines are derived from “wild,” or disease-causing, virus or bacteria. These wild viruses or bacteria are attenuated, or weakened, in a laboratory, usually by repeated culturing. In order to produce an immune response, live attenuated vaccines must replicate (grow) in the vaccinated person.

Although live attenuated vaccines replicate, they usually do not cause disease, such as may occur with the natural (“wild”) organism. When a live attenuated vaccine does cause “disease,” it is usually much milder than the natural disease, and is referred to as an adverse reaction.

Live attenuated vaccines are labile, and can be damaged or destroyed by heat and light. They must be handled and stored carefully.
 Live attenuated bacterial vaccines include BCG and oral typhoid vaccine. Viruses (oral polio, measles, mumps, rubella, yellow fever), Bacteria (BCG, cholera).

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Inactivated vaccines

These vaccines are produced by growing the bacteria or virus in culture media, then inactivating it with heat and/or chemicals (usually formalin). In the case of fractional vaccines, the organism is further treated to purify only those components to be included in the vaccine (e.g., the polysaccharide capsule of pneumococcus). Inactivated vaccines are not alive and cannot replicate. The entire dose of antigen is administered in the injection. These vaccines cannot cause disease from infection, even in an immunodeficient person.

Currently available inactivated vaccines are limited to inactivated whole viral vaccines (influenza, polio, rabies, and hepatitis A). Whole inactivated bacterial vaccines include pertussis, typhoid, cholera, and plague. “Fractional” vaccines include subunits (hepatitis B, influenza, acellular pertussis), and toxoids (diphtheria, tetanus).

Polysaccharide vaccines

Polysaccharide vaccines are a unique type of inactivated subunit vaccine composed of long chains of sugar molecules that make up the surface capsule of certain bacteria.

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Pure polysaccharide vaccines available include: pneumococcal, meningococcal, and Salmonella typhi. The immune response to a pure polysaccharide vaccine is typically T-cell independent, which means that these vaccines are able to stimulate B-cells without the assistance of T-helper cells.

Conjugate vaccines

In the late 1980s, it was discovered that the problems with polysaccharide vaccines could be overcome through a process called conjugation. Conjugation changes the immune response from T-cell independent to T-cell dependent, leading to increased immunogenicity in infants and antibody booster response to multiple doses of vaccine. The first conjugated polysaccharide vaccine was for Haemophilus influenzae type b (Hib).

Also now available are conjugate vaccines for pneumococcal disease and meningococcal disease.

Recombinant vaccines

Vaccine antigens may also be produced by genetic engineering technology. These products are sometimes referred to as recombinant vaccines. There are four genetically-engineered vaccines are currently available:

•    Hepatitis B

•    Human papillomavirus

•    Live typhoid vaccine (Ty21a)

•    Live attenuated influenza vaccine (LAIV)

(www.immune.org.nz/types-vaccines)


INTRODUCTION TO HIV

AIDS was recognized as a novel clinical entity in 1981–1982, when the association of severe immunodepression with increased incidence of Pneumocystis carinii pneumonia and Kaposi’s sarcoma in homosexual men was first recognized as representing possible variations in the spectrum of a new immunodeficiency disease.

The infectious nature of the syndrome was established in 1983, when Drs. Franc¸oise

Barre-Sinoussi and J.

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C. Chermann, at the Pasteur Institute in Paris, isolated a new retrovirus from the lymph node of a patient with disseminated lymphadenopathy and other symptoms that usually precede the development of AIDS. The new virus was initially named lymphadenopathy-associated virus (LAV) and later received the designation of HIV. HIV belongs to the Lentiviridae family of retrovirus.

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Two major variants of the virus have been identified. HIV-1, the first to be isolated, exhibits remarkable genetic diversity, and the different variants have been grouped into seven different families or clades, differing by 30% to 35% in their primary structures. HIV-2, prevalent in West Africa, was isolated a few years later. HIV-2 is less virulent than HIV-1, rarely causes a full-blown AIDS syndrome, and it is not spreading so widely and rapidly as HIV-1. Both viruses are derived from simian immune deficiency virus (SIV) and there is now strong genetic data to support that HIV is derived from the chimpanzee form of SIV. (Medical Immunology, Sixth Edition, Edited by Gabriel Virella, Chapter-30. AIDS and Other Acquired Immunodeficiency Diseases, pg-436).


DIFFICULTIES IN DEVELOPING AN HIV VACCINE

The most difficult challenges today for HIV vaccine researchers are

•    HIV attacks CD4+ T cells, the most important part of the immune system that coordinates and directs the activities of other types of immune cells that combat intruding microbes.

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For a vaccine to be effective, it will need to be able to activate these cells--a difficult feat if they're being infected and destroyed by the virus.

•    Scientists have not identified the correlates of immunity, or protection, for HIV and are still trying to design vaccines to induce the appropriate immune responses necessary for protection. Unlike other viral diseases for which investigators have made successful vaccines, there are no documented cases of complete recovery from HIV infection. Therefore, HIV vaccine researchers have no human model of recovery from infection and subsequent protection from re-infection to guide them.

•    In an infected person, HIV continually mutates and recombines to evolve into new strains of virus that differ slightly from the original infecting virus. This extensive diversity of HIV poses a challenge to vaccine design as an HIV vaccine would need to protect against many different strains of the virus circulating throughout the world. Conventional vaccines have had to protect against one or a limited number of strains.

•    Ideally, an HIV vaccine will marshal two kinds of immune responses to fight HIV: T cells and antibodies secreted by B cells. These immune responses would prevent the establishment and spread of the virus from the original site of infection and decrease the effects of the disease in those who do become infected. However, scientists have not yet been able to stimulate both types of responses.

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To date, researchers have only stimulated T cell responses weakly with experimental HIV vaccines and have had difficulty stimulating the production of antibodies that protect against a broad range of HIV strains.

•    Researchers lack the knowledge about which HIV immunogens, pieces of HIV used to construct an experimental HIV vaccine, will get the immune system to recognize HIV during an actual encounter and protect against disease.

•    Lack of a practical animal model to predict the effectiveness of an HIV vaccine in people hampers HIV vaccine development. Currently, researchers rely on experiments using non-human primate models infected with the simian cousin of HIV, known as SIV, and an engineered combination of SIV and HIV, known as SHIV, to somewhat mimic disease progression. Evaluating experimental vaccines in these animals requires an SIV or SHIV analog instead of the actual HIV vaccine candidate used in clinical trials in humans. (www.niaid.nih.go)


CONCLUSION

Vaccines teach the immune system to recognize a specific harmful organism and fight off the disease when the body faces the real pathogen. Despite extraordinary advances in understanding both HIV and the human immune system, a fully successful HIV vaccine continues to elude researchers. However, vaccination has contributed significantly towards improving human health as follows:

•        The elimination in 1977 of smallpox as a human disease

•       Currently, it is estimated that vaccination saves the lives of 3 million children a year

•       Eradication, elimination and control of infectious diseases.


REFERENCES

1.     (en.wikipedia.org/wiki/Vaccination).

2.     Medical Immunology, Sixth Edition, Edited by Gabriel Virella, Chapter-30.

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AIDS and Other Acquired Immunodeficiency Diseases, pg-436.

3.     www.niaid.nih.go National Institute of Allergy and Infectious Disease, Challenges in Designing HIV Vaccines, September 10, 2008.

4.     www.immune.org.nz/types-vaccines Immunisation Advisory Center, University of Aukland, 07-10-2011

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