University of Chicago
Type of paper: Thesis/Dissertation Chapter
A vaccine is a biological preparation intended to improve an individual’s immunity to a specific illness or disease. Most vaccines are composed of weakened or killed forms of an agent that resembles a disease-causing microorganism. A typically safe version of the pathogen, which is unable to cause the disease, is then produced by the altered or inactivated state. Once the vaccine is administered into the blood stream, the agent is recognized as a foreign body, which then triggers the process of active immunity, which in turn builds up antibodies to fight this particular pathogen (Wisegeek).
Vaccination is intended to provide protection so that if the body comes in contact with the same type of disease in the future, the immune system will already have memory antibodies to fight the disease before symptoms occur. Since the introduction of vaccines for illness causing pathogens, diseases such as measles, polio and the common flu have greatly decreased in occurrence. With that being said, not all vaccines have been proven to be safe or effective. One virus that does not yet have an effective preventative vaccine is the Human Immunodeficiency Virus (HIV). HIV is a retrovirus that attacks the human immune system.
Transmission of the virus can occur in many different ways; through contact of infected secretions of one person with the genital, oral, or rectal mucous membranes of another person. HIV can also be transmitted through blood and from mother to child during pregnancy, childbirth or through breast milk (Healthmagic, 2010). The virus is characterized by its two glycoproteins: gp120 and gp41. The larger of the two glycoroteins is gp120, this molecule is the primary site of attachment to CD4 receptors of the host cell and while also triggering inflammation when shed into the blood.
Gp41 promotes fusion to a target cell while remaining on the cytoplasmic membrane. HIV infects four types of cells: helper T cells, macrophages, smooth muscle cells and dendritic cells. Attachment and entry of HIV into T cells and macrophages occurs in three steps. In the first step, gp120 binds to the CD4 (cluster of differentiation 4) molecules on a host cell; forming a complex known as gp120-CD4 complex. Second, this complex binds to a chemokine receptor, which removes gp120 from the virion. This process if finalized when the virion binds to a cell.
Once bound to a cell, the virion’s envelope contacts and fuses with the cytoplasmic reticulum through the medium of the gp41. The HIV capsid then gets insinuated into the cytoplasm; however its covering of gp41 gets left behind and becomes part of the cells cytoplasmic membrane. With gp41 remaining on the cytoplasmic membrane, it is then able to fuse with over 500 cells to form a syncytium, which is a giant cell with multiple nuclei. This fusion is very dangerous because it allows HIV to move from cell to cell without being exposed to any antibodies that are in the blood.
During synthesis, an enzyme called reverse transcriptase, transcribes the double stranded DNA using TRNA as a primer in the cytoplasm. Reverse transcriptase is prone to making a lot of errors during this process which generates an abundance of new antigenic variations of HIV. The double stranded DNA then enters the nucleus and is inserted into a chromosome by the enzyme integrase. Once the double stranded DNA is integrated into the cellular DNA it remains a part of it for life. Once the newly infected double stranded DNA is integrated into the chromosome, it cannot be changed or counter acted.
However, there are various therapeutic vaccines to help regulate the virus (Bauman, 2011). Therapeutic vaccines are designed to help treat people who are HIV positive by controlling the virus. Those who are infected with HIV and live with it for an extended period of time, start to develop antibodies on a specific part of the glycoprotein 120, which is in charge of initiating the activation of HIV. This antibody, C5, is known to be crucial in producing certain antibodies that are able to control HIV by regulating its hyper action that destroys the human immune system.
However, induction of these antibodies cannot occur unless GP120 is at the surface of the virus. In order for gp120 to be at the surface of the virus, gp41 and the antibody C5 must fuse. This is a process that is unable to occur on its own (Bionor Pharma, 2010). The therapeutic vaccine Vacc-C5, invented by Bionor Immuno, is an antibody-mediated vaccine that binds C5 and gp41 together so that the antibodies from C5 can be effective and help regulate the virus.
A preventative vaccine is designed to prevent individuals from getting HIV. Over the recent years there have been many studies and attempts to create an effective vaccine to prevent HIV but unfortunately none have been proven to be successful. A good example of a preventative vaccine, that had hopeful prospects, is the AIDSVAX vaccine developed by Philip Berman. AIDSVAX is composed of a synthetic version of the glycoprotein 120, a part of the HIV’s envelope, which the virus uses as a mechanism to latch onto and enter the cell.
This version of gp120 was meant to stimulate the production of antibodies against strains of HIV that it resembles, giving immunity to the strain of HIV. However, this vaccine was proven ineffective after the clinical trials. Near the part of the gp120 that attaches to the cell, there is a chain of a specific sequence of amino acids called the V3loop. The V3loop is the most variable part of the glycoprotein and in order for an envelope vaccine to produce an antibody response; it has to be against the exact strain of the virus (Brian Deer).
HIV is a virus that has many different strains and is also constantly going under mutations within replication therefore preventing the AIDSVAX vaccine from halting the infection of the virus. The development of vaccines against HIV has not yet reached a point of success. HIV is a virus that has many characteristics that make it highly difficult to prevent and treat. HIV is capable surpassing immune response because of its ability of generating many antigenic variants; due to it being so highly mutable.
Also, not only does HIV attack the various cells in the body that combat infections in the immune system but it can also spread through syncytia via formation by gp41, evading detection from immune defence all together. Vaccine development is still an important tool in healthcare because there are still millions of people who currently live with the disease and many who are at a high risk of contracting it. However, even with the many developments in medical research, the production of vaccines is still a costly procedure which also presents ethical and medical problems.
In the meantime, the spread of infection must be slowed through the increase of awareness and availability, of information on the risks of contracting the disease. In order to avoid contraction, Health Care Providers must provide the public with information about safer practices, such as; safe sex and the proper use of sterile needles and syringes for injections. They can also promote proper blood screening procedures and spread information on medications, therapeutic vaccines and other ways an individual who already has HIV can prevent the spread of the virus as well.