How Vaccines work
The immune system is a complex system of interacting cells whose primary purpose is to identify foreign substances, such as microorganisms and cancer cells, and to develop a defense, or immune response, against them. The immune response can be sub-divided into non-specific or innate immunity and specific or acquired immunity.
Innate immunity is present at all times in healthy individuals and consists of a series of mechanical and chemical barriers to prevent harmful substances from entering the body and from specialized chemicals and cells to destroy foreign substances within the body. These non-specific mechanisms provide the first line of defense against disease-causing microorganisms until a specific immune response can develop.
Specific immunity only develops after the first exposure to a foreign substance and it takes days to weeks to fully mature. On subsequent contact with the same substance, the previously acquired immunity enables the body to specifically recognize or "remember" a particular substance or agent and to make a more rapid and stronger immune response to it. Immunologic memory is often long-lived and may give life-long protection to re-infection with infectious agents. The specific immune system can be stimulated to produce antibody and cellular immunity either by exposure to the natural disease or by administration of a vaccine.
The immunity mediated by soluble proteins, such as antibody and complement, found in the blood and secretions is referred to as "humoral immunity". Antibodies belong to a family of protein molecules known as immuneglobulins that can specifically recognize foreign substances or antigens. Attachment of antibody to antigens on an infecting microorganism marks the cell or virus particle as foreign and enables the immune system to destroy or neutralize the invader. Foreign particles coated with antibody are said to be opsonized or "prepared for eating" and can be more readily identified, ingested and killed by specialized cells called phagocytes. This effect can be strengthened if other components of the humoral immune system, called complement, bind to the antibody attached to antigen. The binding of complement to the surface of microbial cells can also directly cause cell death and cell disruption, in the absence of phagocytic cells, by punching holes in the cell membrane. Although this process can occur in a limited form without antibody, as part of the innate immune system, the presence of bound antibody further enhances the process. The attachment of antibody to microorganisms can also block infection by preventing the interaction of microorganisms, or their products, with host cells. This process can hinder the colonization of mucosal surfaces by microbes, prevent infectious agents from invading body cells and neutralize bacterial toxins before they can poison the host.
Cellular immunity is effected by white blood cells known as lymphocytes of which there are two major classes, B and T lymphocytes. B cells are key players in the development of humoral immunity. The B cells have specific immuneglobulin antigen binding receptors on their cell surface through which they can bind antigen. This event, together with co-stimulatory signals provided by antigen presenting cells and T cells, activates the B cells, which increase in number before developing into plasma cells or memory cells. Plasma cells secrete antibody specific for the antigen initially recognized by the B cell.
Memory cells enable the body to make a more rapid antibody response on re-encountering the antigen. T cells are involved in many ways in the development and regulation of immune responses. One subset of T cells, called T helper cells, assists in the development of the humoral immune response through interactions with B cells. Another subset of T cells, cytotoxic T cells, are able to specifically identify and kill cells infected with intracellular bacteria or viruses and cancer cells. T cells are also involved in inducing inflammation and in inhibiting certain immune responses.
Vaccines interact with the immune system to produce a specific immune response, which is often identical to that produced by the natural infection but without the hazards associated with the disease. The widespread use of vaccines has led to marked reductions in the incidence of numerous infectious diseases, the near elimination of polio and the eradication of smallpox. Vaccines prevent illness or death for millions of individuals every year and vaccination is undoubtably one of the greatest success stories in the history of medicine.
Vaccines can be made from inactivated whole microorganisms. Vaccines of this type include Baxter's tick-borne encephalitis, influenza, hepatitis A and Ross River vaccines. However, effective protective immunity can also be generated by immunizing with one or more antigens, purified from the disease causing agent or produced using recombinant DNA technology. One potential advantage of "subunit vaccines" is that unwanted components can be excluded to improve product safety. Baxter's candidate vaccines to protect against Lyme borreliosis and E. coli urinary tract infections are subunit vaccines using protein antigens. Other bacterial vaccines use polysaccharide antigens, since some disease causing bacteria produce a polysaccharide capsule that enables the bacteria to avoid recognition by the immune system. Coating of the capsule with antibodies greatly enhances the immune system's ability to kill these organisms. Unfortunately, many polysaccharide antigens either fail to stimulate the immune system sufficiently to produce protective antibodies, or the antibody response is short-lived. These defects can be overcome by linking or conjugating the polysaccharide to a carrier protein. Baxter Vaccine is currently developing a number of vaccines using this technology, often using novel immunopotentiating carrier proteins, including vaccines against Neisseria meningitidis (group B, C, Y, W), Streptococcal infections (group A and B Streptococci and Pneumococcus) and Haemophilus influenzae.
Although vaccines are primarily used to provide long-lived immunity that prevents disease, they may also be used to treat pre-existing disease. One of the exciting possibilities in this area is the development of vaccines to treat cancer. Baxter's glycoconjugate vaccine technology can help produce an immune response to non-immunogenic tumour specific carbohydrate antigens. Complementary to this approach, is the use of a live attenuated vaccinia virus delivery system to present protein, tumor-associated antigens to the immune system in such a way that they trigger an immune response. These combined strategies offer the promise of new treatments for certain cancers.