Immune response immunogens

Immunogenicity The ability of an immunogen to elicit an immune response. Immunogenicity depends upon foreignness to the host, the size of the immunogen, the complexity of its molecular structure, the length of time it remains in the host and its ability to reach certain immunocompetent cells in order to generate immunity. 

Four-week toxicology studies in rodent and nonrodent The four-week studies are designed for subchronic exposure of rodents and nonrodents to the test article. These studies also look at reversibility of any toxicity observed. Many times these are the pivotal studies used to support the first in human dosing. Toxicokinetic assessments are generally included in repeat-dose toxicity studies. When testing biopharmaceuticals, studies also include assessment and characterization of immune response (immunogenicity). 

The active immunotherapeutic approach is specific and based on the premise that tumor antigens are immunogenic and the host is sufficientiy immunocompetent to mount an effective immune response to an autologous tumor. Theoretically, a weak or suppressed host immune system that had allowed the formation of a tumor may be overridden by active immunization or immunostimulation. In practice, vaccines composed of so-called autologous tumor extracts have been used to treat patients with malignant melanoma (73), and purified melanoma tumor-associated antigens have been used to ehcit antibody responses in melanoma patients (74). 

The first inactivated poliovirus vaccine was introduced in the 1950s in an injectable formulation, and replaced in the 1960s by a live oral poliovirus vaccine. The oral poliovirus vaccine not only elicits systemic immunogenicity but also a localized immune response in the intestinal tract. Unfortunately, the oral poliovirus vaccine has the risk of vaccine-associated paralytic poliomyelitis occurring in approximately 1 case of every 2.4 million doses distributed. The risk with the first dose of oral poliovirus vaccine is 1 case in 750,000 doses.11... 

Many factors have to be considered when developing combination vaccines. First the selected components need to be given on a similar schedule and all components should already be licensed in the United States. The excipients contained in the individual vaccines may interfere with another component when combined, altering a component s immunogenicity. Finally, the immunogenicity of the combination must be similar (within 10%) to the immune response when the components are administered separately. This has been problematic with combinations containing Haemophilus influenza type b vaccine, for which the immune response has been significantly blunted in some combinations.13... 

Immunogenicity The property that gives a substance the ability to provoke an immune response. 

Synthetic haptens mimicking some critical epitopic structures on larger macromolecules are often conjugated to carriers to create an immune response to the larger parent molecule. For instance, short peptide segments can be synthesized from the known sequence of a viral coat protein and coupled to a carrier to induce immunogenicity toward the native virus. This type of synthetic approach to immunogen production has become the basis of much of the current research into the creation of vaccines. 

Some synthetic carriers actually are designed to have low immunogenicity on their own to minimize the potential for antibody production against them. When a hapten is coupled to these molecules, the immune response is directed principally toward the modification, not at the carrier. This design approach guides most of the immune response toward the desired target and minimizes the production of carrier-specific antibodies. 

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