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Tuberculosis (TB) is one of the major devastating diseases in the world, mainly caused by Mycobacterium tuberculosis. Furthermore, multi-drug resistant TB and extremely drug resistant TB are becoming big problems globally. Bacillus Calmette-Guerin (BCG) is the only available vaccine which provides protection against TB. The BCG vaccine is effective in children but not recommended in adults and elderly patients due to an associated low risk of infection with Mycobacterium tuberculosis and variable effectiveness of the vaccine. The main aim of this research study is to develop such a vaccine which will provide a better and safer profile in children and adults, as well as in elderly patients. In this present study, we prepared pulmonary tubercular vaccine by using an Antigen 85 complex (Ag85)-loaded nanocarrier such as the immunostimulating complex (ISCOM). Immunological outcomes clearly indicated significant improvement in humoral as well as cellular immune responses after pulmonary immunization with ISCOMs containing Quil A in mice.

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Adjuvants are compounds that, when combined with an antigen, potentiate an immune response in an immunized species. There are numerous pathogens for which there are no protective vaccines and since alum is the only adjuvant licensed for use in humans, there is a clear need for more effective adjuvant preparations. In this study we describe the immunopotentiating properties of three novel molecular aggregate formulations based on tomatine (RAM1), a glycosylamide lipid (RAM2) and a fifth generation dendrimeric polymer (RAM3) respectively. These formulations were evaluated for their ability to augment antigen-specific antibody responses when administered with a soluble protein antigen. All three adjuvants were shown to be nontoxic to mice and elicited antigen-specific antibody responses. Of the three formulations, RAM1 was found to induce the highest titers of antibody; these were substantially higher than those induced by reference control adjuvants. RAM1 elicited antibodies of the IgG1 and IgG2a subclasses indicating, indirectly, that this adjuvant can stimulate Th2 and Th1 type immunity.

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Aluminum salts are currently the only widely used adjuvant for human vaccines. Over the past 10-15 years, a large research effort has attempted to find novel adjuvants with ability to induce a broad range of immune responses, including cell-mediated immunity. The immunostimulating complex or ISCOM is one adjuvant with multiple adjuvant properties. ISCOMs are open cage-like complexes typically with a diameter of about 40 nm that are built up by cholesterol, lipid, immunogen, and saponins from the bark of the tree Quillaia saponaria Molina. ISCOMs have been demonstrated to promote antibody responses and induce T helper cell as well as cytotoxic T lymphocyte responses in a variety of experimental animal models, and have now progressed to phase I and II human trials. This review describes recent developments in the understanding of the structure, composition, and preparation of ISCOMs and will cover important aspects of the understanding of the adjuvant functions of ISCOMs and how they act on the immune system.

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It is well established that ISCOMs function efficiently as an antigen-presenting system and protective immunity has been evoked against a variety of infectious agents. The built-in saponin adjuvant from Quillaja saponaria Molina is responsible for the strong immunoenhancing activity displayed by the ISCOM. However, to allow the use of ISCOMs in human vaccines it is necessary to determine the immunological properties and toxicity of chemically defined Quillaja components. Thus, the present study was carried out in a mouse model to determine the adjuvant activity and toxicity of "free", isolated Quillaja components, as well as formulated into particles, i.e. ISCOM matrix. The purified Quillaja components and the ISCOM matrix formulations were examined for their adjuvant activity in a model system consisting of purified influenza virus antigen and Quillaja saponins. It was demonstrated that a Quillaja component, designated QH-C, either as a "free" component or in an ISCOM matrix, has a strong adjuvant activity, but little or no toxicity in the doses tested. In addition, QH-C in the form of ISCOM matrix does not induce any local reactions at the site of injection. Thus, ISCOMs containing the QH-C component, devoid of toxicity, but with strong adjuvant activity, can prove to be useful in adjuvant formulations for human use.

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