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CMP as an adjuvant in nasal vaccines
Many pathogens cause disease by first colonizing and then penetrating the mucosal barrier of the gut, genital or respiratory tracts. In response to this threat the nasal mucosa, like other mucosal surfaces of the body, has evolved a sophisticated immune barrier to protect against the threat of infection. The mucosal surfaces including the nasal mucosa contain a particularly high concentration of immune surveillance cells including dendritic cells, regarded as the professional antigen presenting cells of the immune system, macrophages and M cells.
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| The primary advantages for choosing the nose as the route for immunization has includes the following: |
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The nose is easily accessible for vaccine delivery |
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The nasal passages are highly vascularized and the presence of |
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microvilli create a very large effective surface area |
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Both mucosal and systemic immune responses are induced |
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The nasal mucosa is part of the common mucosal immune system |
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allowing rapid trafficking of effector immune cells to distal sites |
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Nasal application avoids injections which requires costly medical |
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supervision as well as presenting a risk of infection |
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Nasal delivery is less expensive and suited to mass vaccination |
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strategies. This is of particular relevance to developing countries |
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However, to achieve a good immunological response leading to adequate protective neutralizing antibodies it is necessary to overcome the natural immune tolerance of the nasal mucosa by the inclusion of a Th1 enhancing adjuvant. Hasegawa and Strong demonstrated this approach with a nasal flu vaccine containing the chitin microparticles (J.Med.Virology, 2005). Also Hamajima and Strong demonstrated efficacy in a nasal HIV DNA vaccine (Viral Immunol., 2003). A further usefulness for CMP is in enhancing the efficacy of other adjuvants in vaccine formulations through adjuvant synergy as shown by Asahi-Ozaki and Strong in the most recent publication (Microbes and Infection, 2006).
One of the most interesting advantages of nasal immunization is the induction of IgA. This antibody is secreted into mucosal fluids and is of particular importance in the early phase of neutralizing infections. Unlike IgG, which is highly antigen specific, IgA has a much broader specificity and is able for example to cross-react with different influenza strains
Given the effectiveness of CMP as a nasal mucosal adjuvant, it would be possible to develop numerous products after further research and development. Nasal vaccination is gaining great popularity because of the possibility of mass application with minimal clinical supervision. Also, since the respiratory tract is the main portal of entry for many infectious diseases, establishing a robust immune response in the nasal mucosa offers greater protection. This is of particular relevance for HIV and FLU vaccine development.
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Scientific papers
Protection against influenza virus infection by intranasal administration of hemagglutinin vaccine with chitin microparticles as an adjuvant.
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Chitin microparticles (CMP): A useful adjuvant for inducing viral specific immunity when delivered intranasally with an HIV-DNA vaccine.
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Intranasal administration of adjuvant-combined recombinant influenza virus HA vaccine protects mice from the lethal H5N1 virus infection.
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