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Mucosal Vaccination Against Airborne Pathogens Using Antigen-loaded Microparticles

Menon MD, Gautam M, Gairola S, Bannalikar AS, Jain RR, Mehta MR.

RDD Asia 2016. Volume , 2016: 81-100.

Abstract:

The emergence of new and multi-antibiotic resistant pathogens have proven to be serious challenges for chemotherapy of infectious diseases. This has stimulated vaccine research and development in general, with mucosal vaccination emerging as an effective alternative to parenterally delivered vaccines. Mucosal immunization via the nasal or pulmonary route offers several potential advantages for treating respiratory pathogens – stemming from mimicking the site of natural infection using a needle-free approach. While perhaps not a concern in developed countries, the possibility of creating stable formulations which do not require cold chain distribution offers tremendous advantages to mass immunization programs in emerging economies.

Mucosal immunity (mediated via IgA) is the first line of defense against pathogens and precedes the emergence of serum immunity (IgG). Immunizing against invading microbes at a mucosal surface results in antibody titers in local secretions which correlate more strongly with disease prevention than do serum antibody levels. To enhance the immunogenicity of M cells (a type of antigen presenting cell) and ensure effective targeting, novel strategies in vaccine development include the use of mucoadhesive polymers and particulate delivery systems. These approaches are intended to stabilize and protect antigens and increase their residence time through controlled/ slow release to mimic in a single administration the classical booster immunization approach. In this investigation, we report on nasal and lung mucosal vaccine delivery systems for treatment of Klebsiella pneumonia (KP) and Haemophilus influenzae type b (Hib). Antibody responses (IgG and IgA titers measured by ELISA) and disease prevention following pathogen injection after nasal and lung mucosal antigen delivery were compared to parenteral antigen delivery in Wistar rats. 

The investigation suggested that an appropriate antigen powder delivered to mucosal nasal and lung surfaces provided higher antibody titers and conferred protection against the respective KP and Hib pathogens, making this approach a promising alternative to conventional injections. Some histological indicators of toxicity were observed and require further elucidation.