Vaccination is an important tool for handling healthcare programs both in developed and developing countries. The current global scenario calls for a more-efficacious, acceptable, cost-effective and reliable method of immunization for many fatal diseases. It is hoped that the adoption of oral vaccines will help to provide an effective vaccination strategy, especially in developing countries. Mucosal immunity generated by oral vaccines can serve as a strong first line of defense against most of the pathogens infecting through the mucosal lining. Advances in elucidating the mechanism of action of oral vaccines will facilitate the design of more effective, new generation vaccines. There are promising developments in the use of different agents to effectively deliver the vaccine candidate. It is hoped that ongoing research may be able to set another cardinal point, after polio vaccine, in eradicating infectious diseases.
Based on the hypothesis that immune outcome can be influenced by the form of antigen administered and its ability to access various antigen‐processing pathways, we targeted the 63 kDa fragment of protective antigen (PA) of Bacillus anthracis to various subcellular locations by DNA chimeras bearing a set of signal sequences. These targeting signals, namely, lysosome‐associated membrane protein 1 (LAMP1), tissue plasminogen activator (TPA) and ubiquitin, encoded various forms of PA viz. lysosomal, secreted and cytosolic, respectively. Examination of IgG subclass distribution arising as a result of DNA vaccination indicated a higher IgG1:IgG2a ratio whenever the groups were immunized with chimeras bearing TPA, LAMP1 signals alone or when combined together. Importantly, high end‐point titers of IgG antibodies were maintained until 24 wk. It was paralleled by high avidity toxin neutralizing antibodies (TNA) and effective cellular adaptive immunity in the systemic compartment. Anti‐PA and TNA titers of ≈105 and ≈103, respectively, provided protection to ≈90% of vaccinated animals in the group pTPA‐PA63‐LAMP1. A significant correlation was found between survival percentage and post‐challenge anti‐PA titers and TNA titers. Overall, immune kinetics pointed that differential processing through various compartments gave rise to qualitative differences in the immune response generated by various chimeras.
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