Anthrax protective antigen administered by DNA vaccination to distinct subcellular locations potentiates humoral and cellular immune responses

作者：Midha Shuchi; Bhatnagar Rakesh^*

来源：European Journal of Immunology, 2009, 39(1): 159-177.

DOI：10.1002/eji.200838058

• Anthrax
• DNA vaccination
• Protease-cleaved fragment
• Protective antigen

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 approximate to 10(5) and approximate to 10(3), respectively, provided protection to approximate 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.

• 出版日期2009-1