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

Midha, Shuchi ; Bhatnagar, Rakesh (2009) Anthrax protective antigen administered by DNA vaccination to distinct subcellular locations potentiates humoral and cellular immune responses European Journal of Immunology, 39 (1). pp. 159-177. ISSN 0014-2980

Full text not available from this repository.

Official URL: http://onlinelibrary.wiley.com/doi/10.1002/eji.200...

Related URL: http://dx.doi.org/10.1002/eji.200838058

Abstract

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.

Item Type:Article
Source:Copyright of this article belongs to John Wiley and Sons.
Keywords:Anthrax; DNA Vaccination; Protease-cleaved Fragment; Protective Antigen
ID Code:63332
Deposited On:28 Sep 2011 10:30
Last Modified:28 Sep 2011 10:30

Repository Staff Only: item control page