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

European Journal of Immunology
Shuchi Midha, Rakesh Bhatnagar

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 approximately 10(5) and approximately 10(3), respectively, provided protection to approximately 90% of vaccinated animals in the group pTPA-PA63-LAMP1. A significant correlation was found between survival percentage and post-challenge ...Continue Reading

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Citations

Sep 18, 2012·Journal of Biotechnology·Lei LiNikolai Petrovsky
Oct 20, 2009·Vaccine·Arthur M Friedlander, Stephen F Little
Sep 5, 2009·Molecular Aspects of Medicine·Robert J CybulskiAlison D O'Brien
Dec 1, 2009·Expert Review of Vaccines·Lesley C Dupuy, Connie S Schmaljohn
Aug 30, 2013·Expert Review of Vaccines·Manpreet KaurRakesh Bhatnagar
Jul 13, 2019·Expert Review of Vaccines·Olga A KondakovaOlga V Karpova
Jul 31, 2020·Expert Opinion on Biological Therapy·Manish ManishRakesh Bhatnagar

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