title: Anthrax protective antigen administered by DNA vaccination to distinct subcellular locations potentiates humoral and cellular immune responses.
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 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.
authors.affiliation: School of Biotechnology, Jawaharlal Nehru University, New Delhi, India.
authors.forename: Shuchi
authors.initials: S
authors.lastname: Midha
authors.forename: Rakesh
authors.initials: R
authors.lastname: Bhatnagar
mesh_terms: D000818:Animals; D000881:Anthrax / Q000517:prevention & control*; D022122:Anthrax Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D019470:Biolistics; D016207:Cytokines / Q000276:immunology; D005260:Female; D051907:Lysosomal Membrane Proteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D010959:Tissue Plasminogen Activator / Q000235:genetics / Q000276:immunology; D025801:Ubiquitin / Q000235:genetics / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D016207:Cytokines; D051907:Lysosomal Membrane Proteins; D010959:Tissue Plasminogen Activator; D025801:Ubiquitin; D019444:Vaccines, DNA; C052255:Lamp1 protein, mouse; D052118:Lysosomal-Associated Membrane Protein 1; C030325:anthrax toxin