Administration of Antibody to the Lung Protects Mice against Pneumonic Plague

Abstract

Intratracheal delivery of aerosolized monoclonal antibodies with specificity for Yersinia pestis LcrV and F1 antigens protected mice in a model of pneumonic plague. These data support the utility of inhaled antibodies as a fast-acting postexposure treatment for plague.

Yersinia pestisCan Bypass Protective Antibodies to LcrV and Activation with Gamma Interferon To Survive and Induce Apoptosis in Murine Macrophages

“…The opsonization of Y. pestis with anti-LcrV IgG1 MAb 7.3 (17) increases phagocytosis and decreases apoptosis in naïve J774A.1 cells (43). In addition, MAb 7.3 is known to provide protection against fully virulent Y. pestis in murine bubonic and pneumonic plague infections (15)(16)(17). We opsonized KIM5/GFP or KIM5 with MAb 7.3 and repeated the phagocytosis, intracellular survival, and LDH release assays.…”

Adenovirus-Mediated Delivery of an Anti-V Antigen Monoclonal Antibody Protects Mice against a Lethal Yersinia pestis Challenge

“…When anti-F1 and anti-V antigen MAbs are coadministered to mice, a synergistic effect is observed in response to Y. pestis challenge (20,21).…”

“…The live attenuated vaccines are all based on mutants of fully virulent strains, but they are not licensed for use in the United States, relating to significant safety and efficacy concerns (21,24,43; http://cdc.gov/ncidod/dvbid/plague/prevent .htm). A formaldehyde-killed vaccine has been developed, but this vaccine is also no longer licensed or available for use in the United States, relating to adverse side effects and the inability to provide complete protection against pneumonic plague (21,43). Current vaccine development efforts are focused largely on recombinant Y. pestis proteins, with V antigen and the capsular F1 protein as the primary targets.…”

“…Transfer of immune sera from animals immunized with V antigen to naive animals confers immediate protection against Y. pestis challenge (16,33). Additionally, passive transfer of an anti-V antigen monoclonal antibody (MAb) protects mice against a lethal challenge with Y. pestis (20)(21)(22). Delivery of the coding sequences for MAbs with viral vectors has been effective against both infectious diseases and cancers and is an alternative platform to administration of purified antibodies (9,10,25,26,28,45,50).…”

Anticorps et bioterrorisme

“…Nous avons également obtenu un fragment d'Ac recombinant dirigé contre la seconde sous-unité de cette même toxine, le facteur létal [12], comme cela avait été préconisé par les experts du charbon [13]. La mélioïdose [14], et surtout la peste [15], sont des maladies bactériennes incluses dans le RBP que des Ac peuvent aider à contrôler. Le virus de la variole peut être neutralisé par des Ac dirigés contre les protéines de surface B5 [16] ou L1 [17].…”