Abstract
An intense effort has been launched to develop improved anthrax vaccines that confer rapid, long lasting protection preferably with an extended stability profile amenable for stockpiling. Protective antigen (PA)-based vaccines are most favored as immune responses directed against PA are singularly protective, although the actual protective mechanism remains to be unraveled. Herein we show that contrary to the prevailing view, an efficacious PA-based vaccine confers protection against inhalation anthrax by preventing the establishment of a toxin-releasing systemic infection. Equally importantly, antibodies measured by the in vitro lethal toxin neutralization activity assay (TNA) that is considered as a reliable correlate of protection, especially for PA protein-based vaccines adjuvanted with aluminum salts appear to be not absolutely essential for this protective immune response.
Conflict-of-interest statement
The authors declare no competing financial interests.
Author contributions
TJM, P-YP, TH, TWA and LPP designed research and analyzed data. AV assisted with TNA, GML assisted with mouse studies, HY provided novel reagents. LPP supervised the study and wrote the paper.
Acknowledgments
This work was in part supported by the Intramural Research Program of the National Cancer Institute, Center for Cancer Research, NIH and by a 3-y competitive research funding award to L.P.P from the Trans-NIH/FDA Intramural Biodefense Program. We gratefully acknowledge the receipt of reagents from the Biodefense and Emerging Infections Research Resources Repository (BEI Resources, NIAID) for this study. We also express our gratitude to Drs Anne Boyer and John Barr at the CDC for assistance with LF measurements in the rabbit sera.