Select human anthrax protective antigen epitope-specific antibodies provide protection from lethal toxin challenge.
Bacillus anthracis remains a serious bioterrorism concern, and the currently licensed vaccine remains an incomplete solution for population protection from inhalation anthrax and has been associated with concerns regarding efficacy and safety. Thus, understanding how to generate long-lasting protective immunity with reduced immunizations or provide protection through postexposure immunotherapeutics are long-sought goals. Through evaluation of a large military cohort, we characterized the levels of antibodies against protective antigen and found that over half of anthrax vaccinees had low serum levels of in vitro toxin neutralization capacity. Using solid-phase epitope mapping and confirmatory assays, we identified several neutralization-associated humoral epitopes and demonstrated that select antipeptide responses mediated protection in vitro. Finally, passively transferred antibodies specific for select epitopes provided protection in an in vivo lethal toxin mouse model. Identification of these antigenic regions has important implications for vaccine design and the development of directed immunotherapeutics.
Crowe
Sherry R
SR
Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Ash
Linda L
LL
Engler
Renata J M
RJ
Ballard
Jimmy D
JD
Harley
John B
JB
Farris
A Darise
AD
James
Judith A
JA
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000881:Anthrax / Q000453:epidemiology / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000097:blood / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D000942:Antigens, Bacterial / Q000633:toxicity; D001408:Bacillus anthracis / Q000276:immunology*; D001427:Bacterial Toxins / Q000633:toxicity; D023482:Bioterrorism; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D007114:Immunization / Q000379:methods; D007074:Immunoglobulin G / Q000097:blood; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009825:Oklahoma; D010455:Peptides / Q000032:analysis / Q000737:chemistry; D044469:Racial Groups; D014611:Vaccination / Q000379:methods
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D000939:Epitopes; D007074:Immunoglobulin G; D010455:Peptides; C030325:anthrax toxin