Antigenic sites on the HN domain of botulinum neurotoxin A stimulate protective antibody responses against active toxin

Sci Rep. 2015 Oct 28:5:15776. doi: 10.1038/srep15776.


Botulinum neurotoxins (BoNTs) are the most toxic substances known. BoNT intoxicates cells in a highly programmed fashion initiated by binding to the cell surface, internalization and enzymatic cleavage of substrate, thus, inhibiting synaptic exocytosis. Over the past two decades, immunological significance of BoNT/A C-terminal heavy chain (HC) and light chain (LC) domains were investigated extensively leading to important findings. In the current work, we explored the significance of BoNT/A heavy chain N-terminal (HN) region as a vaccine candidate. Mice were immunized with recombinant HN519-845 generating antibodies (Abs) that were found to be protective against lethal dose of BoNT/A. Immuno-dominant regions of HN519-845 were identified and individually investigated for antibody response along with synthetic peptides within those regions, using in vivo protection assays against BoNT/A. Results were confirmed by patch-clamp analysis where anti-HN antibodies were studied for the ability to block toxin-induced channel formation. This data strongly indicated that HN519-593 is an important region in generating protective antibodies and should be valuable in a vaccine design. These results are the first to describe and dissect the protective activity of the BoNT/A HN domain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence / physiology
  • Animals
  • Antibodies, Bacterial / immunology*
  • Antibody Formation / immunology*
  • Botulinum Toxins, Type A / immunology*
  • Immunization / methods
  • Mice
  • Neurotoxins / immunology*
  • Peptide Fragments / immunology
  • Peptides / immunology
  • Protein Binding / immunology
  • Toxins, Biological / immunology*
  • Vaccination / methods


  • Antibodies, Bacterial
  • Neurotoxins
  • Peptide Fragments
  • Peptides
  • Toxins, Biological
  • Botulinum Toxins, Type A