title: Recombinant rabies virus particles presenting botulinum neurotoxin antigens elicit a protective humoral response in vivo.
abstract: Botulinum neurotoxins are one of the most potent toxins found in nature, with broad medical applications from cosmetics to the treatment of various neuropathies. Additionally, these toxins are classified as Category A-Tier 1 agents, with human lethal doses calculated at as little as 90 ng depending upon the route of administration. Of the eight distinct botulinum neurotoxin serotypes, the most common causes of human illness are from serotypes /A, /B, and /E. Protection can be achieved by eliciting antibody responses against the receptor-binding domain of the neurotoxin. Our previous research has shown that recombinant rabies virus-based particles can effectively present heterologous antigens. Here, we describe a novel strategy using recombinant rabies virus particles that elicits a durable humoral immune response against the botulinum neurotoxin receptor binding domains from serotypes /A, /B, and /E. Following intramuscular administration of β-propiolactone-inactivated rabies virus particles, mice elicited specific immune responses against the cognate antigen. Administration of a combination of these vectors also demonstrated antibody responses against all three serotypes based on enzyme-linked immunosorbent assay (ELISA) measurements, with minimal decay within the study timeline. Complete protection was achieved against toxin challenge from the serotypes /A and /B and partial protection for /E, indicating that a multivalent approach is feasible.
authors.affiliation: Molecular Targeting Technologies, Inc. , West Chester, Pennsylvania, USA ; Department of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University , Philadelphia, Pennsylvania, USA.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Hudacek
authors.affiliation: Inventox, Inc., Lankenau Institute for Medical Research , Wynnewood, Pennsylvania, USA.
authors.forename: Fetweh H
authors.initials: FH
authors.lastname: Al-Saleem
authors.affiliation: Department of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University , Philadelphia, Pennsylvania, USA.
authors.forename: Mallory
authors.initials: M
authors.lastname: Willet
authors.affiliation: Department of Biochemistry, Sidney Kimmel Medical College, Thomas Jefferson University , Philadelphia, Pennsylvania, USA.
authors.forename: Travis
authors.initials: T
authors.lastname: Eisemann
authors.affiliation: Molecular Targeting Technologies, Inc. , West Chester, Pennsylvania, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Mattis
authors.affiliation: Inventox, Inc., Lankenau Institute for Medical Research , Wynnewood, Pennsylvania, USA.
authors.forename: Lance L
authors.initials: LL
authors.lastname: Simpson
authors.affiliation: Department of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University , Philadelphia, Pennsylvania, USA ; Department of Biochemistry, Sidney Kimmel Medical College, Thomas Jefferson University , Philadelphia, Pennsylvania, USA ; Jefferson Vaccine Center, Thomas Jefferson University , Philadelphia, Pennsylvania, USA.
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Schnell