title: Complement inhibition enables tumor delivery of LCMV glycoprotein pseudotyped viruses in the presence of antiviral antibodies.
abstract: The systemic delivery of therapeutic viruses, such as oncolytic viruses or vaccines, is limited by the generation of neutralizing antibodies. While pseudotyping of rhabdoviruses with the lymphocytic choriomeningitis virus glycoprotein has previously allowed for multiple rounds of delivery in mice, this strategy has not translated to other animal models. For the first time, we provide experimental evidence that antibodies generated against the lymphocytic choriomeningitis virus glycoprotein mediate robust complement-dependent viral neutralization via activation of the classical pathway. We show that this phenotype can be capitalized upon to deliver maraba virus pseudotyped with the lymphocytic choriomeningitis virus glycoprotein in a Fischer rat model in the face of neutralizing antibody through the use of complement modulators. This finding changes the understanding of the humoral immune response to arenaviruses, and also describes methodology to deliver viral vectors to their therapeutic sites of action without the interference of neutralizing antibody.
authors.affiliation: Center for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Laura
authors.initials: L
authors.lastname: Evgin
authors.affiliation: Center for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute , Ottawa, Ontario, Canada.
authors.forename: Carolina S
authors.initials: CS
authors.lastname: Ilkow
authors.affiliation: Center for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Bourgeois-Daigneault
authors.affiliation: Center for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute , Ottawa, Ontario, Canada.
authors.forename: Christiano Tanese
authors.initials: CT
authors.lastname: de Souza
authors.affiliation: Center for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute , Ottawa, Ontario, Canada.
authors.forename: Lawton
authors.initials: L
authors.lastname: Stubbert
authors.affiliation: Center for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute , Ottawa, Ontario, Canada.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Huh
authors.affiliation: Center for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute , Ottawa, Ontario, Canada.
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Jennings
authors.affiliation: Center for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Monique
authors.initials: M
authors.lastname: Marguerie
authors.affiliation: Toronto General Research Institute, University Health Network , Toronto, Ontario, Canada.
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Acuna
authors.affiliation: Center for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Keller
authors.affiliation: Children's Hospital of Eastern Ontario Research Institute , Ottawa, Ontario, Canada.
authors.forename: Charles
authors.initials: C
authors.lastname: Lefebvre
authors.affiliation: Center for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute , Ottawa, Ontario, Canada.
authors.forename: Theresa
authors.initials: T
authors.lastname: Falls
authors.affiliation: Center for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute , Ottawa, Ontario, Canada.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Le Boeuf
authors.affiliation: Center for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute , Ottawa, Ontario, Canada.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Auer
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania , Philadelphia, Pennsylvania, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Lambris
authors.affiliation: Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada; Department of Surgery, Mount Sinai Hospital and University of Toronto, Toronto, Ontario, Canada.
authors.forename: J Andrea
authors.initials: JA
authors.lastname: McCart
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada; Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
authors.forename: David F
authors.initials: DF
authors.lastname: Stojdl
authors.affiliation: Center for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: John C
authors.initials: JC
authors.lastname: Bell