title: Preserved antiviral adaptive immunity following polyclonal antibody immunotherapy for severe murine influenza infection.
abstract: Passive immunotherapy may have particular benefits for the treatment of severe influenza infection in at-risk populations, however little is known of the impact of passive immunotherapy on the formation of memory responses to the virus. Ideally, passive immunotherapy should attenuate the severity of infection while still allowing the formation of adaptive responses to confer protection from future exposure. In this study, we sought to determine if administration of influenza-specific ovine polyclonal antibodies could inhibit adaptive immune responses in a murine model of lethal influenza infection. Ovine polyclonal antibodies generated against recombinant PR8 (H1N1) hemagglutinin exhibited potent prophylactic capacity and reduced lethality in an established influenza infection, particularly when administered intranasally. Surviving mice were also protected against reinfection and generated normal antibody and cytotoxic T lymphocyte responses to the virus. The longevity of ovine polyclonal antibodies was explored with a half-life of over two weeks following a single antibody administration. These findings support the development of an ovine passive polyclonal antibody therapy for treatment of severe influenza infection which does not affect the formation of subsequent acquired immunity to the virus.
authors.affiliation: Experimental Therapeutics Laboratory, Hanson Institute, and Sansom Institute, School of Pharmacy and Medical Science, University of South Australia, Adelaide, SA, Australia.
authors.forename: Natalie E
authors.initials: NE
authors.lastname: Stevens
authors.affiliation: Experimental Therapeutics Laboratory, Hanson Institute, and Sansom Institute, School of Pharmacy and Medical Science, University of South Australia, Adelaide, SA, Australia.
authors.forename: Antoinette
authors.initials: A
authors.lastname: Hatjopolous
authors.affiliation: Preclinical, Imaging and Research Laboratories, South Australian Health and Medical Research Institute, Gilles Plains, Adelaide, SA, Australia.
authors.forename: Cara K
authors.initials: CK
authors.lastname: Fraser
authors.affiliation: Vaccine Research Group, Department of Molecular and Cellular Biology, School of Biological Sciences, The University of Adelaide, Adelaide, SA, Australia.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Alsharifi
authors.affiliation: Experimental Therapeutics Laboratory, Hanson Institute, and Sansom Institute, School of Pharmacy and Medical Science, University of South Australia, Adelaide, SA, Australia.|Robinson Research Institute, Discipline of Obstetrics and Gynaecology, School of Medicine, The University of Adelaide, Adelaide, SA, Australia.
authors.forename: Kerrilyn R
authors.initials: KR
authors.lastname: Diener
authors.affiliation: Experimental Therapeutics Laboratory, Hanson Institute, and Sansom Institute, School of Pharmacy and Medical Science, University of South Australia, Adelaide, SA, Australia.|Robinson Research Institute, Discipline of Obstetrics and Gynaecology, School of Medicine, The University of Adelaide, Adelaide, SA, Australia.
authors.forename: John D
authors.initials: JD
authors.lastname: Hayball
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D003429:Cross Reactions / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007167:Immunotherapy; D053118:Influenza A Virus, H1N1 Subtype / Q000502:physiology*; D007700:Kinetics; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy* / Q000821:virology; D012756:Sheep
chemical_list: D000914:Antibodies, Viral