title: Brunenders: a partially attenuated historic poliovirus type I vaccine strain.
abstract: Brunenders, a type I poliovirus (PV) strain, was developed in 1952 by J. F. Enders and colleagues through serial in vitro passaging of the parental Brunhilde strain, and was reported to display partial neuroattenuation in monkeys. This phenotype of attenuation encouraged two vaccine manufacturers to adopt Brunenders as the type I component for their inactivated poliovirus vaccines (IPVs) in the 1950s, although today no licensed IPV vaccine contains Brunenders. Here we confirmed, in a transgenic mouse model, the report of Enders on the reduced neurovirulence of Brunenders. Although dramatically neuroattenuated relative to WT PV strains, Brunenders remains more virulent than the attenuated oral vaccine strain, Sabin 1. Importantly, the neuroattenuation of Brunenders does not affect in vitro growth kinetics and in vitro antigenicity, which were similar to those of Mahoney, the conventional type I IPV vaccine strain. We showed, by full nucleotide sequencing, that Brunhilde and Brunenders differ at 31 nucleotides, eight of which lead to amino acid changes, all located in the capsid. Upon exchanging the Brunenders capsid sequence with that of the Mahoney capsid, WT neurovirulence was regained in vivo, suggesting a role for the capsid mutations in Brunenders attenuation. To date, as polio eradication draws closer, the switch to using attenuated strains for IPV is actively being pursued. Brunenders preceded this novel strategy as a partially attenuated IPV strain, accompanied by decades of successful use in the field. Providing data on the attenuation of Brunenders may be of value in the further construction of attenuated PV strains to support the grand pursuit of the global eradication of poliomyelitis.
authors.affiliation: Janssen Infectious Diseases and Vaccines, Leiden, The Netherlands.
authors.forename: Barbara P
authors.initials: BP
authors.lastname: Sanders
authors.affiliation: Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794-5222, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Janssen Infectious Diseases and Vaccines, Leiden, The Netherlands.
authors.forename: Alies
authors.initials: A
authors.lastname: Brandjes
authors.affiliation: Janssen Infectious Diseases and Vaccines, Leiden, The Netherlands.
authors.forename: Vladimir
authors.initials: V
authors.lastname: van Hoek
authors.affiliation: Janssen Infectious Diseases and Vaccines, Leiden, The Netherlands.
authors.forename: Isabel
authors.initials: I
authors.lastname: de Los Rios Oakes
authors.affiliation: Janssen Infectious Diseases and Vaccines, Leiden, The Netherlands.
authors.forename: John
authors.initials: J
authors.lastname: Lewis
authors.affiliation: Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794-5222, USA.
authors.forename: Eckard
authors.initials: E
authors.lastname: Wimmer
authors.affiliation: Janssen Infectious Diseases and Vaccines, Leiden, The Netherlands.
authors.forename: Jerome H H V
authors.initials: JHHV
authors.lastname: Custers
authors.affiliation: Janssen Infectious Diseases and Vaccines, Leiden, The Netherlands.
authors.forename: Hanneke
authors.initials: H
authors.lastname: Schuitemaker
authors.affiliation: Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794-5222, USA.
authors.forename: Jeronimo
authors.initials: J
authors.lastname: Cello
authors.affiliation: Janssen Infectious Diseases and Vaccines, Leiden, The Netherlands.
authors.forename: Diana
authors.initials: D
authors.lastname: Edo-Matas
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D049673:History, 20th Century; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D011051:Poliomyelitis / Q000266:history / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D017955:Poliovirus / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D011055:Poliovirus Vaccine, Oral / Q000737:chemistry / Q000235:genetics / Q000266:history / Q000276:immunology*; D016415:Sequence Alignment; D014613:Vaccines, Attenuated / Q000737:chemistry / Q000235:genetics / Q000266:history / Q000276:immunology
chemical_list: D011055:Poliovirus Vaccine, Oral; D014613:Vaccines, Attenuated