title: Generation of a parvovirus B19 vaccine candidate.
abstract: Parvovirus B19 is the causative agent of fifth disease in children, aplastic crisis in those with blood dyscrasias, and hydrops fetalis. Previous parvovirus B19 virus-like-particle (VLP) vaccine candidates were produced by co-infection of insect cells with two baculoviruses, one expressing wild-type VP1 and the other expressing VP2. In humans, the VLPs were immunogenic but reactogenic. We have developed new VLP-based parvovirus B19 vaccine candidates, produced by co-expressing VP2 and either wild-type VP1 or phospholipase-negative VP1 in a regulated ratio from a single plasmid in Saccharomyces cerevisiae. These VLPs are expressed efficiently, are very homogeneous, and can be highly purified. Although VP2 alone can form VLPs, in mouse immunizations, VP1 and the adjuvant MF59 are required to elicit a neutralizing response. Wild-type VLPs and those with phospholipase-negative VP1 are equivalently potent. The purity, homogeneity, yeast origin, and lack of phospholipase activity of these VLPs address potential causes of previously observed reactogenicity.
authors.affiliation: Novartis Vaccines, Cambridge, MA 02139, United States.
authors.forename: Sumana
authors.initials: S
authors.lastname: Chandramouli
authors.forename: Angelica
authors.initials: A
authors.lastname: Medina-Selby
authors.forename: Doris
authors.initials: D
authors.lastname: Coit
authors.forename: Mary
authors.initials: M
authors.lastname: Schaefer
authors.forename: Terika
authors.initials: T
authors.lastname: Spencer
authors.forename: Luis A
authors.initials: LA
authors.lastname: Brito
authors.forename: Pu
authors.initials: P
authors.lastname: Zhang
authors.forename: Gillis
authors.initials: G
authors.lastname: Otten
authors.forename: Christian W
authors.initials: CW
authors.lastname: Mandl
authors.forename: Peter W
authors.initials: PW
authors.lastname: Mason
authors.forename: Philip R
authors.initials: PR
authors.lastname: Dormitzer
authors.forename: Ethan C
authors.initials: EC
authors.lastname: Settembre
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D010322:Parvoviridae Infections / Q000276:immunology / Q000517:prevention & control; D016732:Parvovirus B19, Human / Q000235:genetics / Q000276:immunology*; D054467:Phospholipases A2 / Q000378:metabolism; D011136:Polysorbates; D012441:Saccharomyces cerevisiae / Q000235:genetics; D013185:Squalene / Q000276:immunology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000235:genetics* / Q000276:immunology* / Q000302:isolation & purification
chemical_list: D000276:Adjuvants, Immunologic; D036022:Capsid Proteins; C089950:MF59 oil emulsion; D011136:Polysorbates; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; C095547:capsid protein VP1, parvovirus B19; C095548:capsid protein VP2, parvovirus B19; D013185:Squalene; D054467:Phospholipases A2
keywords: Parvovirus B19; VLP; Vaccine; Virus-like particle