title: Development and preclinical evaluation of an alphavirus replicon particle vaccine for cytomegalovirus.
abstract: We used a replication-incompetent, single-cycle, alphavirus replicon vector system to produce virus-like replicon particles (VRP) expressing the extracellular domain of human cytomegalovirus (CMV) glycoprotein B or a pp65/IE1 fusion protein. Efficient production methods were scaled to produce pilot lots and clinical lots of each alphavirus replicon vaccine component. The vaccine induced high-titered antibody responses in mice and rabbits, as measured by ELISA and CMV neutralization assays, and robust T-cell responses in mice, as measured by IFN-gamma ELISPOT assay. A toxicity study in rabbits showed no adverse effects in any toxicology parameter. These studies support clinical testing of this novel CMV alphavirus replicon vaccine in humans.
authors.affiliation: AlphaVax Inc., Research Triangle Park, NC 27709, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Reap
authors.forename: John
authors.initials: J
authors.lastname: Morris
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Dryga
authors.forename: Maureen
authors.initials: M
authors.lastname: Maughan
authors.forename: Todd
authors.initials: T
authors.lastname: Talarico
authors.forename: Robert E
authors.initials: RE
authors.lastname: Esch
authors.forename: Sarah
authors.initials: S
authors.lastname: Negri
authors.forename: Bruce
authors.initials: B
authors.lastname: Burnett
authors.forename: Andrew
authors.initials: A
authors.lastname: Graham
authors.forename: Robert A
authors.initials: RA
authors.lastname: Olmsted
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Chulay
mesh_terms: D000524:Alphavirus / Q000235:genetics*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D003587:Cytomegalovirus / Q000235:genetics* / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000517:prevention & control; D022482:Cytomegalovirus Vaccines / Q000235:genetics* / Q000276:immunology / Q000633:toxicity; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D007111:Immunity, Cellular; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000235:genetics; D011817:Rabbits; D012093:Replicon; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology / Q000633:toxicity
chemical_list: D000914:Antibodies, Viral; D022482:Cytomegalovirus Vaccines; D014614:Vaccines, Synthetic