title: A protein-based smallpox vaccine protects mice from vaccinia and ectromelia virus challenges when given as a prime and single boost.
abstract: The heightened concern about the intentional release of variola virus has led to the need to develop safer smallpox vaccines. While subunit vaccine strategies are safer than live virus vaccines, subunit vaccines have been hampered by the need for multiple boosts to confer optimal protection. Here we developed a protein-based subunit vaccine strategy that provides rapid protection in mouse models of orthopoxvirus infections after a prime and single boost. Mice vaccinated with vaccinia virus envelope proteins from the mature virus (MV) and extracellular virus (EV) adjuvanted with CpG ODN and alum were protected from lethal intranasal challenge with vaccinia virus and the mouse-specific ectromelia virus. Organs from mice vaccinated with three proteins (A33, B5 and L1) and then sacrificed after challenge contained significantly lower titers of virus when compared to control groups of mice that were not vaccinated or that received sub-optimal formulations of the vaccine. Sera from groups of mice obtained prior to challenge had neutralizing activity against the MV and also inhibited comet formation indicating anti-EV activity. Long-term partial protection was also seen in mice challenged with vaccinia virus 6 months after initial vaccinations. Thus, this work represents a step toward the development of a practical subunit smallpox vaccine.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6073, USA.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Xiao
authors.forename: Lydia
authors.initials: L
authors.lastname: Aldaz-Carroll
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Ortiz
authors.forename: J Charles
authors.initials: JC
authors.lastname: Whitbeck
authors.forename: Edward
authors.initials: E
authors.lastname: Alexander
authors.forename: Huan
authors.initials: H
authors.lastname: Lou
authors.forename: Heather L
authors.initials: HL
authors.lastname: Davis
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Braciale
authors.forename: Roselyn J
authors.initials: RJ
authors.lastname: Eisenberg
authors.forename: Gary H
authors.initials: GH
authors.lastname: Cohen
authors.forename: Stuart N
authors.initials: SN
authors.lastname: Isaacs
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D002626:Chemistry, Pharmaceutical; D020552:Comet Assay; D004481:Ectromelia virus / Q000276:immunology*; D004482:Ectromelia, Infectious / Q000276:immunology* / Q000517:prevention & control*; D005260:Female; D007115:Immunization Schedule; D007117:Immunization, Secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012900:Smallpox Vaccine / Q000276:immunology*; D013534:Survival; D014615:Vaccinia / Q000276:immunology* / Q000517:prevention & control*; D014616:Vaccinia virus / Q000276:immunology*; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D015431:Weight Loss / Q000187:drug effects
chemical_list: D000276:Adjuvants, Immunologic; D012900:Smallpox Vaccine; D014764:Viral Proteins