title: Immune suppression of challenged vaccinates as a rigorous assessment of sterile protection by lentiviral vaccines.
abstract: We previously reported that an experimental live-attenuated equine infectious anemia virus (EIAV) vaccine, containing a mutated S2 accessory gene, provided protection from disease and detectable infection after virulent virus (EIAV(PV)) challenge [Li F, Craigo JK, Howe L, Steckbeck JD, Cook S, Issel C, et al. A live-attenuated equine infectious anemia virus proviral vaccine with a modified S2 gene provides protection from detectable infection by intravenous virulent virus challenge of experimentally inoculated horses. J Virol 2003;77(13):7244-53; Craigo JK, Li F, Steckbeck JD, Durkin S, Howe L, Cook SJ, et al. Discerning an effective balance between equine infectious anemia virus attenuation and vaccine efficacy. J Virol 2005;79(5):2666-77]. To determine if attenuated EIAV vaccines actually prevent persistent infection by challenge virus, we employed a 14-day dexamethasone treatment of vaccinated horses post-challenge to suppress host immunity and amplify replication levels of any infecting EIAV. At 2 months post-challenge the horses were all protected from virulent-virus challenge, evidenced by a lack of EIA signs and detectable challenge plasma viral RNA. Upon immune suppression, 6/12 horses displayed clinical EIA. Post-immune suppression characterizations demonstrated that the attenuated vaccine evidently prevented detectable challenge virus infection in 50% of horses. These data highlight the utility of post-challenge immune suppression for evaluating persistent viral vaccine protective efficacy.
authors.affiliation: Department of Molecular Genetics and Biochemistry, W1144 Biomedical Science Tower, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, United States.
authors.forename: Jodi K
authors.initials: JK
authors.lastname: Craigo
authors.forename: Shannon
authors.initials: S
authors.lastname: Durkin
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Sturgeon
authors.forename: Tara
authors.initials: T
authors.lastname: Tagmyer
authors.forename: Sheila J
authors.initials: SJ
authors.lastname: Cook
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Issel
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Montelaro
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001483:Base Sequence; D003907:Dexamethasone / Q000494:pharmacology*; D004859:Equine Infectious Anemia / Q000517:prevention & control; D005260:Female; D006736:Horses; D004860:Infectious Anemia Virus, Equine / Q000276:immunology*; D008297:Male; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination; D014613:Vaccines, Attenuated; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D012367:RNA, Viral; D014613:Vaccines, Attenuated; D014765:Viral Vaccines; D003907:Dexamethasone