title: Live attenuated simian immunodeficiency virus vaccination confers superinfection resistance against macrophage-tropic and neurovirulent wild-type SIV challenge.
abstract: Vaccination with live attenuated simian immunodeficiency virus (SIV) in non-human primate species provides a means of characterizing the protective processes of retroviral superinfection and may lead to novel advances of human immunodeficiency virus (HIV)/AIDS vaccine design. The minimally attenuated SIVmacC8 vaccine has been demonstrated to elicit early potent protection against pathogenic rechallenge with genetically diverse viral isolates in cynomolgus macaques (Macaca fascicularis). In this study, we have characterized further the biological breadth of this vaccine protection by assessing the ability of both the nef-disrupted SIVmacC8 and its nef-intact counterpart SIVmacJ5 viruses to prevent superinfection with the macrophage/neurotropic SIVmac239/17E-Fr (SIVmac17E-Fr) isolate. Inoculation with either SIVmacC8 or SIVmacJ5 and subsequent detailed characterization of the viral replication kinetics revealed a wide range of virus-host outcomes. Both nef-disrupted and nef-intact immunizing viruses were able to prevent establishment of SIVmac17E-Fr in peripheral blood and secondary lymphoid tissues. Differences in virus kinetics, indicative of an active process, identified uncontrolled replication in one macaque which although able to prevent SIVmac17E-Fr superinfection led to extensive neuropathological complications. The ability to prevent a biologically heterologous, CD4-independent/CCR5+ viral isolate and the macrophage-tropic SIVmac316 strain from establishing infection supports the hypothesis that direct target cell blocking is unlikely to be a central feature of live lentivirus vaccination. These data provide further evidence to demonstrate that inoculation of a live retroviral vaccine can deliver broad spectrum protection against both macrophage-tropic as well as lymphocytotropic viruses. These data add to our knowledge of live attenuated SIV vaccines but further highlight potential safety concerns of vaccinating with a live retrovirus.
authors.affiliation: 1Division of Virology, NIBSC, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK.
authors.forename: Neil
authors.initials: N
authors.lastname: Berry
authors.affiliation: 1Division of Virology, NIBSC, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK.
authors.forename: Claire
authors.initials: C
authors.lastname: Ham
authors.affiliation: 1Division of Virology, NIBSC, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK.
authors.forename: Jack
authors.initials: J
authors.lastname: Alden
authors.affiliation: 1Division of Virology, NIBSC, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK.
authors.forename: Sean
authors.initials: S
authors.lastname: Clarke
authors.affiliation: 2Divison of Biotherapeutics, NIBSC, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Stebbings
authors.affiliation: 1Division of Virology, NIBSC, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK.
authors.forename: Jim
authors.initials: J
authors.lastname: Stott
authors.affiliation: 1Division of Virology, NIBSC, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK.
authors.forename: Deborah
authors.initials: D
authors.lastname: Ferguson
authors.affiliation: 1Division of Virology, NIBSC, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK.
authors.forename: Neil
authors.initials: N
authors.lastname: Almond
mesh_terms: D000818:Animals; D008252:Macaca fascicularis; D008264:Macrophages / Q000821:virology; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D015163:Superinfection / Q000517:prevention & control; D014611:Vaccination / Q000379:methods*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D018449:SAIDS Vaccines; D014613:Vaccines, Attenuated
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