title: Suppressing active replication of a live attenuated simian immunodeficiency virus vaccine does not abrogate protection from challenge.
abstract: Although safety concerns preclude the use of live attenuated HIV vaccines in humans, they provide a useful system for identifying the elusive correlates of protective immunity in the SIV/macaque animal model. However, a number of pieces of evidence suggest that protection may result from prior occupancy of susceptible target cells by the vaccine virus rather than the immune response. To address this, we developed a Nef-deletion variant of an RT-SHIV whose active replication could be shut off by treatment with RT-inhibitors. Groups of macaques were inoculated with the ∆Nef-RT-SHIV and immune responses allowed to develop before antiretroviral treatment and subsequent challenge with wild-type SIVmac239. Vaccinated animals either resisted infection fully or significantly controlled the subsequent viremia. However, there was no difference between animals undergoing replication of the vaccine virus and those without. This strongly suggests that competition for available target cells does not play a role in protection.
authors.affiliation: Robert Koch-Institut, Berlin, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Gabriel
authors.affiliation: Robert Koch-Institut, Berlin, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Fiebig
authors.affiliation: Robert Koch-Institut, Berlin, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Hohn
authors.affiliation: Paul-Ehrlich-Institut, Langen, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Plesker
authors.affiliation: Paul-Ehrlich-Institut, Langen, Germany.
authors.forename: Cheick
authors.initials: C
authors.lastname: Coulibaly
authors.affiliation: Paul-Ehrlich-Institut, Langen, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Cichutek
authors.affiliation: Paul-Ehrlich-Institut, Langen, Germany.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Mühlebach
authors.affiliation: Robert Koch-Institut, Berlin, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Bannert
authors.affiliation: Robert Koch-Institut, Berlin, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Kurth
authors.affiliation: Robert Koch-Institut, Berlin, Germany. Electronic address: NorleyS@rki.de.
authors.forename: Stephen
authors.initials: S
authors.lastname: Norley
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014766:Viremia / Q000276:immunology / Q000821:virology; D014779:Virus Replication
chemical_list: D016915:AIDS Vaccines; D000914:Antibodies, Viral; D014613:Vaccines, Attenuated