title: Protection afforded by an HIV vaccine candidate in macaques depends on the dose of SIVmac251 at challenge exposure.
abstract: We used the simian immunodeficiency virus mac251 (SIV(mac251)) macaque model to study the effect of the dose of mucosal exposure on vaccine efficacy. We immunized macaques with a DNA prime followed by SIV gp120 protein immunization with ALVAC-SIV and gp120 in alum, and we challenged them with SIV(mac251) at either a single high dose or at two repeated low-dose exposures to a 10-fold-lower dose. Infection was neither prevented nor modified following a single high-dose challenge of the immunized macaques. However, two exposures to a 10-fold-lower dose resulted in protection from SIV(mac251) acquisition in 3 out of 12 macaques. The remaining animals that were infected had a modulated pathogenesis, significant downregulation of interferon responsive genes, and upregulation of genes involved in B- and T-cell responses. Thus, the choice of the experimental model greatly influences the vaccine efficacy of vaccines for human immunodeficiency virus (HIV).
authors: Animal Models and Retroviral Vaccine Section, National Cancer Institute, Bethesda, MD, USA.
authors: Monica
authors: M
authors: Vaccari
authors: Brandon F
authors: BF
authors: Keele
authors: Steven E
authors: SE
authors: Bosinger
authors: Melvin N
authors: MN
authors: Doster
authors: Zhong-Min
authors: ZM
authors: Ma
authors: Justin
authors: J
authors: Pollara
authors: Anna
authors: A
authors: Hryniewicz
authors: Guido
authors: G
authors: Ferrari
authors: Yongjun
authors: Y
authors: Guan
authors: Donald N
authors: DN
authors: Forthal
authors: David
authors: D
authors: Venzon
authors: Claudio
authors: C
authors: Fenizia
authors: Tia
authors: T
authors: Morgan
authors: David
authors: D
authors: Montefiori
authors: Jeffrey D
authors: JD
authors: Lifson
authors: Chris J
authors: CJ
authors: Miller
authors: Guido
authors: G
authors: Silvestri
authors: Margherita
authors: M
authors: Rosati
authors: Barbara K
authors: BK
authors: Felber
authors: George N
authors: GN
authors: Pavlakis
authors: James
authors: J
authors: Tartaglia
authors: Genoveffa
authors: G
authors: Franchini
mesh_terms: D000818:Animals; D015686:Gene Products, env / Q000235:genetics; D008251:Macaca; D008969:Molecular Sequence Data; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D017422:Sequence Analysis, DNA; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000472:pathogenicity*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology
chemical_list: D015686:Gene Products, env; D018449:SAIDS Vaccines; D019444:Vaccines, DNA; D022223:Vaccines, Subunit