title: Adoptive transfer of lymphocytes isolated from simian immunodeficiency virus SIVmac239Δnef-vaccinated macaques does not affect acute-phase viral loads but may reduce chronic-phase viral loads in major histocompatibility complex-matched recipients.
abstract: The live attenuated simian immunodeficiency virus (SIV) SIVmac239Δnef is the most effective SIV/human immunodeficiency virus (HIV) vaccine in preclinical testing. An understanding of the mechanisms responsible for protection may provide important insights for the development of HIV vaccines. Leveraging the uniquely restricted genetic diversity of Mauritian cynomolgus macaques, we performed adoptive transfers between major histocompatibility complex (MHC)-matched animals to assess the role of cellular immunity in SIVmac239Δnef protection. We vaccinated and mock vaccinated donor macaques and then harvested between 1.25 × 10(9) and 3.0 × 10(9) mononuclear cells from multiple tissues for transfer into 12 naive recipients, followed by challenge with pathogenic SIVmac239. Fluorescently labeled donor cells were detectable for at least 7 days posttransfer and trafficked to multiple tissues, including lung, lymph nodes, and other mucosal tissues. There was no difference between recipient macaques' peak or postpeak plasma viral loads. A very modest difference in viral loads during the chronic phase between vaccinated animal cell recipients and mock-vaccinated animal cell recipients did not reach significance (P = 0.12). Interestingly, the SIVmac239 challenge virus accumulated escape mutations more rapidly in animals that received cells from vaccinated donors. These results may suggest that adoptive transfers influenced the course of infection despite the lack of significant differences in the viral loads among animals that received cells from vaccinated and mock-vaccinated donor animals.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Greene
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Lhost
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Hines
authors.forename: Matthew
authors.initials: M
authors.lastname: Scarlotta
authors.forename: Max
authors.initials: M
authors.lastname: Harris
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Burwitz
authors.forename: Melisa L
authors.initials: ML
authors.lastname: Budde
authors.forename: Dawn M
authors.initials: DM
authors.lastname: Dudley
authors.forename: Ngoc
authors.initials: N
authors.lastname: Pham
authors.forename: Brian
authors.initials: B
authors.lastname: Cain
authors.forename: Caitlin E
authors.initials: CE
authors.lastname: Mac Nair
authors.forename: Madelyn K
authors.initials: MK
authors.lastname: Weiker
authors.forename: Shelby L
authors.initials: SL
authors.lastname: O'Connor
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Friedrich
authors.forename: David H
authors.initials: DH
authors.lastname: O'Connor
mesh_terms: D000210:Acute-Phase Reaction / Q000276:immunology; D019264:Adoptive Transfer; D000818:Animals; D001483:Base Sequence; D019295:Computational Biology; D058501:Enzyme-Linked Immunospot Assay; D005434:Flow Cytometry; D005453:Fluorescence; D007111:Immunity, Cellular / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008252:Macaca fascicularis / Q000821:virology*; D008285:Major Histocompatibility Complex / Q000276:immunology; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D019562:Viral Load / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D014765:Viral Vaccines