title: Rapid, repeated, low-dose challenges with SIVmac239 infect animals in a condensed challenge window.
abstract: BACKGROUND
  Simian immunodeficiency virus (SIV) infection of nonhuman primates is the predominant model for preclinical evaluation of human immunodeficiency virus (HIV) vaccines. These studies frequently utilize high-doses of SIV that ensure infection after a single challenge but do not recapitulate critical facets of sexual HIV transmission. Investigators are increasingly using low-dose challenges in which animals are challenged once every week or every two weeks in order to better replicate sexual HIV transmission. Using this protocol, some animals require over ten challenges before SIV infection is detectable, potentially inducing localized immunity. Moreover, the lack of certainty over which challenge will lead to productive infection prevents tissue sampling immediately surrounding the time of infection.
  
  
  RESULTS
  Here we challenged Mauritian cynomolgus macaques with 100 50% tissue culture infectious doses (TCID50) of SIVmac239 intrarectally three times a day for three consecutive days. Ten of twelve animals had positive plasma viral loads after this challenge regimen.
  
  
  CONCLUSIONS
  This approach represents a straightforward advance in SIV challenge protocols that may avoid induction of local immunity, avoid inconsistent timing between last immunization and infection, and allow sampling immediately after infection using low-dose challenge protocols.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Greene
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Weiler
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Reynolds
authors.forename: Brian T
authors.initials: BT
authors.lastname: Cain
authors.forename: Ngoc H
authors.initials: NH
authors.lastname: Pham
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Ericsen
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Peterson
authors.forename: Kristin
authors.initials: K
authors.lastname: Crosno
authors.forename: Kevin
authors.initials: K
authors.lastname: Brunner
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Friedrich
authors.forename: David H
authors.initials: DH
authors.lastname: O'Connor
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D007114:Immunization / Q000379:methods; D008251:Macaca; D008252:Macaca fascicularis / Q000276:immunology / Q000821:virology; D018449:SAIDS Vaccines / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D019562:Viral Load
chemical_list: D016915:AIDS Vaccines; D000914:Antibodies, Viral; D018449:SAIDS Vaccines