title: Neutralizing antibody affords comparable protection against vaginal and rectal simian/human immunodeficiency virus challenge in macaques.
abstract: Passive administration of broadly neutralizing antibodies has been shown to protect against both vaginal and rectal challenge in the simian/human immunodeficiency virus (SHIV)/macaque model of HIV transmission. However, the relative efficacy of antibody against the two modes of exposure is unknown and, given differences in the composition and immunology of the two tissue compartments, this is an important gap in knowledge. To investigate the significance of the challenge route for antibody-mediated protection, we performed a comparative protection study in macaques using the highly potent human monoclonal antibody, PGT126.
  
  
  
  Animals were administered PGT126 at three different doses before challenged either vaginally or rectally with a single dose of SHIVSF163P3.
  
  
  
  Viral loads, PGT126 serum concentrations, and serum neutralizing titers were monitored.
  
  
  
  In vaginally challenged animals, sterilizing immunity was achieved in all animals administered 10 mg/kg, in two of five animals administered 2 mg/kg and in one of five animals administered 0.4 mg/kg PGT126. Comparable protection was observed for the corresponding groups challenged rectally as sterilizing immunity was achieved in three of four animals administered 10 mg/kg, in two of four animals administered 2 mg/kg and in none of four animals administered 0.4 mg/kg PGT126. Serological analysis showed similar serum concentrations of PGT126 and serum neutralization titers in animals administered the same antibody dose.
  
  
  
  Our data suggest that broadly neutralizing antibody-mediated protection is not strongly dependent on the mucosal route of challenge, which indicates that a vaccine aimed to induce a neutralizing antibody response would have broadly similar efficacy against both primary transmission routes for HIV.
authors.affiliation: aDepartment of Immunology and Microbial Science, IAVI Neutralizing Antibody Center and Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California bEmory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, Georgia cCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts dBioqual, Inc., Rockville, Maryland eBioinformatics and Systems Biology Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA fGenmab, Utrecht, The Netherlands gRagon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, USA. *Present address: MedImmune, LLC, Gaithersburg, Maryland, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Moldt
authors.forename: Khoa M
authors.initials: KM
authors.lastname: Le
authors.forename: Diane G
authors.initials: DG
authors.lastname: Carnathan
authors.forename: James B
authors.initials: JB
authors.lastname: Whitney
authors.forename: Niccole
authors.initials: N
authors.lastname: Schultz
authors.forename: Mark G
authors.initials: MG
authors.lastname: Lewis
authors.forename: Erica N
authors.initials: EN
authors.lastname: Borducchi
authors.forename: Kaitlin M
authors.initials: KM
authors.lastname: Smith
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Mackel
authors.forename: Shelby L
authors.initials: SL
authors.lastname: Sweat
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Hodges
authors.forename: Adam
authors.initials: A
authors.lastname: Godzik
authors.forename: Paul W H I
authors.initials: PW
authors.lastname: Parren
authors.forename: Guido
authors.initials: G
authors.lastname: Silvestri
authors.forename: Dan H
authors.initials: DH
authors.lastname: Barouch
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Burton
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005260:Female; D006678:HIV / Q000276:immunology*; D015483:HIV Antibodies / Q000008:administration & dosage*; D015658:HIV Infections / Q000517:prevention & control*; D008251:Macaca; D012007:Rectum / Q000276:immunology*; D016896:Treatment Outcome; D014621:Vagina / Q000276:immunology*; D019562:Viral Load
chemical_list: D057134:Antibodies, Neutralizing; D015483:HIV Antibodies