title: Assessment of immunization against recombinant human bone morphogenetic protein-2 (dibotermin alpha) on reproduction and development in rabbits.
abstract: BACKGROUND
  To determine if the fetus was affected by maternal antibodies to BMP-2, the antibody response and developmental effects in fetuses from does immunized against recombinant human BMP-2 were evaluated.
  
  
  METHODS
  Female New Zealand White rabbits received four intramuscular injections (on premating days 1, 8, 22, and 43 [3 days before mating]) of saline and adjuvant (TiterMax(®) Gold [control]) or recombinant human BMP-2 (2 mg/dose) and adjuvant (treated). On GD 29, fetuses were examined, and maternal and fetal anti-BMP-2 titer levels and neutralizing activity were assessed.
  
  
  RESULTS
  Anti-BMP-2 antibodies were detected in 17 of 18 treated does (127 of 151 fetuses), and low levels were detected in 2 of 16 control does (no fetal exposure observed). In general, levels of fetal anti-BMP-2 antibodies were similar to those in the does, and pregnancy did not boost the immune response to BMP-2. There were no effects of immunization or anti-BMP-2 antibody titer levels on embryo-fetal viability, fetal weight, or fetal external, visceral, or skeletal development. Only a small number of fetuses (n = 4) displayed detectable neutralizing anti-BMP-2 antibodies, but there were no treatment-related effects in those fetuses.
  
  
  CONCLUSIONS
  The lack of embryo-fetal effects may be due to dosage effects of neutralizing anti-BMP-2 antibodies, timing of exposure (stage and duration) to neutralizing anti-BMP-2 antibodies, and/or redundancy of effects of the various BMPs.
authors.affiliation: Drug Safety Research & Development, Pfizer, Groton, Connecticut, USA. david.wright@pfizer.com
authors.forename: David J
authors.initials: DJ
authors.lastname: Wright
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Minck
authors.forename: John
authors.initials: J
authors.lastname: Nowak
authors.forename: Garvin
authors.initials: G
authors.lastname: Warner
authors.forename: Mark
authors.initials: M
authors.lastname: Cukierski
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000097:blood; D057134:Antibodies, Neutralizing / Q000276:immunology; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism*; D047108:Embryonic Development; D005260:Female; D047109:Fetal Development; D006801:Humans; D007114:Immunization; D011247:Pregnancy; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D012098:Reproduction; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D057134:Antibodies, Neutralizing; D055396:Bone Morphogenetic Protein 2; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2