Assessment of immunization against recombinant human bone morphogenetic protein-2 (dibotermin alpha) on reproduction and development in rabbits

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. Birth Defects Res (Part B) 92:543–552, 2011. © 2011 Wiley Periodicals, Inc.