A randomized, double-blind, placebo controlled study was carried out to determine the safety and immunogenicity of RSV PFP-2 vaccine (Wyeth-Lederle Vaccines, NY) in 35 healthy women in the third trimester of pregnancy and their offspring. Infants were followed during their first RSV season for occurrence and severity of respiratory illnesses. RSV-PFP-2 vaccine was safe and well tolerated by pregnant women. Mild pain at the site of injection occurred in 65% of PFP-2 and 13% of placebo recipients (P=0.005). There were no systemic reactions, fever, or serious adverse events associated with vaccine administration in mothers. All 35 infants were born healthy, and there were no differences among the groups in perinatal or neonatal outcomes, growth and development in the first year of life. During the RSV season, there was no increase in the frequency or morbidity associated with respiratory tract illnesses in infants of vaccine recipients. 15/20 (75%) vaccine recipients had a response to PFP-2 by Western blot vs. 0/15 placebo recipients (P<0.01). 19/20 (95%) vaccine recipients had a > or =4 fold rise in IgG ELISA Ab after immunization with PFP-2 vs. 0/15 placebo recipients (P<0.01). Geometric mean concentrations of IgG ELISA Ab were 4 fold higher in infants of vaccine recipients at birth, 2 and 6 months after delivery than in infants of placebo recipients (P<0.01). A modest (0.5log2) increase in neutralization Ab was observed in vaccine recipients and their infants. The half-life of maternal antibodies in infants was > or =3 weeks. There was no evidence of enhanced T-cell or cytokine activity in infants of vaccine recipients vs. infants of placebo recipients. Vaccine specific anti-F IgA and IgG concentrations in breast milk were higher in mothers who received RSV-PFP-2.