PFP-1 vaccine was evaluated in a randomized, controlled study in 47 RSV seropositive children. Trivalent inactivated influenza virus (TIV) vaccine was the control. Vaccine reactions were monitored, and bloods were obtained before vaccination, 4 weeks after vaccination, and at the end of the RSV season. Respiratory illnesses were evaluated during the outbreak. Neutralizing antibody (Nt Ab) assay to RSV, IgG ELISA to RSV proteins and a Western blot assay were performed. Acute reactions with the PFP vaccine were mild. An early RSV outbreak resulted in infection of 44.4% of the TIV recipients shortly after vaccination. In the PFP vaccine groups, the Nt Ab and ELISA assays did not distinguish between Ab rises due to natural infection versus vaccine; however, the Western blot assay characterized the post-vaccine rises. Two major Western blot profiles were produced: an infection profile (antibodies that recognized the F and G surface glycoproteins and internal proteins) and a vaccine profile (antibodies that recognized only the surface glycoproteins). The PFP vaccinees who were not infected with RSV developed ELISA and Nt Ab responses to the surface glycoproteins that were similar to the TIV vaccines with natural RSV infection. None of the children developed vaccine-enhanced disease. Thus, the PFP-1 vaccine was safe and immunogenic in RSV seropositive children even when vaccine was administered during a RSV outbreak, and the Western blot assay was useful in distinguishing Ab rises caused by RSV infection versus PFP vaccine.