Phase 1 evaluation of the respiratory syncytial virus-specific monoclonal antibody palivizumab in recipients of hematopoietic stem cell transplants.

Intravenous palivizumab (15 mg/kg) was investigated in 2 phase 1 studies among recipients of hematopoietic stem cell transplants (HSCTs). Study 1 included 6 HSCT patients without active respiratory syncytial virus (RSV) infection. Study 2 included 15 HSCT patients with RSV upper respiratory tract infection (URTI; n=3) or RSV interstitial pneumonia (IP; n=12), all of whom also received aerosolized ribavirin. Peak serum concentrations of palivizumab in the 2 studies were similar. The mean serum half-life was 22.4 days in study 1, which mainly included autologous HSCT recipients, and 10.7 days in study 2, which mainly included allogeneic HSCT recipients. No antibodies to palivizumab were detected in study 1. No adverse events were attributed to palivizumab in the 2 studies. In study 2, all 3 patients with RSV URTI recovered without progression to lower respiratory tract disease, and 10 (83%) of the 12 patients with RSV IP survived the 28-day study period. Thus, palivizumab appears to be safe and well tolerated in HSCT recipients.

A Phase 1 study of a recombinant viruslike particle vaccine against human papillomavirus type 11 in healthy adult volunteers.

Viruslike particles (VLPs) produced from the L1 protein of several papillomaviruses have induced protection from infection after live challenge in animal models. In the present study, the safety and immunogenicity of a human papillomavirus (HPV)--11 L1 VLP candidate vaccine were measured in a phase 1, dose-finding trial in humans. The vaccine was well tolerated and induced high levels of both binding and neutralizing antibodies. Marked increases in lymphoproliferation to HPV--11 L1 antigens were noted after the second vaccination. In addition, lymphoproliferation was induced after vaccination in peripheral blood mononuclear cells (PBMC) stimulated with heterologous L1 VLP antigens of HPV types 6 and 16. Statistically significant increases in HPV antigen--specific interferon--gamma and interleukin-5 production were measured from PBMC culture supernatants. This candidate HPV VLP vaccine induced robust B and T cell responses, and T cell helper epitopes appear to be conserved across HPV types.

Reduction of respiratory syncytial virus (RSV) in tracheal aspirates in intubated infants by use of humanized monoclonal antibody to RSV F protein.

Thirty-five children <2 years of age mechanically ventilated for respiratory syncytial virus (RSV) infection were randomized to receive an intravenous infusion of 15 mg/kg MEDI-493 or placebo. RSV concentration was measured in tracheal secretions by plaque assay before and at 24-h intervals after treatment. The reduction in tracheal RSV concentration from day 0 to day 1 (-1.7+/-0.28 vs. -0. 6+/-0.21 log10 pfu/mL; P=.004) and from day 0 to day 2 (-2.5+/-0.26 vs. -1.0+/-0.41 log10 pfu/mL; P=.012) was significantly greater in the MEDI-493 group than in the placebo group. RSV concentration in nasal aspirates did not differ significantly between the groups. No significant differences were observed in the tracheal aspirate white blood cell count, or myeloperoxidase or eosinophilic cationic protein concentration, or in measures of disease severity between the groups. Thus, treatment with 15 mg/kg MEDI-493 intravenously was well-tolerated and significantly reduced RSV concentration in tracheal aspirates of children with respiratory failure due to RSV.