Protection of Neonates from Respiratory Syncytial Virus Infection

Respiratory syncytial virus (RSV) is the primary cause of acute lower respiratory tract infections in infants and young children worldwide, accounting for 33.8 million infections in 2005 alone. No licensed vaccine exists and, furthermore, direct vaccination of infants is likely ineffective, due to the immaturity of their immune system, and is potentially unsafe. Our long-term goal is to protect newborns from RSV infections through the passive transfer of maternal neutralizing antibodies in utero to the fetus after maternal immunization. A complicating issue with maternal immunization is that most people have experienced RSV infections during their lifetimes. But these infections do not result in maternal antibodies that can protect neonates. Thus any vaccine must induce in mothers high levels of neutralizing antibodies in the presence of pre-existing, but very poorly neutralizing, anti-RSV antibodies. We have developed a novel RSV vaccine candidate unlike any previously tested. Our candidate is a virus-like particle (VLP) containing a stabilized pre-fusion form of the RSV F protein (Pre-F), the biologically active conformation of the molecule that is most effective in stimulation of neutralizing antibodies. It is our hypothesis that immunization of mothers during pregnancy with the Pre-F containing VLPs will significantly boost their serum neutralizing antibodies responses, even in mothers with a past history of RSV infection. Using cotton rats as surrogates for human populations, we propose four specific aims to test this hypothesis.

Specific Aim 1: Assess the role of preexisting immunity in induction of neutralizing antibodies by Pre-F VLP Immunization
Specific Aim 2: Measure the transfer of maternal anti-RSV neutralizing antibodies, after Pre-F VLP vaccination, to neonates
Specific Aim 3: Evaluate protection of offspring of VLP immunized mothers from RSV challenge
Specific Aim 4: Assess potential for enhanced respiratory disease (lung pathology) in RSV infected offspring of VLP immunized mothers