GAITHERSBURG, Md.—Novavax, Inc., a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of recombinant nanoparticle vaccines and adjuvants, today announced that its RSV F-protein nanoparticle vaccine candidate (RSV F Vaccine) evoked a polyclonal antibody response to antigenic site II, the same site targeted by the monoclonal antibody palivizumab (Synagis®), resulting in protection from an RSV challenge in an animal model. Researchers at Novavax reported these findings in an online paper published by Vaccine titled: “An insect cell derived respiratory syncytial virus (RSV) F nanoparticle vaccine induces antigenic site II antibodies and protects against RSV challenge in cotton rats by active and passive immunization.”
“This study further characterizes the immune response to our RSV F vaccine, including the production of both polyclonal palivizumab competing antibodies that target antigenic site II, as well as other neutralizing antigenic sites on the F-protein,” said Greg Glenn, SVP, research and development at Novavax. “In addition, our ability to assess the safety of our RSV F vaccine relative to Lot 100 formalin inactivated vaccine, which is known to cause disease enhancement, and to demonstrate that our vaccine’s efficacy is equivalent or better than palivizumab, gives us greater confidence that our RSV vaccine candidate will be both safe and effective.”
Glenn characterizes RSV as “as 60-year puzzle.” He notes that Medimmune’s palivizumab was found empirically to be protective in cotton rats and that it is aimed at very premature infants and those with heart or lung disease. RSV is the number one cause of hospitalization in infants ages 0 to 12 months in the U.S. and is a significant cause of infant morbidity and mortality globally. Palivizumab, marketed as Synagis® by MedImmune/AstraZeneca, is the only approved product in the U.S. for the prevention of RSV disease in this population.
Palivizumab binds to a specific domain on the RSV F-protein known as antigenic site II, blocking viral fusion and preventing infection. Novavax has developed a novel RSV vaccine candidate based on the expression of a mature form of the RSV F-protein, which exposes the antigenic site II for processing by the immune system. The resulting immune response produces polyclonal antibodies that have been shown to compete with palivizumab for the antigenic site II binding domain, referred to as palivizumab-competing antibodies or PCA.
The study employed a number of antibody assays to further explore the immunogenicity of the RSV F vaccine and the production of vaccine-induced PCA in the cotton rat model. These studies used palivizumab as a control, to assess relative potency of the vaccine, both in active and passive assessments, and the recently available Lot 100 formalin-inactivated RSV vaccine, which historically enhanced RSV disease in clinical studies. This allowed comparative evaluation of safety, ‘functional’ immunity as measured by PCA and neutralization assays, and protection in this clinically relevant model. The vaccine was shown to be safe, potent, to elicit high levels of neutralizing PCA and anti-F antibodies and to be protective against both homologous strain and heterologous, or “drift”, strain viral challenges. The protection seen with active immunization could be reproduced using passively injected immune sera and appeared as potent as, or more potent than palivizumab. Neither active immunization of vaccine nor passively injected immune sera were associated with disease enhancement. Finally, the RSV F vaccine was also found to elicit antibodies that are known to bind other non-palivizumab F- protein binding sites associated with neutralization. “When we immunize,” Glenn states, “we have all of these sites. We are now entering into the stage of evaluating efficacy with tremendous confidence.”
“We have started two trials in the last 30 days,” notes CEO Stan Erck. “In the first RSV Phase 2 trial we will enroll 50 pregnant women in their third trimester to determine antibody levels in newborns. the elderly RSV Phase 2 trial plans to enroll 1600 healthy adults over 60 years of age. The maternal trial was the first to initiate: A third will be a pediatric study in one-to-five year olds.”
RSV is a major respiratory pathogen in infants, children, and adults. RSV infections in adults represent re-infections and are generally mild to moderate in severity, except in persons with high-risk conditions, including the elderly and adults with underlying chronic cardiac or pulmonary disease. It is estimated that between 11,000 and 17,000 adults die of RSV infection annually in the U.S. and up to 180,000 are admitted to hospitals with respiratory symptoms. Currently, there is no approved RSV prophylactic vaccine available. Palivizumab is a monoclonal antibody, licensed and sold by Medimmune as Synagis®, that targets the RSV F protein and is used for prophylaxis against RSV disease in high risk infants.
Novavax, Inc. is a clinical-stage biopharmaceutical company creating novel vaccines and vaccine adjuvants to address a broad range of infectious diseases worldwide. Using innovative proprietary recombinant nanoparticle vaccine technology, the company produces vaccine candidates to efficiently and effectively respond to both known and newly emergent diseases.