ICAAC Presentation: Immunization of Pregnant Baboons With the RSV F Nanoparticle Vaccine Protects Infant Baboons Challenged With Respiratory Syncytial Virus in a Comparable Manner to Infants Prophylaxed With Palivizumab
- Immunization of pregnant baboons generates anti-F IgG antibodies that are transferred from mothers to their infants
- When challenged with RSV, infant baboons born to immunized mothers show equivalent protection to infant baboons receiving palivizumab (Synagis ®) therapy
The ICAAC slide presentation 077:
Infant olive baboons develop RSV disease that mimics the clinical and pathological findings observed in human infants with RSV infection, making them an appropriate model for evaluation of maternal immunization with an RSV vaccine.
In this study, seronegative pregnant baboons (5 pairs) received either three intramuscular injections (IM) in the third trimester with a 60 μg/dose of the RSV vaccine and 1.2 mg of aluminum phosphate as an adjuvant at three week intervals, or saline. The paired infant baboons were challenged on day 30 intratracheally with 2-5x108pfu1 of respiratory syncytial virus (RSV). Similarly, 4 pairs of infant baboons were administered either 15mg/kg palivizumab or saline IM before the RSV challenge. Blood was collected on day 0 and bronchoalveolar lavage (BALs) was performed to assess lung viral load and leukocyte levels on day 0, 5, 7 and 10. Blinded observations of respiratory rates were made in pairs. Pulmonary function tests were performed in the infants of vaccinated and control mothers.
In recipients of the RSV F nanoparticle vaccine, antibody responses were measured in the mother on the day of birth (day 0 (zero)) and in the infant on day 30. Geometric mean anti-F IgG antibody titers were 115,535 Elisa Units (EU) and 32,774 EU, palivizumab competing antibodies (PCA) were 342 and 98 μg/ml and RSV A neutralizing antibodies (A MN) were 380 and 121, in the mothers and infants, respectively. Sera from infants administered palivizumab on day 29 had day 30 geometric mean anti-F IgG were 88,475 EU, PCA 196μg/ml and A MN 269. Palivizumab treated and infants of vaccinated mothers had significantly lower fold rise in respiratory rates compared to their matched, untreated pairs, (p=0.0008, and p=0.0028). Decreases in lung viral loads and BAL leukocytes were observed in treated infants. Reduced work of breathing and higher peak expiratory flow was observed in infants of vaccinated mothers.
"This study provides direct empirical evidence, in a relevant higher-primate model, to support the maternal immunization strategy for our RSV F nanoparticle vaccine," said
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 11-17,000 adults die of RSV infection annually in the U.S., with and up to 180,000 admitted to hospital 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.
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1 "Plaque Forming Units": PFU is a measurement of only those viral particles that will effectively produce a plaque and infect cells."
Barclay A. PhillipsSVP, Chief Financial Officer and Treasurer Novavax, Inc.240-268-2000