title: Modeling maternal fetal RSV F vaccine induced antibody transfer in guinea pigs.
abstract: BACKGROUND
  Protection of newborns and young infants against RSV disease via maternal immunization mediated by transplacental transfer of antibodies is under evaluation in third-trimester pregnant women with the RSV recombinant F nanoparticle vaccine (RSV F vaccine). Since the hemichorial placental architecture in guinea pigs and humans is similar, the guinea pig model was employed to assess RSV F vaccine immunogenicity in pregnant sows and to compare RSV-specific maternal antibody levels in their pups.
  
  
  METHODS
  Thirty (30) presumptive pregnant guinea pigs were immunized on gestational day 25 and 46 with placebo (PBS), 30μg RSV F, or 30μg RSV F+400μg aluminum phosphate. Sera at delivery/birth (sows/pups) and 15 and 30 days post-partum (pups) were analyzed for the presence of anti-F IgG, palivizumab-competitive antibody (PCA) and RSV/A microneutralization (MN).
  
  
  RESULTS
  The rates of pregnancy and stillbirth were similar between controls and vaccinees. The vaccine induced high levels of anti-F IgG, PCA and MN in sows, with the highest levels observed in adjuvanted vaccinees. Placental transfer to pups was proportional to the maternal antibody levels, with concentration effects observed for all immune measures.
  
  
  CONCLUSIONS
  The RSV F vaccine was safe and immunogenic in pregnant guinea pigs and supported robust transplacental antibody transfer to their pups. Relative concentration of antibodies in the pups was observed even in the presence of high levels of maternal antibody. Guinea pigs may be an important safety and immunogenicity model for preclinical assessment of candidate vaccines for maternal immunization.
authors: Novavax, Inc., 20 Firstfield Road, Gaithersburg, MD 20878, USA. Electronic address: gglenn@novavax.com.
authors: Gregory M
authors: GM
authors: Glenn
authors: Novavax, Inc., 20 Firstfield Road, Gaithersburg, MD 20878, USA.
authors: Louis F
authors: LF
authors: Fries
authors: Novavax, Inc., 20 Firstfield Road, Gaithersburg, MD 20878, USA.
authors: Gale
authors: G
authors: Smith
authors: Novavax, Inc., 20 Firstfield Road, Gaithersburg, MD 20878, USA.
authors: Eloi
authors: E
authors: Kpamegan
authors: Novavax, Inc., 20 Firstfield Road, Gaithersburg, MD 20878, USA.
authors: Hanxin
authors: H
authors: Lu
authors: Novavax, Inc., 20 Firstfield Road, Gaithersburg, MD 20878, USA.
authors: Mimi
authors: M
authors: Guebre-Xabier
authors: Novavax, Inc., 20 Firstfield Road, Gaithersburg, MD 20878, USA.
authors: Somia P
authors: SP
authors: Hickman
authors: Novavax, Inc., 20 Firstfield Road, Gaithersburg, MD 20878, USA.
authors: David
authors: D
authors: Flyer
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D017607:Aluminum Compounds / Q000008:administration & dosage; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood*; D005260:Female; D006168:Guinea Pigs; D007112:Immunity, Maternally-Acquired; D007118:Immunoassay; D007074:Immunoglobulin G / Q000097:blood; D018811:Maternal Exposure; D010710:Phosphates / Q000008:administration & dosage; D010919:Placebos / Q000008:administration & dosage; D011247:Pregnancy; D022261:Respiratory Syncytial Virus Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D014760:Viral Fusion Proteins / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D017607:Aluminum Compounds; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; C526850:F protein, human respiratory syncytial virus; D007074:Immunoglobulin G; D010710:Phosphates; D010919:Placebos; D022261:Respiratory Syncytial Virus Vaccines; D014760:Viral Fusion Proteins; C012714:aluminum phosphate
keywords: Anti-F IgG; Guinea pig; Hemichorial placenta; Maternal immunization; Microneutralization; Palivizumab-competitive antibody; RSV; RSV F nanoparticle vaccine; Transplacental antibody transfer