title: Safety and immunogenicity of a Sf9 insect cell-derived respiratory syncytial virus fusion protein nanoparticle vaccine.
abstract: OBJECTIVE
  We performed a Phase 1 randomized, observer-blinded, placebo-controlled trial to evaluate the safety and immunogenicity of a recombinant respiratory syncytial virus (RSV) fusion (F) protein nanoparticle vaccine.
  
  
  METHODS
  Six formulations with (5, 15, 30 and 60 μg) and without (30 and 60 μg) aluminum phosphate (AdjuPhos) were administered intramuscularly on day 0 and 30 in a dose escalating fashion to healthy adults 18-49 years of age. Solicited and unsolicited events were collected through day 210. Immunogenicity measures taken at day 0, 30 and 60 included RSV A and B microneutralization, anti-F IgG, antigenic site II peptide and palivizumab competitive antibodies.
  
  
  RESULTS
  The vaccine was well-tolerated, with no evident dose-related toxicity or attributable SAEs. At day 60 both RSV A and B microneutralization was significantly increased in vaccinees versus placebo. Across all vaccinees there was a 7- to 19-fold increase in the anti-F IgG and a 7- to 24-fold increase in the antigenic site II binding and palivizumab competitive antibodies.
  
  
  CONCLUSIONS
  The RSV F nanoparticle vaccine candidate was well tolerated without dose-related increases in adverse events. Measures of immunity indicate that neutralization, anti-RSV F IgG titers and palivizumab competing antibodies were induced at levels that have been associated with decreased risk of hospitalization. NCT01290419.
authors.affiliation: Novavax, Inc., Rockville, MD 20850, USA. GGlenn@novavax.com
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Glenn
authors.forename: Gale
authors.initials: G
authors.lastname: Smith
authors.forename: Louis
authors.initials: L
authors.lastname: Fries
authors.forename: Rama
authors.initials: R
authors.lastname: Raghunandan
authors.forename: Hanxin
authors.initials: H
authors.lastname: Lu
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.forename: D Nigel
authors.initials: DN
authors.lastname: Thomas
authors.forename: Somia P
authors.initials: SP
authors.lastname: Hickman
authors.forename: Eloi
authors.initials: E
authors.lastname: Kpamegan
authors.forename: Sarathi
authors.initials: S
authors.lastname: Boddapati
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Piedra
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects; D000293:Adolescent; D000328:Adult; D017607:Aluminum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D001709:Biotechnology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D053758:Nanoparticles / Q000008:administration & dosage / Q000009:adverse effects; D010710:Phosphates / Q000008:administration & dosage / Q000009:adverse effects; D010919:Placebos / Q000008:administration & dosage / Q000009:adverse effects; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects* / Q000235:genetics / Q000276:immunology*; D022261:Respiratory Syncytial Virus Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000235:genetics / Q000276:immunology*; D061987:Sf9 Cells; D016037:Single-Blind Method; D013678:Technology, Pharmaceutical; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D022721:Vaccines, Virosome / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D017607:Aluminum Compounds; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D010710:Phosphates; D010919:Placebos; D011993:Recombinant Fusion Proteins; D022261:Respiratory Syncytial Virus Vaccines; D014614:Vaccines, Synthetic; D022721:Vaccines, Virosome; C012714:aluminum phosphate