title: 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.
abstract: Post-infectious immunity to respiratory syncytial virus (RSV) infection results in limited protection as evidenced by the high rate of infant hospitalization in the face of high titer, maternally derived RSV-specific antibodies. By contrast, RSV fusion (F) glycoprotein antigenic site II humanized monoclonal antibodies, palivizumab and motavizumab, have been shown to reduce RSV-related hospitalization in infants. Immunogenicity and efficacy studies were conducted in cotton rats comparing a recombinant RSV F nanoparticle vaccine with palivizumab and controlled with live RSV virus intranasal immunization and, formalin inactivated RSV vaccine. Active immunization with RSV F nanoparticle vaccine containing an alum adjuvant induced serum levels of palivizumab competing antibody (PCA) greater than passive administration of 15 mg/kg palivizumab (human prophylactic dose) in cotton rats and neutralized RSV-A and RSV-B viruses. Immunization prevented detectable RSV replication in the lungs and, unlike passive administration of palivizumab, in the nasal passage of challenged cotton rats. Histology of lung tissues following RSV challenge showed no enhanced disease in the vaccinated groups in contrast to formalin inactivated 'Lot 100' vaccine. Passive intramuscular administration of RSV F vaccine-induced immune sera one day prior to challenge of cotton rats reduced viral titers by 2 or more log10 virus per gram of lung and nasal tissue and at doses less than palivizumab. A recombinant RSV F nanoparticle vaccine protected lower and upper respiratory tract against both RSV A and B strain infection and induced polyclonal palivizumab competing antibodies similar to but potentially more broadly protective against RSV than palivizumab.
authors.affiliation: Novavax Inc., 20 Firstfield Road, Gaithersburg MD 20878, United States. Electronic address: rraghunandan@novavax.com.
authors.forename: Rama
authors.initials: R
authors.lastname: Raghunandan
authors.affiliation: Novavax Inc., 20 Firstfield Road, Gaithersburg MD 20878, United States.
authors.forename: Hanxin
authors.initials: H
authors.lastname: Lu
authors.affiliation: Novavax Inc., 20 Firstfield Road, Gaithersburg MD 20878, United States.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Novavax Inc., 20 Firstfield Road, Gaithersburg MD 20878, United States.
authors.forename: Mimi Guebre
authors.initials: MG
authors.lastname: Xabier
authors.affiliation: Novavax Inc., 20 Firstfield Road, Gaithersburg MD 20878, United States.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Massare
authors.affiliation: Novavax Inc., 20 Firstfield Road, Gaithersburg MD 20878, United States.
authors.forename: David C
authors.initials: DC
authors.lastname: Flyer
authors.affiliation: Novavax Inc., 20 Firstfield Road, Gaithersburg MD 20878, United States.
authors.forename: Louis F
authors.initials: LF
authors.lastname: Fries
authors.affiliation: Novavax Inc., 20 Firstfield Road, Gaithersburg MD 20878, United States.
authors.forename: Gale E
authors.initials: GE
authors.lastname: Smith
authors.affiliation: Novavax Inc., 20 Firstfield Road, Gaithersburg MD 20878, United States.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Glenn
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D007116:Immunization, Passive; D008168:Lung / Q000473:pathology / Q000821:virology; D053758:Nanoparticles; D009500:Neutralization Tests; D000069455:Palivizumab; D011994:Recombinant Proteins / Q000276:immunology; D018357:Respiratory Syncytial Virus Infections / Q000517:prevention & control*; D022261:Respiratory Syncytial Virus Vaccines / Q000276:immunology*; D012136:Respiratory Syncytial Viruses; D061987:Sf9 Cells; D016205:Sigmodontinae; D014611:Vaccination; D015164:Vaccines, Inactivated / Q000276:immunology; D014760:Viral Fusion Proteins / Q000276:immunology*; D019562:Viral Load
chemical_list: D000276:Adjuvants, Immunologic; D061067:Antibodies, Monoclonal, Humanized; D000914:Antibodies, Viral; C526850:F protein, human respiratory syncytial virus; D011994:Recombinant Proteins; D022261:Respiratory Syncytial Virus Vaccines; D015164:Vaccines, Inactivated; D014760:Viral Fusion Proteins; D000069455:Palivizumab
keywords: Baculovirus; Cotton rat; Motavizumab; Nanoparticles; Palivizumab; Respiratory syncytial virus; Sf9 cells; Vaccine