title: A human respiratory syncytial virus (RSV) primate model of enhanced pulmonary pathology induced with a formalin-inactivated RSV vaccine but not a recombinant FG subunit vaccine.
abstract: Human respiratory syncytial virus (RSV) is the leading cause of severe bronchiolitis and pneumonia in infants. RSV vaccine development has been stifled for the past 23 years because infants vaccinated with formalin-inactivated (FI) RSV have experienced exacerbated disease upon RSV infection. This exacerbated disease phenomenon is poorly understood, in part because of the lack of a primate model that exhibits a similar exacerbated disease state. Vaccination of African green monkeys with either FI RSV or a genetically engineered subunit vaccine termed FG glycoprotein reduced replication of challenge virus. However, only vaccination with FI RSV induced an enhanced pulmonary pathologic response to RSV infection. Pulmonary inflammatory scores in the FG glycoprotein-vaccinated monkeys were no greater than in monkeys vaccinated with adjuvant alone. This is the first demonstration of RSV vaccine-induced enhanced pathology in a primate and illustrates that a subunit vaccine has the potential of circumventing this exacerbated disease phenomenon.
authors.affiliation: Drug Safety Research and Infectious Diseases Research, Upjohn Co., Kalamazoo, Michigan.
authors.forename: T J
authors.initials: TJ
authors.lastname: Kakuk
authors.forename: K
authors.initials: K
authors.lastname: Soike
authors.forename: R J
authors.initials: RJ
authors.lastname: Brideau
authors.forename: R M
authors.initials: RM
authors.lastname: Zaya
authors.forename: S L
authors.initials: SL
authors.lastname: Cole
authors.forename: J Y
authors.initials: JY
authors.lastname: Zhang
authors.forename: E D
authors.initials: ED
authors.lastname: Roberts
authors.forename: P A
authors.initials: PA
authors.lastname: Wells
authors.forename: M W
authors.initials: MW
authors.lastname: Wathen
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D005557:Formaldehyde; D015707:HN Protein; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008171:Lung Diseases / Q000209:etiology* / Q000473:pathology; D012136:Respiratory Syncytial Viruses / Q000276:immunology* / Q000302:isolation & purification; D010253:Respirovirus Infections / Q000209:etiology* / Q000473:pathology; D013997:Time Factors; D015164:Vaccines, Inactivated / Q000009:adverse effects / Q000276:immunology; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000276:immunology; D014759:Viral Envelope Proteins; D014764:Viral Proteins / Q000276:immunology*; D014765:Viral Vaccines / Q000009:adverse effects* / Q000276:immunology; D017201:Virus Shedding
chemical_list: D000914:Antibodies, Viral; D015707:HN Protein; D015164:Vaccines, Inactivated; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014764:Viral Proteins; D014765:Viral Vaccines; C116204:attachment protein G; D005557:Formaldehyde