title: Nonreplicating vaccines can protect african green monkeys from the memphis 37 strain of respiratory syncytial virus.
abstract: BACKGROUND
  We evaluated the immunological responses of African green monkeys immunized with multiple F and G protein-based vaccines and assessed protection against the Memphis 37 strain of respiratory syncytial virus (RSV).
  
  
  METHODS
  Monkeys were immunized with F and G proteins adjuvanted with immunostimulatory (CpG) oligodeoxyribonucleotides admixed with either Alhydrogel or ISCOMATRIX adjuvant. Delivery of F and G proteins via replication incompetent recombinant vesicular stomatitis viruses (VSVs) and human adenoviruses was also evaluated. Mucosally or parenterally administered recombinant adenoviruses were used in prime-boost regimens with adjuvanted proteins or recombinant DNA.
  
  
  RESULTS
  Animals primed by intranasal delivery of recombinant adenoviruses, and boosted by intramuscular injection of adjuvanted F and G proteins, developed neutralizing antibodies and F/G protein-specific T cells and were protected from RSV infection. Intramuscular injections of Alhydrogel (plus CpG) adjuvanted F and G proteins reduced peak viral loads in the lungs of challenged monkeys. Granulocyte numbers were not significantly elevated, relative to controls, in postchallenge bronchoalveolar lavage samples from vaccinated animals.
  
  
  CONCLUSIONS
  This study has validated the use of RSV (Memphis 37) in an African green monkey model of intranasal infection and identified nonreplicating vaccines capable of eliciting protection in this higher species challenge model.
authors.affiliation: Pfizer Vaccine Research, La Jolla, California, USA. jimeyles@pfizer.com
authors.forename: Jim E
authors.initials: JE
authors.lastname: Eyles
authors.forename: J Erik
authors.initials: JE
authors.lastname: Johnson
authors.forename: Shakuntala
authors.initials: S
authors.lastname: Megati
authors.forename: Vidia
authors.initials: V
authors.lastname: Roopchand
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Cockle
authors.forename: Risini
authors.initials: R
authors.lastname: Weeratna
authors.forename: Shawn
authors.initials: S
authors.lastname: Makinen
authors.forename: Tom P
authors.initials: TP
authors.lastname: Brown
authors.forename: Susanne
authors.initials: S
authors.lastname: Lang
authors.forename: Susan E
authors.initials: SE
authors.lastname: Witko
authors.forename: Cheryl S
authors.initials: CS
authors.lastname: Kotash
authors.forename: Julia
authors.initials: J
authors.lastname: Li
authors.forename: Kate
authors.initials: K
authors.lastname: West
authors.forename: Oscar
authors.initials: O
authors.lastname: Maldonado
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Falconer
authors.forename: Clare
authors.initials: C
authors.lastname: Lees
authors.forename: George J
authors.initials: GJ
authors.lastname: Smith
authors.forename: Phil
authors.initials: P
authors.lastname: White
authors.forename: Paul
authors.initials: P
authors.lastname: Wright
authors.forename: Peter T
authors.initials: PT
authors.lastname: Loudon
authors.forename: James R
authors.initials: JR
authors.lastname: Merson
authors.forename: Kathrin U
authors.initials: KU
authors.lastname: Jansen
authors.forename: Maninder K
authors.initials: MK
authors.lastname: Sidhu
mesh_terms: D000260:Adenoviruses, Human / Q000235:genetics / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D018893:Bronchoalveolar Lavage / Q000379:methods; D002522:Chlorocebus aethiops; D006098:Granulocytes / Q000276:immunology / Q000821:virology; D007114:Immunization / Q000379:methods; D008168:Lung / Q000276:immunology / Q000821:virology; D011897:Random Allocation; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D022261:Respiratory Syncytial Virus Vaccines / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D012136:Respiratory Syncytial Viruses / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D018116:Vesiculovirus / Q000235:genetics / Q000276:immunology; D014760:Viral Fusion Proteins / Q000235:genetics / Q000276:immunology; D019562:Viral Load / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology; D014779:Virus Replication / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D022261:Respiratory Syncytial Virus Vaccines; D014760:Viral Fusion Proteins; D014764:Viral Proteins
keywords: CpG; adaptive immunity; adjuvant; immunization; intranasal; mucosal; nonhuman primate; pathogen; translational; viral vector