title: The recombinant chimeric human parainfluenza virus type 1 vaccine candidate, rHPIV3-1cp45, is attenuated, immunogenic, and protective in African green monkeys.
abstract: A recombinant live-attenuated chimeric human parainfluenza virus type 1 (HPIV1) candidate vaccine was previously generated by replacing the fusion (F) and hemagglutinin-neuraminidase (HN) glycoprotein open reading frames (ORFs) of the HPIV3 candidate vaccine, rHPIV3cp45, with those of wild-type HPIV1. Previously, this recombinant chimeric virus, designated rHPIV3-1cp45, exhibited a greater level of the temperature sensitivity of replication in vitro and a greater level of attenuation of replication in the respiratory tract of immunized hamsters when compared to its HPIV3cp45 parent virus. In the present study, rHPIV3-1cp45 was evaluated for its level of attenuation and efficacy in African green monkeys (Cercopithecus aethiops), a primate in which both HPIV1 and HPIV3 wild-type viruses replicate efficiently. The rHPIV3-1cp45 candidate vaccine was as restricted in replication in the upper and lower respiratory tract as its thoroughly characterized rHPIV3cp45 parent indicating that the attenuating mutations present in the rHPIV3cp45 backbone specified an appropriate level of attenuation of rHPIV3-1cp45 for primates. The level to which rHPIV3-1cp45 replicated in the respiratory tract of African green monkeys was also sufficient to induce a strong immune response to HPIV1 and provided protection against challenge with wild-type HPIV1. These results provide a basis for further evaluation of this HPIV1 candidate vaccine in humans.
authors.affiliation: Respiratory Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. mskiadopoulos@niaid.nih.gov
authors.forename: Mario H
authors.initials: MH
authors.lastname: Skiadopoulos
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Tatem
authors.forename: Sonja R
authors.initials: SR
authors.lastname: Surman
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Mitcho
authors.forename: Shin Lu
authors.initials: SL
authors.lastname: Wu
authors.forename: William R
authors.initials: WR
authors.lastname: Elkins
authors.forename: Brian R
authors.initials: BR
authors.lastname: Murphy
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D002678:Chimera / Q000235:genetics / Q000276:immunology; D002522:Chlorocebus aethiops; D006801:Humans; D009154:Mutation; D022241:Parainfluenza Vaccines / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D010222:Parainfluenza Virus 1, Human / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D010253:Respirovirus Infections / Q000276:immunology / Q000517:prevention & control; D013696:Temperature; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D014779:Virus Replication
chemical_list: D000914:Antibodies, Viral; D022241:Parainfluenza Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic