title: Live-attenuated intranasal parainfluenza virus type 2 vaccine candidates developed by reverse genetics containing L polymerase protein mutations imported from heterologous paramyxoviruses.
abstract: Live-attenuated recombinant human parainfluenza virus type 2 (rHPIV2) vaccine candidates were created using reverse genetics by importing known attenuating mutations in the L polymerase protein from heterologous paramyxoviruses into the homologous sites of the HPIV2 L protein. Four recombinants (rF460L, rY948H, rL1566I, and rS1724I) were recovered and three were attenuated for replication in hamsters. The genetic stability of the imported mutations at three of the four sites was enhanced by use of alternative codons or by deletion of a pair of amino acids. rHPIV2s bearing these modified mutations exhibited enhanced attenuation. The genetically stabilized mutations conferring a high level of attenuation will be useful in generating a live-attenuated virus vaccine for HPIV2.
authors.affiliation: Laboratory of Infectious Diseases, Respiratory Viruses Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 50 South Drive, Building 50, Room 6509, MSC 8007, Bethesda, MD 20892, USA. snolan@niaid.nih.gov
authors.forename: Sheila M
authors.initials: SM
authors.lastname: Nolan
authors.forename: Sonja R
authors.initials: SR
authors.lastname: Surman
authors.forename: Emerito
authors.initials: E
authors.lastname: Amaro-Carambot
authors.forename: Peter L
authors.initials: PL
authors.lastname: Collins
authors.forename: Brian R
authors.initials: BR
authors.lastname: Murphy
authors.forename: Mario H
authors.initials: MH
authors.lastname: Skiadopoulos
mesh_terms: D000281:Administration, Intranasal; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003062:Codon; D006224:Cricetinae; D012321:DNA-Directed RNA Polymerases / Q000235:genetics*; D006801:Humans; D008647:Mesocricetus; D008969:Molecular Sequence Data; D009154:Mutation; D022241:Parainfluenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D010223:Parainfluenza Virus 2, Human / Q000276:immunology* / Q000502:physiology; D018098:Paramyxovirinae / Q000235:genetics*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology*; D014779:Virus Replication
chemical_list: D003062:Codon; D022241:Parainfluenza Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D012321:DNA-Directed RNA Polymerases