title: Evaluation of attenuation, immunogenicity and efficacy of a bovine parainfluenza virus type 3 (PIV-3) vaccine and a recombinant chimeric bovine/human PIV-3 vaccine vector in rhesus monkeys.
abstract: Restricted replication in the respiratory tract of rhesus monkeys is an intrinsic property of bovine parainfluenza virus type 3 (bPIV-3) strains. This host range phenotype of bPIV-3 has been utilized as a marker to evaluate the attenuation of bPIV-3 vaccines for human use. Two safety, immunogenicity and efficacy studies in primates evaluated and compared three human parainfluenza virus type 3 (hPIV-3) vaccine candidates: biologically derived bPIV-3, a plasmid-derived bPIV-3 (r-bPIV-3) and a chimeric bovine/human PIV-3 (b/hPIV-3). These studies also examined the feasibility of substituting Vero cells, cultured in the presence or absence of foetal bovine serum, for foetal rhesus lung-2 (FRhL-2) cells as the tissue culture substrate for the production of bPIV-3 vaccine. The results demonstrated that (i) Vero cell-produced bPIV-3 was as attenuated, immunogenic and efficacious as bPIV-3 vaccine grown in FRhL-2 cells, (ii) plasmid-derived bPIV-3 was as attenuated, immunogenic and efficacious as the biologically derived bPIV-3 and (iii) the b/hPIV-3 chimera displayed an intermediate attenuation phenotype and protected animals completely from hPIV-3 challenge. These results support the use of bPIV-3 vaccines propagated in Vero cells in human clinical trials and the use of b/hPIV-3 as a virus vaccine vector to express foreign viral antigens.
authors.affiliation: MedImmune Vaccines Inc., 297 North Bernardo Avenue, Mountain View, CA 94043, USA.
authors.forename: Sridhar
authors.initials: S
authors.lastname: Pennathur
authors.affiliation: MedImmune Vaccines Inc., 297 North Bernardo Avenue, Mountain View, CA 94043, USA.
authors.forename: Aurelia A
authors.initials: AA
authors.lastname: Haller
authors.affiliation: MedImmune Vaccines Inc., 297 North Bernardo Avenue, Mountain View, CA 94043, USA.
authors.forename: Mia
authors.initials: M
authors.lastname: MacPhail
authors.affiliation: MedImmune Vaccines Inc., 297 North Bernardo Avenue, Mountain View, CA 94043, USA.
authors.forename: Tom
authors.initials: T
authors.lastname: Rizzi
authors.affiliation: MedImmune Vaccines Inc., 297 North Bernardo Avenue, Mountain View, CA 94043, USA.
authors.forename: Sepideh
authors.initials: S
authors.lastname: Kaderi
authors.affiliation: MedImmune Vaccines Inc., 297 North Bernardo Avenue, Mountain View, CA 94043, USA.
authors.forename: Fiona
authors.initials: F
authors.lastname: Fernandes
authors.affiliation: MedImmune Vaccines Inc., 297 North Bernardo Avenue, Mountain View, CA 94043, USA.
authors.forename: Leenas
authors.initials: L
authors.lastname: Bicha
authors.affiliation: MedImmune Vaccines Inc., 297 North Bernardo Avenue, Mountain View, CA 94043, USA.
authors.forename: Jeanne H
authors.initials: JH
authors.lastname: Schickli
authors.affiliation: MedImmune Vaccines Inc., 297 North Bernardo Avenue, Mountain View, CA 94043, USA.
authors.forename: Roderick S
authors.initials: RS
authors.lastname: Tang
authors.affiliation: MedImmune Vaccines Inc., 297 North Bernardo Avenue, Mountain View, CA 94043, USA.
authors.forename: Wendy
authors.initials: W
authors.lastname: Chen
authors.affiliation: MedImmune Vaccines Inc., 297 North Bernardo Avenue, Mountain View, CA 94043, USA.
authors.forename: Nick
authors.initials: N
authors.lastname: Nguyen
authors.affiliation: MedImmune Vaccines Inc., 297 North Bernardo Avenue, Mountain View, CA 94043, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Mathie
authors.affiliation: MedImmune Vaccines Inc., 297 North Bernardo Avenue, Mountain View, CA 94043, USA.
authors.forename: Hersh
authors.initials: H
authors.lastname: Mehta
authors.affiliation: MedImmune Vaccines Inc., 297 North Bernardo Avenue, Mountain View, CA 94043, USA.
authors.forename: Kathleen L
authors.initials: KL
authors.lastname: Coelingh
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005822:Genetic Vectors; D007117:Immunization, Secondary; D007070:Immunoglobulin A / Q000097:blood; D008253:Macaca mulatta; D009500:Neutralization Tests; D022241:Parainfluenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D029101:Parainfluenza Virus 3, Bovine / Q000235:genetics / Q000276:immunology*; D010224:Parainfluenza Virus 3, Human / Q000235:genetics / Q000276:immunology*; D018184:Paramyxoviridae Infections / Q000097:blood / Q000276:immunology* / Q000517:prevention & control*; D010957:Plasmids; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D014709:Vero Cells
chemical_list: D000914:Antibodies, Viral; D007070:Immunoglobulin A; D022241:Parainfluenza Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic