title: Development of a PIV-vectored RSV vaccine: preclinical evaluation of safety, toxicity, and enhanced disease and initial clinical testing in healthy adults.
abstract: MEDI-534 is a bivalent live attenuated vaccine candidate against human respiratory syncytial virus (hRSV) and human parainfluenza virus type 3 (hPIV3) that was previously shown to be immunogenic and to protect rodents and African green monkeys from wild-type (wt) hRSV challenge. We performed further preclinical evaluations to address the safety of MEDI-534 prior to human testing. MEDI-534 did not predispose rodents to enhanced RSV disease following wt-RSV challenge, and the tissue tropism of the chimeric virus was confined to the respiratory tract. Representative clinical trial material did not produce toxicity in rats. In adults, MEDI-534 was highly restricted in replication, did not boost RSV and PIV3 antibody titers, and produced no medically significant vaccine-related adverse events thereby warranting further evaluation in pediatric populations.
authors.affiliation: MedImmune, 297 North Bernardo Avenue, Mountain View, CA 94043, USA. tangr@medimmune.com
authors.forename: Roderick S
authors.initials: RS
authors.lastname: Tang
authors.forename: Richard R
authors.initials: RR
authors.lastname: Spaete
authors.forename: Mark W
authors.initials: MW
authors.lastname: Thompson
authors.forename: Mia
authors.initials: M
authors.lastname: MacPhail
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Guzzetta
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Ryan
authors.forename: Keith
authors.initials: K
authors.lastname: Reisinger
authors.forename: Patricia
authors.initials: P
authors.lastname: Chandler
authors.forename: Milo
authors.initials: M
authors.lastname: Hilty
authors.forename: Robert E
authors.initials: RE
authors.lastname: Walker
authors.forename: Margarita M
authors.initials: MM
authors.lastname: Gomez
authors.forename: Genevieve A
authors.initials: GA
authors.lastname: Losonsky
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002522:Chlorocebus aethiops; D006224:Cricetinae; D004195:Disease Models, Animal; D004311:Double-Blind Method; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D008297:Male; D022241:Parainfluenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D010224:Parainfluenza Virus 3, Human / Q000235:genetics / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D022261:Respiratory Syncytial Virus Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology; D010253:Respirovirus Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D016205:Sigmodontinae; D016896:Treatment Outcome; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014709:Vero Cells; D055815:Young Adult
chemical_list: D022241:Parainfluenza Vaccines; D022261:Respiratory Syncytial Virus Vaccines; D014613:Vaccines, Attenuated