Development of a PIV-vectored RSV vaccine: Preclinical evaluation of safety, toxicity, and enhanced disease and initial clinical testing in healthy adults

• Published in: Vaccine 2008-11, Vol.26 (50), p.6373-6382
• Main Authors: Tang, Roderick S, Spaete, Richard R, Thompson, Mark W, MacPhail, Mia, Guzzetta, Jeanne M, Ryan, Patricia C, Reisinger, Keith, Chandler, Patricia, Hilty, Milo, Walker, Robert E, Gomez, Margarita M, Losonsky, Genevieve A
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Allergy and Immunology; Animals; Applied microbiology; Biological and medical sciences; Cercopithecus aethiops; Cotton; Cricetinae; Disease Models, Animal; Double-Blind Method; FDA approval; Female; Fundamental and applied biological sciences. Psychology; Genetic Vectors; Health care; Histology; Human respiratory syncytial virus; Humans; Infections; Male; Microbiology; Parainfluenza Vaccines - administration & dosage; Parainfluenza Vaccines - genetics; Parainfluenza Vaccines - immunology; Parainfluenza virus; Parainfluenza Virus 3, Human - genetics; Parainfluenza Virus 3, Human - immunology; PIV3; Potassium; Proteins; Rats; Rats, Sprague-Dawley; Reproductive system; Respiratory syncytial virus; Respiratory Syncytial Virus Infections - immunology; Respiratory Syncytial Virus Infections - prevention & control; Respiratory Syncytial Virus Infections - virology; Respiratory Syncytial Virus Vaccines - administration & dosage; Respiratory Syncytial Virus Vaccines - adverse effects; Respiratory Syncytial Virus Vaccines - immunology; Respiratory Syncytial Virus, Human - immunology; Respiratory tract; Respirovirus Infections - immunology; Respirovirus Infections - prevention & control; Respirovirus Infections - virology; Rodents; RSV; Sigmodontinae; Toxicity; Treatment Outcome; Vaccine; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Attenuated - administration & dosage; Vaccines, Attenuated - adverse effects; Vaccines, Attenuated - immunology; Vero Cells; Viral infections; Young Adult
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2008.09.018

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.