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 Vol. 26; no. 50; pp. 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: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 25.11.2008; Elsevier; Elsevier Limited
• 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; RSV; Vaccine; PIV3; Toxicity; Vector
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2008.09.018

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.