Implication of respiratory syncytial virus (RSV) F transgene sequence heterogeneity observed in Phase 1 evaluation of MEDI-534, a live attenuated parainfluenza type 3 vectored RSV vaccine

• Published in: Vaccine Vol. 31; no. 26; pp. 2822 - 2827
• Main Authors: Yang, Chin-Fen, Wang, C. Kathy, Malkin, Elissa, Schickli, Jeanne H, Shambaugh, Cindy, Zuo, Fengrong, Galinski, Mark S, Dubovsky, Filip, Tang, Roderick S
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 10-06-2013; Elsevier; Elsevier Limited
• Subjects: Age; Allergy and Immunology; Animals; Antibodies, Viral - blood; Applied microbiology; Biological and medical sciences; Bovine parainfluenza virus 3; Cattle; children; Cohort Studies; Deoxyribonucleic acid; DNA; fluorescent antibody technique; Fundamental and applied biological sciences. Psychology; Glycoproteins; Heterogeneity; Humans; Immunization; Immunogenicity; Infant; Microbiology; nose; nucleotides; open reading frames; Parainfluenza virus; Parainfluenza Virus 3, Bovine - genetics; Parainfluenza Virus 3, Bovine - immunology; Parainfluenza Virus 3, Human - genetics; Parainfluenza Virus 3, Human - immunology; Polymerase chain reaction; Proteins; Respiratory syncytial virus; Respiratory syncytial virus (RSV); Respiratory Syncytial Virus Infections - immunology; Respiratory Syncytial Virus Infections - prevention & control; Respiratory Syncytial Viruses - genetics; Respiratory Syncytial Viruses - immunology; RSV F expression; Sequence Analysis, DNA; stop codon; Subpopulations; Transgenes; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Attenuated - genetics; Vaccines, Attenuated - immunology; Viral Vaccines - genetics; Viral Vaccines - immunology; Virus Shedding; Virus variants; viruses; Virus variants; Respiratory syncytial virus (RSV); RSV F expression; Immunogenicity; Human; Retroviridae; Vaccine; Virus; Human syncytial virus; Spumavirus; Phase I trial; Attenuated strain; Child; Vector
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2013.04.006

Highlights • The live RSV vaccine virus was primarily detected in young children post dose 1. • About half of the shed vaccine viruses (13/24) contained sequence changes. • These sequence changes may result in lower RSVF protein expression. • These changes may have been selected during replication in humans. • The presence of vaccine variants may be associated with lower RSVF sero-responses.