A Single-Dose Recombinant Parainfluenza Virus 5-Vectored Vaccine Expressing Respiratory Syncytial Virus (RSV) F or G Protein Protected Cotton Rats and African Green Monkeys from RSV Challenge
| Autor: | Amy S. Espeseth, Gwendolyn J. Heidecker, Lani Indrawati, Xiaoping Liang, Dhanasekaran Govindarajan, Michael P. Citron, Cheryl Callahan, Biao He, Shannon Phan, Daniel J. DiStefano, Sheri Dubey, Dai Wang |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
viruses Immunology Genetic Vectors Respiratory Syncytial Virus Infections medicine.disease_cause Antibodies Viral Microbiology Virus 03 medical and health sciences Viral Envelope Proteins Virology Vaccines and Antiviral Agents Chlorocebus aethiops medicine Respiratory Syncytial Virus Vaccines Animals Cotton rat Sigmodontinae Lung Vero Cells Vaccines Synthetic biology Immunogenicity Vaccination Antibody titer virus diseases respiratory system biology.organism_classification Rats Disease Models Animal 030104 developmental biology Respiratory syncytial virus (RSV) Immunization Insect Science Respiratory Syncytial Virus Human biology.protein Parainfluenza Virus 5 African Green Monkey Antibody Viral Fusion Proteins |
| Popis: | Human respiratory syncytial virus (RSV) is a common cause of severe respiratory disease among infants, immunocompromised individuals, and the elderly. No licensed vaccine is currently available. In this study, we evaluated two parainfluenza virus 5 (PIV5)-vectored vaccines expressing RSV F (PIV5/F) or G (PIV5/G) protein in the cotton rat and African green monkey models for their replication, immunogenicity, and efficacy of protection against RSV challenge. Following a single intranasal inoculation, both animal species shed the vaccine viruses for a limited time but without noticeable clinical symptoms. In cotton rats, the vaccines elicited RSV F- or G-specific serum antibodies and conferred complete lung protection against RSV challenge at doses as low as 10 3 PFU. Neither vaccine produced the enhanced lung pathology observed in animals immunized with formalin-inactivated RSV. In African green monkeys, vaccine-induced serum and mucosal antibody responses were readily detected, as well. PIV5/F provided nearly complete protection against RSV infection in the upper and lower respiratory tract at a dose of 10 6 PFU of vaccine. At the same dose levels, PIV5/G was less efficacious. Both PIV5/F and PIV5/G were also able to boost neutralization titers in RSV-preexposed African green monkeys. Overall, our data indicated that PIV5/F is a promising RSV vaccine candidate. IMPORTANCE A safe and efficacious respiratory syncytial virus (RSV) vaccine remains elusive. We tested the recombinant parainfluenza virus 5 (PIV5) vectors expressing RSV glycoproteins for their immunogenicity and protective efficacy in cotton rats and African green monkeys, which are among the best available animal models to study RSV infection. In both species, a single dose of intranasal immunization with PIV5-vectored vaccines was able to produce systemic and local immunity and to protect animals from RSV challenge. The vaccines could also boost RSV neutralization antibody titers in African green monkeys that had been infected previously. Our data suggest that PIV5-vectored vaccines could potentially protect both the pediatric and elderly populations and support continued development of the vector platform. |
| Databáze: | OpenAIRE |
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