Effects of formalin-inactivated respiratory syncytial virus (FI-RSV) in the perinatal lamb model of RSV

Rachel J Derscheid; Jack M Gallup; Cory J Knudson; Steven M Varga; Drew D Grosz; Albert van Geelen; Shannon J Hostetter; Mark R Ackermann

doi:10.1371/journal.pone.0081472

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Effects of formalin-inactivated respiratory syncytial virus (FI-RSV) in the perinatal lamb model of RSV

Journal article

Open access

Peer reviewed

Effects of formalin-inactivated respiratory syncytial virus (FI-RSV) in the perinatal lamb model of RSV

Rachel J Derscheid, Jack M Gallup, Cory J Knudson, Steven M Varga, Drew D Grosz, Albert van Geelen, Shannon J Hostetter and Mark R Ackermann

PloS one, Vol.8(12), pp.e81472-e81472

2013

DOI: 10.1371/journal.pone.0081472

PMCID: PMC3855688

PMID: 24324695

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Abstract

Respiratory syncytial virus (RSV) is the most frequent cause of bronchiolitis in infants and children worldwide. There are currently no licensed vaccines or effective antivirals. The lack of a vaccine is partly due to increased caution following the aftermath of a failed clinical trial of a formalin-inactivated RSV vaccine (FI-RSV) conducted in the 1960's that led to enhanced disease, necessitating hospitalization of 80% of vaccine recipients and resulting in two fatalities. Perinatal lamb lungs are similar in size, structure and physiology to those of human infants and are susceptible to human strains of RSV that induce similar lesions as those observed in infected human infants. We sought to determine if perinatal lambs immunized with FI-RSV would develop key features of vaccine-enhanced disease. This was tested in colostrum-deprived lambs immunized at 3-5 days of age with FI-RSV followed two weeks later by RSV infection. The FI-RSV-vaccinated lambs exhibited several key features of RSV vaccine-enhanced disease, including reduced RSV titers in bronchoalveolar lavage fluid and lung, and increased infiltration of peribronchiolar and perivascular lymphocytes compared to lambs either undergoing an acute RSV infection or naïve controls; all features of RSV vaccine-enhanced disease. These results represent a first step proof-of-principle demonstration that the lamb can develop altered responses to RSV following FI-RSV vaccination. The lamb model may be useful for future mechanistic studies as well as the assessment of RSV vaccines designed for infants.

Animals, Newborn

Immunohistochemistry

Lung - pathology

Antigens, Viral - metabolism

Bronchoalveolar Lavage Fluid - virology

Respiratory Syncytial Viruses - physiology

Respiratory Syncytial Viruses - drug effects

Humans

Vaccination

Sheep, Domestic - virology

Formaldehyde - pharmacology

Neutralization Tests

Virus Inactivation - drug effects

Plasma Cells - drug effects

Lung - virology

Animals

Lung - drug effects

Plasma Cells - metabolism

RNA, Viral - metabolism

Respiratory Syncytial Virus Infections - pathology

Respiratory Syncytial Virus Infections - virology

Disease Models, Animal

Details

Title: Subtitle: Effects of formalin-inactivated respiratory syncytial virus (FI-RSV) in the perinatal lamb model of RSV
Creators: Rachel J Derscheid - Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, Iowa, United States of America
Jack M Gallup
Cory J Knudson
Steven M Varga
Drew D Grosz
Albert van Geelen
Shannon J Hostetter
Mark R Ackermann
Resource Type: Journal article
Publication Details: PloS one, Vol.8(12), pp.e81472-e81472
DOI: 10.1371/journal.pone.0081472
PMID: 24324695
PMCID: PMC3855688
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science
Grant note: R56AI09100 / NIAID NIH HHS T32 AI007485 / NIAID NIH HHS
Language: English
Date published: 2013
Academic Unit: Graduate College Admin and Gen; Microbiology and Immunology; Pathology
Record Identifier: 9984083275802771

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