title: Effects of formalin-inactivated respiratory syncytial virus (FI-RSV) in the perinatal lamb model of RSV.
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.
authors: Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, Iowa, United States of America.
authors: Rachel J
authors: RJ
authors: Derscheid
authors: Jack M
authors: JM
authors: Gallup
authors: Cory J
authors: CJ
authors: Knudson
authors: Steven M
authors: SM
authors: Varga
authors: Drew D
authors: DD
authors: Grosz
authors: Albert
authors: A
authors: van Geelen
authors: Shannon J
authors: SJ
authors: Hostetter
authors: Mark R
authors: MR
authors: Ackermann
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000956:Antigens, Viral / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000821:virology; D004195:Disease Models, Animal; D005557:Formaldehyde / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000821:virology; D009500:Neutralization Tests; D010950:Plasma Cells / Q000187:drug effects / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D018357:Respiratory Syncytial Virus Infections / Q000473:pathology / Q000821:virology*; D012136:Respiratory Syncytial Viruses / Q000187:drug effects / Q000502:physiology*; D034561:Sheep, Domestic / Q000821:virology*; D014611:Vaccination; D038301:Virus Inactivation / Q000187:drug effects*
chemical_list: D000956:Antigens, Viral; D012367:RNA, Viral; D005557:Formaldehyde