title: Increased replication of respiratory syncytial virus (RSV) in pulmonary infiltrates is associated with enhanced histopathological disease in bonnet monkeys (Macaca radiata) pre-immunized with a formalin-inactivated RSV vaccine.
abstract: The pathology of respiratory syncytial virus (RSV) disease in bonnet monkeys parallels findings with human RSV disease. RSV-infected animals pre-immunized with a formalin-inactivated (FI) RSV vaccine develop inflammation in peribronchiolar, perivascular, interstitial and intra-alveolar sites with lung inflammation scores significantly higher than animals with a primary RSV infection and those pre-immunized with an FI-Vero cell control vaccine (P=0.05). Animals previously infected and re-exposed to RSV had significantly lower alveolar, interstitial and total lung inflammation scores than in primary infection (P=0.05). Immunization with two intra-muscular doses of 0.5 ml of the FI-RSV vaccine administered 21 days apart resulted in little serum-neutralizing and ELISA antibody, low levels of secretory IgA and a low lymphocyte proliferative response that was significantly lower than the response observed in animals that were previously infected with live RSV. Higher RSV virus titres were detected in the lungs and lung lavage fluid of monkeys immunized with the FI-RSV vaccine than in those with a primary infection (P=0.001). RSV was detected by in situ hybridization in pulmonary inflammatory infiltrates, where the single most abundant infiltrating cellular species was macrophages, so it may be these cells that support the enhanced virus replication that contributes to the enhanced pulmonary pathology of FI-RSV immunization.
authors.affiliation: Department of Pediatrics, Box B140, Section of Infectious Diseases1, Department of Pediatrics and Immunology2, University of Colorado Health Sciences Center, 4200 East 9th Avenue, Denver, CO 80262, USA.
authors.forename: Esther M
authors.initials: EM
authors.lastname: Ponnuraj
authors.affiliation: Department of Pediatrics, Box B140, Section of Infectious Diseases1, Department of Pediatrics and Immunology2, University of Colorado Health Sciences Center, 4200 East 9th Avenue, Denver, CO 80262, USA.
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Hayward
authors.affiliation: Department of Virology and Immunology, Christian Medical College Hospital, Vellore, 632004, India3.
authors.forename: Anthony
authors.initials: A
authors.lastname: Raj
authors.affiliation: Department of Pathology, Providence Memorial Hospital, El Paso, TX 79902, USA4.
authors.forename: Harry
authors.initials: H
authors.lastname: Wilson
authors.affiliation: Department of Pediatrics, Box B140, Section of Infectious Diseases1, Department of Pediatrics and Immunology2, University of Colorado Health Sciences Center, 4200 East 9th Avenue, Denver, CO 80262, USA.
authors.forename: Eric A F
authors.initials: EAF
authors.lastname: Simoes
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005557:Formaldehyde / Q000494:pharmacology; D006801:Humans; D007249:Inflammation; D008168:Lung / Q000276:immunology / Q000473:pathology* / Q000821:virology; D008255:Macaca radiata; D018357:Respiratory Syncytial Virus Infections / Q000473:pathology* / Q000517:prevention & control / Q000821:virology*; D022261:Respiratory Syncytial Virus Vaccines / Q000276:immunology*; D018113:Respiratory Syncytial Virus, Human / Q000187:drug effects / Q000502:physiology*; D014611:Vaccination; D015164:Vaccines, Inactivated / Q000276:immunology; D014779:Virus Replication
chemical_list: D022261:Respiratory Syncytial Virus Vaccines; D015164:Vaccines, Inactivated; D005557:Formaldehyde