Bovine Model of Respiratory Syncytial Virus Infection

Taylor, Geraldine

doi:10.1007/978-3-642-38919-1_16

Cited by 24 publications

(30 citation statements)

References 58 publications

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“…The cell tropism of clinical RSV strains may play a role in their differential pathogenesis. RSV has been shown to infect cells in both the bronchial and bronchiolar epithelia and alveolar cells in the lungs of RSV-infected children and mice (53,54). RSV 2-20 viral antigen is localized to the airway epithelium at greater levels than A2 antigen at day 1 postinfection (13).…”

Section: Discussionmentioning

confidence: 99%

The Respiratory Syncytial Virus Fusion Protein and Neutrophils Mediate the Airway Mucin Response to Pathogenic Respiratory Syncytial Virus Infection

Stokes

Currier

Sakamoto

et al. 2013

J Virol

108

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dRespiratory syncytial virus (RSV) is the leading cause of death due to a viral etiology in infants. RSV disease is characterized by epithelial desquamation, neutrophilic bronchiolitis and pneumonia, and obstructive pulmonary mucus. It has been shown that infection of BALB/cJ mice with RSV clinical isolate A2001/2-20 (2-20) results in a higher early viral load, greater airway necrosis, and higher levels of interleukin-13 (IL-13) and airway mucin expression than infection with RSV laboratory strain A2. We hypothesized that the fusion (F) protein of RSV 2-20 is a mucus-inducing viral factor. In vitro, the fusion activity of 2-20 F but not that of A2 F was enhanced by expression of RSV G. We generated a recombinant F-chimeric RSV by replacing the F gene of A2 with the F gene of 2-20, generating A2-2-20F. Similar to the results obtained with the parent 2-20 strain, infection of BALB/cJ mice with A2-2-20F resulted in a higher early viral load and higher levels of subsequent pulmonary mucin expression than infection with the A2 strain. A2-2-20F infection induced greater necrotic airway damage and neutrophil infiltration than A2 infection. We hypothesized that the neutrophil response to A2-2-20F infection is involved in mucin expression. Antibody-mediated depletion of neutrophils in RSV-infected mice resulted in lower tumor necrosis factor alpha levels, fewer IL-13-expressing CD4 T cells, and less airway mucin production in the lung. Our data are consistent with a model in which the F and attachment (G) glycoprotein functional interaction leads to enhanced fusion and F is a key factor in airway epithelium infection, pathogenesis, and subsequent airway mucin expression.

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Section: Discussionmentioning

confidence: 99%

The Respiratory Syncytial Virus Fusion Protein and Neutrophils Mediate the Airway Mucin Response to Pathogenic Respiratory Syncytial Virus Infection

Stokes

Currier

Sakamoto

et al. 2013

J Virol

108

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“…Studies of dendritic cells in the lungs of human infants is hampered by both ethical and technical hurdles. While there are several animal models used to study RSV[19-22], none completely recapitulate disease pathogenesis in infants. Additionally, most studies focus on infection of adult animals, which does not address the unique context of the infant respiratory tract and immune system.…”

Section: Introductionmentioning

confidence: 99%

Determinants of early life immune responses to RSV infection

Ruckwardt

Morabito

Graham

2016

Current Opinion in Virology

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Respiratory syncytial virus causes significant morbidity and mortality in both developed and developing countries, and a vaccine that adequately protects from severe disease remains an important unmet need. RSV disease has an inordinate impact on the very young, and the physical and immunological immaturity of early life complicates vaccine design. Defining and targeting the functional capacities of early life immune responses and controlling responses during primary antigen exposure with selected vaccine delivery approaches will be important for protecting infants by active immunization. Alternatively, vaccination of older children and pregnant mothers may ameliorate disease burden indirectly until infants reach about six months of age,when they can generate more effective anti-RSV immune responses.

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“…Calves are the natural hosts of BRSV, and the pathogenesis and epidemiology of BRSV infection in calves are similar to those in children (10). Furthermore, ERD has been observed after a natural BRSV infection in calves that had been vaccinated with an inactivated BRSV vaccine, and has been reproduced experimentally in calves vaccinated with FI-BRSV (11)(12)(13), although this has not been consistently reproducible (30).…”

Section: Discussionmentioning

confidence: 95%

Efficacy of a virus-vectored vaccine against human and bovine respiratory syncytial virus infections

Taylor

Thom

Capone³

et al. 2015

Sci. Transl. Med.

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Human respiratory syncytial virus (HRSV) is a major cause of lower respiratory tract disease in children and the elderly for which there is still no effective vaccine. We have previously shown that PanAd3-RSV, which is a chimpanzee adenovirus-vectored vaccine candidate that expresses a secreted form of the HRSV F protein together with the N and M2-1 proteins of HRSV, is immunogenic in rodents and nonhuman primates, and protects mice and cotton rats from HRSV challenge. Because the extent to which protection demonstrated in rodent models will translate to humans is unclear, we have exploited the calf model of bovine RSV (BRSV) infection, which mimics HRSV disease in children more closely than do experimental models of unnatural laboratory hosts, to evaluate the safety and efficacy of the PanAd3-RSV vaccine. We show that PanAd3-RSV alone and in combination with a modified vaccinia Ankara expressing the same HRSV antigens (MVA-RSV) induced neutralizing antibodies and cellular immunity in young seronegative calves and protected against upper and lower respiratory tract infection and pulmonary disease induced by heterologous BRSV challenge. There was no evidence either of enhanced pulmonary pathology or of enhanced respiratory disease in vaccinated calves after BRSV challenge. These findings support the continued evaluation of the vectored RSV vaccines in man.

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Bovine Model of Respiratory Syncytial Virus Infection

Cited by 24 publications

References 58 publications

The Respiratory Syncytial Virus Fusion Protein and Neutrophils Mediate the Airway Mucin Response to Pathogenic Respiratory Syncytial Virus Infection

The Respiratory Syncytial Virus Fusion Protein and Neutrophils Mediate the Airway Mucin Response to Pathogenic Respiratory Syncytial Virus Infection

Determinants of early life immune responses to RSV infection

Efficacy of a virus-vectored vaccine against human and bovine respiratory syncytial virus infections

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