A bovine model of vaccine enhanced respiratory syncytial virus pathophysiology

Gershwin, Laurel J.; Schelegle, Edward S.; Gunther, Robert A.; Anderson, Margaret Lavinia; Woolums, Amelia R.; Larochelle, Danielle; Boyle, Gabrielle A.; Friebertshauser, Kathleen E.; Singer, Randall S.

doi:10.1016/s0264-410x(98)80123-0

Cited by 127 publications

(124 citation statements)

References 23 publications

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“…Although virus shedding has occasionally been detected upon experimental BRSV re-infection, little or no clinical disease is observed in reinfected animals [69,109,134,145]. Similar to observations made for HRSV [67], exacerbated clinical signs have been observed following a natural BRSV infection in animals immunised with inactivated vaccines [5, 47,119].…”

Section: Epidemiologymentioning

confidence: 89%

Bovine respiratory syncytial virus infection

Valarcher¹,

2007

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-Bovine respiratory syncytial virus (BRSV) belongs to the pneumovirus genus within the family Paramyxoviridae and is a major cause of respiratory disease in young calves. BRSV is enveloped and contains a negative sense, single-stranded RNA genome encoding 11 proteins. The virus replicates predominantly in ciliated respiratory epithelial cells but also in type II pneumocytes. It appears to cause little or no cytopathology in ciliated epithelial cell cultures in vitro, suggesting that much of the pathology is due to the host's response to virus infection. RSV infection induces an array of pro-inflammatory chemokines and cytokines that recruit neutrophils, macrophages and lymphocytes to the respiratory tract resulting in respiratory disease. Although the mechanisms responsible for induction of these chemokines and cytokines are unclear, studies on the closely related human (H)RSV suggest that activation of NF-κB via TLR4 and TLR3 signalling pathways is involved. An understanding of the mechanisms by which BRSV is able to establish infection and induce an inflammatory response has been facilitated by advances in reverse genetics, which have enabled manipulation of the virus genome. These studies have demonstrated an important role for the non-structural proteins in anti-interferon activity, a role for a virokinin, released during proteolytic cleavage of the fusion protein, in the inflammatory response and a role for the SH and the secreted form of the G protein in establishing pulmonary infection. Knowledge gained from these studies has also provided the opportunity to develop safe, stable, live attenuated virus vaccine candidates.

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Section: Epidemiologymentioning

confidence: 89%

Bovine respiratory syncytial virus infection

Valarcher¹,

2007

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“…In addition, RSV challenge of calves previously immunized with FI-RSV results in enhanced pulmonary disease in the presence of a Th2 response [66,67]. The use of recombinant vaccinia virus vaccines and DNA vaccines has been effective at reducing the development of disease in this natural host model [68,69].…”

Section: Concluding Remarks and Future Perspectivementioning

confidence: 99%

Overcoming T-Cell-Mediated Immunopathology to Achieve Safe Respiratory Syncytial Virus Vaccination

Castilow

Varga

2008

Future Virol.

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SummaryRespiratory syncytial virus (RSV) is the leading cause of lower respiratory tract disease in young children. Premature infants, immunocompromised individuals, and the elderly exhibit an increased risk for the development of severe disease after RSV infection. Currently, there is not a safe and effective RSV vaccine available, in part due to our incomplete understanding of how severe immunopathology was induced following RSV infection of children previously immunized with a formalin-inactivated RSV vaccine. Much of our current understanding of RSV vaccine-enhanced disease can be attributed to the establishment of multiple mouse models of RSV vaccination. Studies analyzing the RSV-specific immune response in mice have clearly demonstrated that both CD4 and CD8 memory T cells contribute to RSV-induced immunopathology. In this review we will focus our discussion on data generated from the mouse models of RSV immunization that have advanced our understanding of how virus-specific T cells mediate immunopathology and RSV vaccine-enhanced disease.

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“…This phenomenon was first observed in a human vaccine trial in the 1960s [4] and was later found to also occur in cattle immunized with formalin-or beta-propriolactone-inactivated bRSV [5,6]. Enhanced disease resulting from immunization with Fl-virus has an immunopathological basis and has now been modeled in hRSV-infected mice [2,[7][8][9] and monkeys [10] and in bRSV-infected cattle [1,[11][12][13]. In mice, immunization with inactivated virus evokes a Th-2 biased CD4 T cell response, which is associated with eosinophilia and clinical symptoms upon challenge [2].…”

Section: Introductionmentioning

confidence: 99%

Kinetics of antiviral CD8 T cell responses during primary and post-vaccination secondary bovine respiratory syncytial virus infection

Antonis

Claassen

Hensen

et al. 2006

Vaccine

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We have measured antiviral CD8 T cells responses in bovine respiratory syncytial virus (bRSV) infected calves that had been immunized with either formalin-inactivated (FI) or live-attenuated (L) bRSV, with evidence of immunopathology following challenge of calves vaccinated with FI-bRSV. In all cases, bRSV infection induced potent pulmonary CD8 T cell responses. The kinetics of the post-challenge response in L-bRSV immunized animals was accelerated compared to the FI-bRSV and PBS groups, suggesting that only the L-bRSV vaccine, and not the FI-bRSV vaccine, had primed memory T cells. The differences between primary and post-vaccination secondary infection were very minor, in terms of the proliferation status of pulmonary CD8 T cells. Functional IFN-␥ + CD8 responses were slightly higher in the FI-bRSV vaccinated animals. Furthermore, the existence of strong IFN-␥ + CD8 responses in FI-bRSV vaccinated animals after challenge suggests (i) that these IFN-␥ + responses in FI-bRSV immunized animals do not protect against immunopathology, and (ii) that Th-2 biased responses during bRSV challenge after vaccination with FI-bRSV have a limited impact on the CD8 responses in the bronchoalveolar lavage fluid. Thus, several response patterns (Th-l/Th-2) seem to co-exist during bRSV infection.

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A bovine model of vaccine enhanced respiratory syncytial virus pathophysiology

Cited by 127 publications

References 23 publications

Bovine respiratory syncytial virus infection

Bovine respiratory syncytial virus infection

Overcoming T-Cell-Mediated Immunopathology to Achieve Safe Respiratory Syncytial Virus Vaccination

Kinetics of antiviral CD8 T cell responses during primary and post-vaccination secondary bovine respiratory syncytial virus infection

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