Utility of the Neonatal Calf Model for Testing Vaccines and Intervention Strategies for Use against Human RSV Infection

Abstract

Respiratory syncytial virus (RSV) is a significant cause of pediatric respiratory tract infections. It is estimated that two-thirds of infants are infected with RSV during the first year of life and it is one of the leading causes of death in this age group worldwide. Similarly, bovine RSV is a primary viral pathogen in cases of pneumonia in young calves and plays a significant role in bovine respiratory disease complex. Importantly, naturally occurring infection of calves with bovine RSV shares many features in common with human RSV infection. Herein, we update our current understanding of RSV infection in cattle, with particular focus on similarities between the calf and human infection, and the recent reports in which the neonatal calf has been employed for the development and testing of vaccines and therapeutics which may be applied to hRSV infection in humans.

Keywords: RSV; calf model; human; therapeutics; vaccines.

Figure 1

Gross and microscopic pathology of experimental BRSV infection. (A) Lung from calf experimentally infected with bRSV and examined 7 days later. Ventral areas of right cranial and right middle lung lobes are atelectic and dark red-purple (arrows). Similar small lesions are visible in the right caudal lobe (arrowheads). The remainder of the lung failed to collapse. (B) Lung from calf experimentally infected with bRSV and examined 7 days later. There is an overall red discoloration to the lungs. Dorsal regions of all lobes are characterized by interlobular and subpleural edema (inset). (C) Photomicrograph of lung from calf experimentally infected with bRSV and examined 7 days later. There is degeneration and necrosis of bronchial epithelium with sloughed cells and debris in bronchial lumen. Some areas lack epithelium (arrows). Note epithelial syncytia (arrowheads). (D) Photomicrograph of lung from calf experimentally infected with bRSV and examined 7 days later. Interstitial capillaries are congested and alveolar interstitium contains numerous mononuclear cells. Alveolar lumina contain macrophages, neutrophils (arrowheads) and syncytia (arrow). (E) Photomicrograph of lung from calf experimentally infected with bRSV and examined 7 days later. In situ hybridization using probes for bRSV F protein (green) and IL-8 (red). (F) Photomicrograph of lung from calf experimentally infected with bRSV and examined 14 days later. Bronchiolitis obliterans; polypoid proliferative epithelium, including syncytia (arrowheads), supported by a fibrous stalk (arrows) fills bronchiolar lumen.

Figure 2

Schematic diagram of the RSV virion. Shown is the structure and organization of the RSV virion, emphasizing viral proteins targeted by the adaptive immune system.