An intranasal recombinant NDV-RSV F opt vaccine is safe and reduces lesion severity in a colostrum-deprived calf model of RSV infection

Authors: Sacco, Randy; MENA, IGNACIO - The Icahn School Of Medicine At Mount Sinai; Palmer, Mitchell; DURBIN, RUSSELL - New Jersey Medical School; GARCIA-SASTRE, ALDOFO - The Icahn School Of Medicine At Mount Sinai; DURBIN, JOAN - New Jersey Medical School

Submitted to: Scientific Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/21/2022
Publication Date: 12/29/2022
Citation: Sacco, R.E., Mena, I., Palmer, M.V., Durbin, R.K., Garcia-Sastre, A., Durbin, J.E. 2022. An intranasal recombinant NDV-RSV F opt vaccine is safe and reduces lesion severity in a colostrum-deprived calf model of RSV infection. Scientific Reports. 12(1). Article 22552. https://doi.org/10.1038/s41598-022-26938-w.
DOI: https://doi.org/10.1038/s41598-022-26938-w

Interpretive Summary: In this manuscript, we have developed and tested a new vaccine for a respiratory virus in calves. The disease in calves closely mimics that in humans with a related respiratory virus, so the studies conducted provide data that will also be useful in developing a new vaccine for use in humans. The vaccine developed uses a new method for delivery of a protein from the virus. The protein is encoded by vaccine virus that can be delivered into the nasal passages. Our work shows that the vaccine is safe and provided significant protection to the calves following exposure to the live virus. This work will be of interest to those studying respiratory infections and those developing new vaccines against these infections.

Technical Abstract: Human respiratory syncytial virus (HRSV) is a major cause of severe lower respiratory tract disease in infants and the elderly, yet no safe and effective vaccine is commercially available. A closely related virus, bovine RSV, causes respiratory disease in young calves, with many similar features to those seen in HRSV, gross and microscopic lesions. We previously constructed a Newcastle disease virus (NDV)-vectored vaccine that expresses the F glycoprotein of HRSVshowed that it reduced viral loads in the lungs of mice and cotton rats and protected these rodent models from HRSV challenge. However, as clinical signs and pathogenesis of the disease in these laboratory animals following HRSV infection differs from that observed in human infants, it was of interest to determine whether a similar NDV-vectored vaccine would be protective in a neonatal calf BRSV infection model. For these studies, a codon optimized rNDV- vaccine was constructed using BRSV F glycoprotein (rNDV-BRSV Fopt). The rNDV BRSV-F opt vaccine was well-tolerated by colostrum-deprived calves in which no untoward clinical signs were noted following administration of primary or booster vaccines and there was no evidence of vaccine-enhanced disease in the upper airways or lungs of calves receiving the vaccine compared to the non-vaccinated control calves. While a single intranasal administration failed to induce protection, we found that two intranasal doses reduces severity of gross and microscopic lung lesions and decreases viral load in the upper respiratory tract and lungs. In addition, neutralizing antibodies were generated in serum of colostrum-deprived calves administered the rNDV BRSV-F opt vaccine. Moreover, vaccinated calves had reduced levels of CXC chemokines in lesioned lung samples compared to non-lesioned samples. Reduced expression of these chemokines likely played a role in decreased lesion severity and a reduction in cellular infiltration into RSV-inflamed lungs. In summary, we have shown that rNDV BRSV-F opt vaccine is safe in colostrum-deprived calves, reduces severity of lung lesions, and decreases viral load in the upper respiratory tract and lungs.