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

Sacco, Randy E.; Mena, Ignacio; Palmer, Mitchell V.; Durbin, Russell K.; García-Sastre, Adolfo; Durbin, Joan E.

doi:10.1038/s41598-022-26938-w

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

Journal Article · Thu Dec 29 00:00:00 EST 2022 · Scientific Reports

DOI:https://doi.org/10.1038/s41598-022-26938-w· OSTI ID:2425583

Sacco, Randy E. ^[1]; Mena, Ignacio ^[2]; Palmer, Mitchell V. ^[3]; Durbin, Russell K. ^[4]; García-Sastre, Adolfo ^[2]; Durbin, Joan E. ^[4]

National Animal Disease Center/USDA/ARS, Ames, IA (United States)
Icahn School of Medicine at Mount Sinai, New York, NY (United States)
USDA/ARS, Ames, IA (United States)
Rutgers-New Jersey Medical School, Newark, NJ (United States)

Human respiratory syncytial virus (HRSV) is a major cause of severe lower respiratory tract disease in infants and the elderly, yet no safe, effective vaccine is commercially available. Closely related bovine RSV (BRSV) causes respiratory disease in young calves, with many similar features to those seen in HRSV. We previously showed that a Newcastle disease virus (NDV)-vectored vaccine expressing the F glycoprotein of HRSV reduced viral loads in lungs of mice and cotton rats and protected from HRSV. However, clinical signs and pathogenesis of disease in laboratory animals following HRSV infection differs from that observed in human infants. Thus, we examined whether a similar vaccine would protect neonatal calves from BRSV infection. Codon-optimized rNDV vaccine (rNDV-BRSV F_opt) was constructed and administered to colostrum-deprived calves. The rNDV-BRSV F_opt vaccine was well-tolerated and there was no evidence of vaccine-enhanced disease in the upper airways or lungs of these calves compared to the non-vaccinated calves. We found two intranasal doses reduces severity of gross and microscopic lesions and decreases viral load in the lungs. Furthermore, serum neutralizing antibodies were generated in vaccinated calves. Finally, reduced lung CXC chemokine levels were observed in vaccinated calves after BRSV challenge. In summary, we have shown that rNDV-BRSV F_opt vaccine is safe in colostrum-deprived calves, and is effective in reducing lung lesions, and decreasing viral load in upper respiratory tract and lungs after challenge.

View Accepted Manuscript (DOE)

Research Organization:: Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: SC0014664

OSTI ID:: 2425583

Journal Information:: Scientific Reports, Journal Name: Scientific Reports Journal Issue: 1 Vol. 12; ISSN 2045-2322

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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

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