Intranasal or airborne transmission-mediated delivery of an attenuated SARS-CoV-2 protects Syrian hamsters against new variants

Charles B. Stauft, Prabhuanand Selvaraj, Felice D’Agnillo, Clement A. Meseda, Shufeng Liu, Cyntia L. Pedro, Kotou Sangare, Christopher Z. Lien, Jerry P. Weir, Matthew F. Starost and Tony T. Wang ()
Additional contact information
Charles B. Stauft: Food and Drug Administration
Prabhuanand Selvaraj: Food and Drug Administration
Felice D’Agnillo: Food and Drug Administration
Clement A. Meseda: Food and Drug Administration
Shufeng Liu: Food and Drug Administration
Cyntia L. Pedro: Food and Drug Administration
Kotou Sangare: Food and Drug Administration
Christopher Z. Lien: Food and Drug Administration
Jerry P. Weir: Food and Drug Administration
Matthew F. Starost: National Institutes of Health
Tony T. Wang: Food and Drug Administration

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract Detection of secretory antibodies in the airway is highly desirable when evaluating mucosal protection by vaccines against a respiratory virus, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We show that intranasal delivery of an attenuated SARS-CoV-2 (Nsp1-K164A/H165A) induces both mucosal and systemic IgA and IgG in male Syrian hamsters. Interestingly, either direct intranasal immunization or airborne transmission-mediated delivery of Nsp1-K164A/H165A in Syrian hamsters offers protection against heterologous challenge with variants of concern (VOCs) including Delta, Omicron BA.1, BA.2.12.1 and BA.5. Vaccinated animals show significant reduction in both tissue viral loads and lung inflammation. Similarly attenuated viruses bearing BA.1 and BA.5 spike boost variant-specific neutralizing antibodies in male mice that were first vaccinated with modified vaccinia virus Ankara vectors (MVA) expressing full-length WA1/2020 Spike protein. Together, these results demonstrate that our attenuated virus may be a promising nasal vaccine candidate for boosting mucosal immunity against future SARS-CoV-2 VOCs.

Date: 2023
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DOI: 10.1038/s41467-023-39090-4

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