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.
Using multiple cell types and isolates of Delta and Omicron variants of SARS-CoV-2, we report differences in virus production, replication, and infectivity in vitro. Ancestral and Delta SARS-CoV-2 variant exhibit reduced virus production and replication at 34°C compared to 37°C while Omicron replication is balanced between temperatures.
Despite being more transmissible, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant was found to cause milder diseases in laboratory animals, often accompanied by a lower viral load compared to previous variants of concern. This study revealed the structural basis for a robust interaction between the receptor binding domain of the Omicron spike protein and mouse ACE2. Pseudovirus bearing the Omicron spike protein efficiently utilized mouse ACE2 for entry. By comparing viral load and disease severity among laboratory mice infected by a natural Omicron variant or ancestral viruses bearing either the entire Omicron Spike or only the N501Y/Q493R mutations in its spike, we found that mutations outside the spike protein in the Omicron variant may be responsible for the observed lower viral load. Together, our results indicated that a post-entry block to the Omicron variant exists in laboratory mice.
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