Replication-Competent Vesicular Stomatitis Virus Vaccine Vector Protects against SARS-CoV-2-Mediated Pathogenesis in Mice.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of human infections, and an effective vaccine is critical to mitigate coronavirus-induced disease 2019 (COVID-19). Previously, we developed a replication-competent vesicular stomatitis virus (VSV) expressing a modified form of the SARS-CoV-2 spike gene in place of the native glycoprotein gene (VSV-eGFP-SARS-CoV-2). Here, we show that vaccination with VSV-eGFP-SARS-CoV-2 generates neutralizing immune responses and protects mice from SARS-CoV-2. Immunization of mice with VSV-eGFP-SARS-CoV-2 elicits high antibody titers that neutralize SARS-CoV-2 and target the receptor binding domain that engages human angiotensin-converting enzyme-2 (ACE2). Upon challenge with a human isolate of SARS-CoV-2, mice that expressed human ACE2 and were immunized with VSV-eGFP-SARS-CoV-2 show profoundly reduced viral infection and inflammation in the lung, indicating protection against pneumonia. Passive transfer of sera from VSV-eGFP-SARS-CoV-2-immunized animals also protects naive mice from SARS-CoV-2 challenge. These data support development of VSV-SARS-CoV-2 as an attenuated, replication-competent vaccine against SARS-CoV-2.

Case JB ，Rothlauf PW ，Chen RE ，Kafai NM ，Fox JM ，Smith BK ，Shrihari S ，McCune BT ，Harvey IB ，Keeler SP ，Bloyet LM ，Zhao H ，Ma M ，Adams LJ ，Winkler ES ，Holtzman MJ ，Fremont DH ，Whelan SPJ ，Diamond MS ... -  《-》

Neutralizing Antibody and Soluble ACE2 Inhibition of a Replication-Competent VSV-SARS-CoV-2 and a Clinical Isolate of SARS-CoV-2.

Antibody-based interventions against SARS-CoV-2 could limit morbidity, mortality, and possibly transmission. An anticipated correlate of such countermeasures is the level of neutralizing antibodies against the SARS-CoV-2 spike protein, which engages with host ACE2 receptor for entry. Using an infectious molecular clone of vesicular stomatitis virus (VSV) expressing eGFP as a marker of infection, we replaced the glycoprotein gene (G) with the spike protein of SARS-CoV-2 (VSV-eGFP-SARS-CoV-2) and developed a high-throughput-imaging-based neutralization assay at biosafety level 2. We also developed a focus-reduction neutralization test with a clinical isolate of SARS-CoV-2 at biosafety level 3. Comparing the neutralizing activities of various antibodies and ACE2-Fc soluble decoy protein in both assays revealed a high degree of concordance. These assays will help define correlates of protection for antibody-based countermeasures and vaccines against SARS-CoV-2. Additionally, replication-competent VSV-eGFP-SARS-CoV-2 provides a tool for testing inhibitors of SARS-CoV-2 mediated entry under reduced biosafety containment.

Case JB ，Rothlauf PW ，Chen RE ，Liu Z ，Zhao H ，Kim AS ，Bloyet LM ，Zeng Q ，Tahan S ，Droit L ，Ilagan MXG ，Tartell MA ，Amarasinghe G ，Henderson JP ，Miersch S ，Ustav M ，Sidhu S ，Virgin HW ，Wang D ，Ding S ，Corti D ，Theel ES ，Fremont DH ，Diamond MS ，Whelan SPJ ... -  《-》

A Replication-Competent Vesicular Stomatitis Virus for Studies of SARS-CoV-2 Spike-Mediated Cell Entry and Its Inhibition.

There is an urgent need for vaccines and therapeutics to prevent and treat COVID-19. Rapid SARS-CoV-2 countermeasure development is contingent on the availability of robust, scalable, and readily deployable surrogate viral assays to screen antiviral humoral responses, define correlates of immune protection, and down-select candidate antivirals. Here, we generate a highly infectious recombinant vesicular stomatitis virus (VSV) bearing the SARS-CoV-2 spike glycoprotein S as its sole entry glycoprotein and show that this recombinant virus, rVSV-SARS-CoV-2 S, closely resembles SARS-CoV-2 in its entry-related properties. The neutralizing activities of a large panel of COVID-19 convalescent sera can be assessed in a high-throughput fluorescent reporter assay with rVSV-SARS-CoV-2 S, and neutralization of rVSV-SARS-CoV-2 S and authentic SARS-CoV-2 by spike-specific antibodies in these antisera is highly correlated. Our findings underscore the utility of rVSV-SARS-CoV-2 S for the development of spike-specific therapeutics and for mechanistic studies of viral entry and its inhibition.

Dieterle ME ，Haslwanter D ，Bortz RH 3rd ，Wirchnianski AS ，Lasso G ，Vergnolle O ，Abbasi SA ，Fels JM ，Laudermilch E ，Florez C ，Mengotto A ，Kimmel D ，Malonis RJ ，Georgiev G ，Quiroz J ，Barnhill J ，Pirofski LA ，Daily JP ，Dye JM ，Lai JR ，Herbert AS ，Chandran K ，Jangra RK ... -  《-》

Replication-competent vesicular stomatitis virus vaccine vector protects against SARS-CoV-2-mediated pathogenesis.

Case JB ，Rothlauf PW ，Chen RE ，Kafai NM ，Fox JM ，Shrihari S ，McCune BT ，Harvey IB ，Smith B ，Keeler SP ，Bloyet LM ，Winkler ES ，Holtzman MJ ，Fremont DH ，Whelan SPJ ，Diamond MS ... -  《-》

A Methyltransferase-Defective Vesicular Stomatitis Virus-Based SARS-CoV-2 Vaccine Candidate Provides Complete Protection against SARS-CoV-2 Infection in Hamsters.

Lu M ，Zhang Y ，Dravid P ，Li A ，Zeng C ，Kc M ，Trivedi S ，Sharma H ，Chaiwatpongsakorn S ，Zani A ，Kenney A ，Cai C ，Ye C ，Liang X ，Qiu J ，Martinez-Sobrido L ，Yount JS ，Boyaka PN ，Liu SL ，Peeples ME ，Kapoor A ，Li J ... -  《-》