ABSTRACT
In this study, we showed that a codon optimized version of the spike (S) protein of SARS-CoV-2 can migrate to the cell membrane. However, efficient production of Moloney murine leukemia (MLV) infectious viral particles was only achieved with stable expression of a shorter S version in C-terminal (ΔS) in MLV Gag-pol expressing cells. As compared to transient transfections, this platform generated viruses with a 1000-fold higher titer. ΔS was 15-times more efficiently incorporated into VLPs as compared to S, and that was not due to steric interference between the cytoplasmic tail and the MLV capsid, as similar differences were also observed with extracellular vesicles. The amount of ΔS incorporated into VLPs released from producer cells was high and estimated at 1.25 µg/mL S2 equivalent (S is comprised of S1 and S2). The resulting VLPs could potentially be used alone or as a boost of other immunization strategies for COVID-19.
Subject(s)
COVID-19 Vaccines/immunology , Spike Glycoprotein, Coronavirus/biosynthesis , Virion/genetics , Cell Line , Humans , Moloney murine leukemia virus/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Vaccines, Synthetic/immunology , Virion/immunologyABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which rapidly became a pandemic of global proportions. Sepsis is commonly present with high lethality in the severe forms of the disease. The virus-induced cytokine storm puts the immune system in overdrive at the expense of the pathogen-specific immune response and is likely to underlie the most advanced COVID-19 clinical features, including sepsis-related multiple organ dysfunction as well as the pathophysiological changes found in the lungs. We review the major therapeutic strategies that have been considered for sepsis and might be amenable to repurposing for COVID-19. We also discuss two different immunization strategies that have the potential to confer antiviral heterologous protection: innate-induced trained immunity and adaptive-induced immune response resetting.