The COVID-19 pandemic has underscored the importance of swift responses and the necessity of dependable technologies for vaccine development. Our team previously developed a fast cloning system for the modified vaccinia virus Ankara (MVA) vaccine platform. In this study, we report the construction and preclinical testing of a recombinant MVA vaccine obtained using this system. We obtained recombinant MVA expressing the unmodified full-length SARS-CoV-2 spike (S) protein containing the D614G amino acid substitution (MVA-Sdg) and a version expressing a modified S protein containing amino acid substitutions designed to stabilize the protein a in a pre-fusion conformation (MVA-Spf). S protein expressed by MVA-Sdg was found to be expressed and correctly processed and transported to the cell surface, where it efficiently produced cell-cell fusion. Version Spf, however, was not proteolytically processed and despite being transported to the plasma membrane, it failed to induce cell-cell fusion. We assessed both vaccine candidates in prime-boost regimens in the susceptible transgenic K18-human angiotensin converting enzyme 2 (K18-hACE2) mice and in golden Syrian hamsters. Robust immunity and protection from disease was induced with either vaccine in both animal models. Remarkably, the MVA-Spf vaccine candidate produced higher levels of antibodies, a stronger T cell response, and a higher degree of protection from challenge. In addition, the levels of SARS-CoV-2 in the brain of MVA-Spf inoculated mice was decreased to undetectable levels. Those results add to our current experience and range of vaccine vectors and technologies for developing a safe and effective COVID-19 vaccine

The influenza virus has been the primary cause of the pandemic, posing a constant threat to human society. Due to its genetic evolution and continuous outbreak, antiviral research currently focuses on exploring a novel lead agent. A comprehensive antiviral screening discovered a marine bacterium whose extract exerted excellent efficacy against influenza viruses. Parerythrobacter sp. M20A3S10, a novel strain under the family Erythrobacteraceae, could produce carotenoids exhibiting antiviral and anticancer activity by enhancing the cellular immune system. Post-treatment of M20A3S10 extract showed outstanding therapeutic indexes: against influenza virus A/PR8 (H1N1) [selectivity index (SI) = 24.0], A/Wisconsin/15/2009 (H3N2) (SI = 30.1) and B/Florida/78/2015 (SI = 38.2). Comparably, the effectiveness was demonstrated against Zika virus (ZIKV) and dengue virus type 2 (DENV2) with an SI of 22.5 and 24.1, respectively, namely broad-spectrum activity. Of note, the antiviral responses resulted from the common replication mechanism between IAV, ZIKV, and DENV2. The stimulation of apoptosis-mediated cellular immunity prevented the viral release and protected the host, suggesting that switching from necroptosis to apoptosis is a novel antiviral target. Although the specific compound affecting the antiviral activity was not identified, its promising efficacy with broad activity will contribute to developing a strategy for preventing future pandemics.

Epidemic diseases that arise from infectious RNA viruses, particularly influenza viruses, pose a constant threat to the global economy and public health. Viral evolution has undermined the efficacy of acquired immunity from vaccines and the antiviral effects of FDA-approved drugs. As such, there is an urgent need to develop new antiviral lead agents. Natural compounds, owing to their historical validation of application and safety, have become a promising solution. In this light, a novel marine bacterium, Pseudomonas sp. M20A4R8, has been found to exhibit significant antiviral activity [half maximal inhibitory concentration (IC50) = 1.3 µg/mL, selectivity index (SI) = 919.4] against influenza virus A/Puerto Rico/8/34, surpassing the activity of chloroquine. The antiviral response by M20A4R8 extract was induced during post-entry stages of the influenza virus, indicating suitability for post-application after the establishment of viral infection. Furthermore, post-treatment with M20A4R8 extract protected the host from virus-induced apoptosis, suggesting its potential use in acute respiratory disease complexes resulting from immune effectors' overstimulation and autophagy-mediated self-apoptosis. The extract demonstrated an outstanding therapeutic index against influenza virus A/Wisconsin/15/2009 (IC50 = 8.1 µg/mL, SI = 146.2) and B/Florida/78/2015 Victoria lineage (IC50 = 3.5 µg/mL, SI = 343.8), indicating a broad anti-influenza virus activity with guaranteed safety and effectiveness. This study provides a new perspective on mechanisms for preventing a broad spectrum of viral infections through antiviral agents from novel and natural origins. Future studies on a single or combined compound from the extract hold promise, encouraging its use in preclinical challenge tests with various influenza virus strains.