A trivalent mucosal vaccine encoding phylogenetically inferred ancestral RBD sequences confers pan-Sarbecovirus protection in mice.

The continued emergence of SARS-CoV-2 variants and the threat of future Sarbecovirus zoonoses have spurred the design of vaccines that can induce broad immunity against multiple coronaviruses. Here, we use computational methods to infer ancestral phylogenetic reconstructions of receptor binding domain (RBD) sequences across multiple Sarbecovirus clades and incorporate them into a multivalent adenoviral-vectored vaccine. Mice immunized with this pan-Sarbecovirus vaccine are protected in the upper and lower respiratory tracts against infection by historical and contemporary SARS-CoV-2 variants, SARS-CoV, and pre-emergent SHC014 and Pangolin/GD coronavirus strains.

The molecular toll pathway repertoire in anopheline mosquitoes.

Innate immunity in mosquitoes has received much attention due to its potential impact on vector competence for vector-borne disease pathogens, including malaria parasites. The nuclear factor (NF)-κB-dependent Toll pathway is a major regulator of innate immunity in insects. In mosquitoes, this pathway controls transcription of the majority of the known canonical humoral immune effectors, mediates anti-bacterial, anti-fungal and anti-viral immune responses, and contributes to malaria parasite killing.

The Molecular Toll Pathway Repertoire in Anopheline Mosquitoes.

Innate immunity in mosquitoes has received much attention due to its potential impact on vector competence for vector-borne disease pathogens, including malaria parasites. The nuclear factor (NF)-κB-dependent Toll pathway is a major regulator of innate immunity in insects. In mosquitoes, this pathway controls transcription of the majority of the known canonical humoral immune effectors, mediates anti-bacterial, anti-fungal and anti-viral immune responses, and contributes to malaria parasite killing.

Establishment of a Reference Material in Quality Control for Use in Infectivity and Identity Assays of Recombinant COVID-19 Vaccine, in Accordance with International Standards Organization Guidance.

The COVID-19 pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), began in 2019. One of the strategies for pandemic control was mass vaccination. In Brazil, the recombinant COVID-19 vaccine (RCV) was produced on a large scale and offered at no charge to the population.

Oral pharmacokinetics and efficacy of oral phospholipid remdesivir nucleoside prodrugs against SARS-CoV-2 in mice.

Oral broad-spectrum antivirals are urgently needed for the treatment of many emerging and contemporary RNA viruses. We previously synthesized 1--octadecyl-2--benzyl--glyceryl-P-RVn (ODBG-P-RVn, V2043), a phospholipid prodrug of GS-441524 (remdesivir nucleoside, RVn), and demonstrated its efficacy in a SARS-CoV-2 mouse model. Structure-activity relationship studies focusing on the prodrug scaffold identified two modifications, 3-fluoro-4-methoxy-benzyl (V2053) and 4-cyano-benzyl (V2067), that significantly enhanced the broad-spectrum antiviral activity against multiple RNA viruses when compared to V2043.