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Infections with rabies virus (RABV) and related lyssaviruses are uniformly fatal once virus accesses the central nervous system (CNS) and causes disease signs. Current immunotherapies are thus focused on the early, pre‐symptomatic stage of disease, with the goal of peripheral neutralization of virus to prevent CNS infection. Here, we evaluated the therapeutic efficacy of F11, an anti‐lyssavirus human monoclonal antibody (mAb), on established lyssavirus infections. We show that a single dose of F11 limits viral load in the brain and reverses disease signs following infection with a lethal dose of lyssavirus, even when administered after initiation of robust virus replication in the CNS. Importantly, we found that F11‐dependent neutralization is not sufficient to protect animals from mortality, and a CD4 T cell‐dependent adaptive immune response is required for successful control of infection. F11 significantly changes the spectrum of leukocyte populations in the brain, and the FcRγ‐binding function of F11 contributes to therapeutic efficacy. Thus, mAb therapy can drive potent neutralization‐independent T cell‐mediated effects, even against an established CNS infection by a lethal neurotropic virus. Synopsis Rabies is a fatal viral disease of humans, with uniform mortality once central nervous system (CNS) invasion occurs and symptoms appear. This study demonstrates that a single‐dose monoclonal (mAb) therapy can yield a functional cure for rabies, even after robust CNS replication. Peripheral administration of mAb F11 reduces CNS viral replication and prevents mortality, following infection of mice with a lethal dose of either Australian bat lyssavirus (ABLV) or rabies virus (RABV). Therapeutic efficacy of F11, a human IgG1, requires a functional antibody Fc region, implicating the mechanistic involvement of immune cells bearing FcRγ. F11 efficacy requires an intact host adaptive immune response, particularly CD4 T cells. Administration of F11 alters both the proportions and phenotypes of immune cells in the brains of ABLV‐infected animals. Virus persists chronically at a low level in the brains of F11‐treated animals, but animals remain free of disease signs. Graphical Abstract Rabies is a fatal viral disease of humans, with uniform mortality once central nervous system (CNS) invasion occurs and symptoms appear. This study demonstrates that a single‐dose monoclonal (mAb) therapy can yield a functional cure for rabies, even after robust CNS replication.

Rabies is a fatal zoonosis that is considered a re-emerging infectious disease. Although rabies remains endemic in canines throughout much of the world, vaccination programs have essentially eliminated dog rabies in the Americas and much of Europe. However, despite the goal of eliminating dog rabies in the European Union by 2020, sporadic cases of dog rabies still occur in Eastern Europe, including Georgia. To assess the genetic diversity of the strains recently circulating in Georgia, we sequenced seventy-eight RABV-positive samples from the brain tissues of rabid dogs and jackals using Illumina short-read sequencing of total RNA shotgun libraries. Seventy-seven RABV genomes were successfully assembled and annotated, with seventy-four of them reaching the coding-complete status. Phylogenetic analyses of the nucleoprotein (N) and attachment glycoprotein (G) genes placed all the assembled genomes into the Cosmopolitan clade, consistent with the Georgian origin of the samples. An amino acid alignment of the G glycoprotein ectodomain identified twelve different sequences for this domain among the samples. Only one of the ectodomain groups contained a residue change in an antigenic site, an R264H change in the G5 antigenic site. Three isolates were cultured, and these were found to be efficiently neutralized by the human monoclonal antibody A6. Overall, our data show that recently circulating RABV isolates from Georgian canines are predominantly closely related phylogroup I viruses of the Cosmopolitan clade. Current human rabies vaccines should offer protection against infection by Georgian canine RABVs. The genomes have been deposited in GenBank (accessions: OQ603609-OQ603685).

Opportunities for students to conduct research in courses increase feelings of belonging in science, retention in STEM majors, and sense of ownership in a student’s educational experience. However, many research fields are challenging to bring to students: for example, deep-sea biology often requires expensive expeditions, restricting participation and accessibility. Access to deep-sea systems has been expanded by programs such as the National Oceanic and Atmospheric Administration's Ocean Exploration (NOAA Ocean Exploration), which uses telepresence to bring deep-sea exploration to a global audience. Here, we present one example of how remotely operated vehicles can engage students in original research. Students in an undergraduate Marine Biology lab at at the State University of New York at Geneseo investigated the relationship between substrate rugosity and biodiversity of cold-water coral communities and associate fauna. The study site in the Pacific Remote Islands Marine National Monument was explored by NOAA Ocean Exploration using NOAA Ship Okeanos Explorer as part of the 2017 Mountains in the Deep Expedition, EX1705. Organism density was greater at higher rugosity levels, suggesting that complex substrates support higher abundances in deep-sea communities. This research experience enhanced student’s understanding of the scientific process, appreciation for deep-sea communities, and engagement in the course. Open access deep-sea data provide impactful opportunities for students to participate in original research, increasing the accessibility and reach of deep-sea science.