Prator, C. A. | bioRxiv Science

bioRxiv2025

Single-dose VSV-Sudan virus vaccine protects from lethal Sudan virus infection within one week: a challenge study in macaques

BackgroundThe Sudan virus (SUDV) outbreaks in recent years including the ongoing outbreak in Uganda created a public health emergency beyond the Eastern Africa region. Currently, there are licensed countermeasures for Ebola virus (EBOV); however, there are no licensed vaccines or therapeutics against SUDV. MethodsWe developed a vesicular stomatitis virus (VSV)-based vaccine expressing the SUDV glycoprotein. Cynomolgus macaques were vaccinated intramuscularly with a single dose of VSV-SUDV either one month or one week prior to SUDV challenge. A third group was vaccinated with a single dose of VSV-EBOV one month prior to SUDV challenge to assess its cross-protective potential, and a control group received an unrelated VSV-based vaccine. ResultsAll vaccinated nonhuman primates (NHPs) developed antigen-specific IgG within 2 weeks of vaccination, including cross-reactive responses. After challenge with a lethal dose of SUDV, all VSV-SUDV-vaccinated NHPs were uniformly protected from disease. In contrast, the VSV-EBOV-vaccinated and control NHPs succumbed to disease between day 5 and 7 after challenge presenting with classical signs of Sudan virus disease associated with high titer viremia, high viral organ load, dysregulated cytokine profiles and typical pathological changes. The humoral immune response in the NHPs vaccinated with VSV-SUDV one month before challenge resulted in a profound and sustained antibody response with a diverse functionality profile which was not observed to the same extend in NHPs vaccinated one week before challenge. InterpretationWe demonstrated that a single dose of VSV-SUDV protected NHPs from lethal SUDV infection within one week. The fast-acting nature makes VSV-SUDV an ideal countermeasure for ring vaccination during outbreaks of Sudan virus disease. In contrast, VSV-EBOV provided no relevant protection against SUDV infection in NHPs highlighting the need for species-specific filovirus vaccines.

microbiology↗

bioRxiv2022

Metabolic strategies shared by basement residents of the Lost City hydrothermal field

Alkaline fluids venting from chimneys of the Lost City hydrothermal field flow from a potentially vast microbial habitat within the seafloor where energy and organic molecules are released by chemical reactions within rocks uplifted from Earths mantle. In this study, we investigated hydrothermal fluids venting from Lost City chimneys as windows into subseafloor environments where the products of geochemical reactions, such as hydrogen (H2), formate, and methane, may be the only available sources of energy for biological activity. Our deep sequencing of metagenomes and metatranscriptomes from these hydrothermal fluids revealed a few key species of archaea and bacteria that are likely to play critical roles in the subseafloor microbial ecosystem. We identified a population of Thermodesulfovibrionales (belonging to phylum Nitrospirae) as a prevalent sulfate-reducing bacterium that may be responsible for much of the consumption of H2 and sulfate in Lost City fluids. Metagenome-assembled genomes (MAGs) classified as Methanosarcinaceae and Candidatus Bipolaricaulota were also recovered from venting fluids and represent potential methanogenic and acetogenic members of the subseafloor ecosystem. These genomes share novel hydrogenases and formate dehydrogenase-like sequences that may be unique to hydrothermal and subsurface alkaline environments where hydrogen and formate are much more abundant than carbon dioxide. The results of this study include multiple examples of metabolic strategies that appear to be advantageous in hydrothermal and subsurface environments where energy and carbon are provided by geochemical reactions. IMPORTANCEThe Lost City hydrothermal field is an iconic example of a microbial ecosystem fueled by energy and carbon from Earths mantle. Uplift of mantle rocks into the seafloor can trigger a process known as serpentinization that releases hydrogen and creates unusual environmental conditions where simple organic carbon molecules are more stable than dissolved inorganic carbon. This study provides an initial glimpse into the kinds of microbes that live deep within the seafloor where serpentinization takes place, by sampling hydrothermal fluids exiting from the Lost City chimneys. The metabolic strategies that these microbes appear to be using are also shared by microbes that inhabit other sites of serpentinization, including continental subsurface environments and natural springs. Therefore, the results of this study contribute to a broader, interdisciplinary effort to understand the general principles and mechanisms by which serpentinization-associated processes can support life on Earth and perhaps other worlds.

microbiology↗