Biology subjects

Corleis, B.

Publications and source records attributed to Corleis, B..

8 recordsLinked to original sources

bioRxiv2026

One and Done: A safe, adaptable single-cycle SARS-CoV-2 vaccine platform blocks XBB.1.5 infection and transmission

A next-generation SARS-CoV-2 vaccine must address the currently inadequate prevention of virus transmission, particularly against emerging variants of concern, a challenge that none of the licensed commercial vaccines fully meet. Effective control of respiratory pandemics necessitates vaccines that 1) can be rapidly adapted, 2) have high patient compliance with simple and non-invasive administration, and 3) block transmission in a virus challenge. We describe here the characterization of an updated single-cycle SARS-CoV-2 vaccine candidate (scVac), engineered as a replication-defective virus with targeted deletions of the E gene and ORF6 and ORF7a, along with a truncation of ORF3a. The candidate carries an Omicron XBB.1.5 Spike (scVacXBB), maintaining all essential antigenic properties. The vaccine demonstrated an excellent safety profile in K18-hACE2 transgenic mice, the most sensitive virulence model, with no clinical signs or adverse events observed. In the Syrian hamster model, potent systemic and mucosal immune responses were induced, along with a strong neutralizing antibody response. Notably, there was no virus transmission to co-housed naive animals, which outperforms a bivalent Omicron mRNA vaccine reference. Our results demonstrate that scVacXBB-induced immunity not only prevents disease but also effectively blocks transmission. Furthermore, the successful introduction of the XBB.1.5 Spike protein into the scVac platform demonstrates the pipelines ability to adapt quickly to any emerging variant. These findings highlight the potential of this single-cycle concept as a next-generation COVID-19 vaccine, offering robust protection with a strong safety profile.

immunology↗

bioRxiv2026

Species-specific iNOS expression distinguishes epithelial and myeloid IFNγ responses in tuberculosis

RationaleTuberculosis vaccines aim to elicit protective immunity, with IFN{gamma}-producing CD4 T cells considered central mediators of host defense. In murine models, IFN{gamma} activates macrophages to induce inducible nitric oxide synthase (iNOS), resulting in nitric oxide-dependent control of Mycobacterium tuberculosis (Mtb). ObjectiveTo define the relevance of IFN{gamma}-induced iNOS activity in humans and other natural host of virulent mycobacterial species. MethodsWe systematically compared IFN{gamma}-induced effector responses in Mtb-infected myeloid cells across species. Using bulk RNA sequencing, functional infection assays, and nitric oxide measurements, we assessed IFN{gamma} responsiveness in human and mouse macrophages. These analyses were extended to monocytes from seven mammalian species and complemented by reanalysis of publicly available single-cell RNA-sequencing datasets and spatial proteomic imaging of tuberculous granulomas. Measurements and Main ResultsSingle-cell transcriptomic reanalysis revealed minimal NOS2 expression in myeloid cells from human and non-human primate granulomas. In vitro, IFN{gamma} pretreatment failed to induce NOS2 transcription, iNOS activity, or Mtb growth restriction in human macrophages, in stark contrast to murine cells. Across species, iNOS activity was largely restricted to mice, with limited induction in cattle monocytes. Instead, human respiratory epithelial cells consistently expressed NOS2, and multiplexed ion beam imaging localized iNOS protein to epithelial compartments adjacent to granulomatous lesions. ConclusionIFN{gamma} signaling is uncoupled from iNOS induction in primate myeloid cells and epithelial compartments represent dominant sources of iNOS in human tuberculosis. These findings, challenge murine macrophage-centric paradigms and IFN{gamma}-based correlates used in TB vaccine development and central to pathophysiology of tuberculosis and other pneumonias.

immunology↗

bioRxiv2025

Spontaneous preputial gland adenitis in Staphylococcus aureus-colonized male C57Bl/6 mice triggers a Th17-driven immune response

Colonization with the pathobiont Staphylococcus aureus increases the risk of endogenous S. aureus infections if the balance between host and microbe is disturbed. We developed a model of persistent S. aureus colonization using the mouse-adapted strain JSNZ. The bacteria transfer from parents to offspring, producing lifelong, usually asymptomatic colonization. Here we report that S. aureus-colonized adult male mice frequently develop spontaneous preputial gland infections (preputial gland adenitis, PGA), which are characterized by pronounced pus production and gland enlargement. This study aimed to characterize PGA in terms of phenotype, causative agents, and the pathogen-specific antibody and T cell responses. We compared three groups: naive mice, colonized PGA-negative mice, and colonized PGA-positive mice. PGA occurred in 8/12 (67%) of male breeding animals and in 17/25 (68%) of adult male offspring. The infection did not self-resolve and persisted for several months. Genotyping identified the colonizing strain JSNZ as the causative agent. The infection caused purulent inflammation, with massive bacterial aggregates and neutrophil infiltrates filling the gland lumen. This inflammation completely disrupted the glandular architecture. PGA induced a strong but localized release of IL-1, IL-1{beta}, IL-17, MIP-1, and KC in the infected gland. T cells from PGA-draining lymph nodes, as well as splenocytes, reacted to in vitro re-stimulation with a S. aureus antigen cocktail with the proliferation of Th17 cells, and the release of IL-17 and IFN-{gamma}, corresponding to a type 3/1- immune response. Colonized PGA-positive mice also mounted a robust S. aureus-specific serum antibody response. In conclusion, the pathology of this spontaneous, chronic S. aureus infection is driven by a strong, type 3-biased immune response that, however, fails to clear the bacteria. This endogenous PGA model provides a valuable tool for studying host-pathogen interactions in natural S. aureus infection.

microbiology↗

bioRxiv2024

Outcome of H5N1 clade 2.3.4.4b virus infection in calves and lactating cows

In March 2024, highly pathogenic avian influenza virus (HPAIV) clade 2.3.4.4b H5N1 infections in dairy cows were first reported from Texas, USA. Rapid dissemination to more than 190 farms in 13 states followed. Here, we provide results of two independent clade 2.3.4.4b experimental infection studies evaluating (i) oronasal susceptibility and transmission in calves to a US H5N1 bovine isolate genotype B3.13 (H5N1 B3.13) and (ii) susceptibility of lactating cows following direct mammary gland inoculation of either H5N1 B3.13 or a current EU H5N1 wild bird isolate genotype euDG (H5N1 euDG). Inoculation of the calves resulted in moderate nasal replication and shedding with no severe clinical signs or transmission to sentinel calves. In dairy cows, infection resulted in no nasal shedding, but severe acute mammary gland infection with necrotizing mastitis and high fever was observed for both H5N1 genotypes/strains. Milk production was rapidly and drastically reduced and the physical condition of the cows was severely compromised. Virus titers in milk rapidly peaked at 108 TCID50/mL, but systemic infection did not ensue. Notably, adaptive mutation PB2 E627K emerged after intramammary replication of H5N1 euDG. Our data suggest that in addition to H5N1 B3.13, other HPAIV H5N1 strains have the potential to replicate in the udder of cows and that milk and milking procedures, rather than respiratory spread, are likely the primary routes of H5N1 transmission between cattle.

microbiology↗

bioRxiv2023

Assessment of Immunogenicity and Efficacy of CV0501 mRNA-based Omicron COVID-19 Vaccination in Small Animal Models

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron and its subvariants (BA.2, BA.4, BA.5) represent the most commonly circulating variants of concern (VOC) in the coronavirus disease 2019 (COVID-19) pandemic in 2022. Despite high vaccination rates with approved SARS-CoV-2 vaccines encoding the ancestral spike (S) protein, these Omicron subvariants have collectively resulted in increased viral transmission and disease incidence. This necessitates the development and characterization of vaccines incorporating later emerging S proteins to enhance protection against VOC. In this context, bivalent vaccine formulations may induce broad protection against VOC and potential future SARS-CoV-2 variants. Here, we report preclinical data for a lipid nanoparticle (LNP)-formulated RNActive(R) N1-methylpseudouridine (N1m{Psi}) modified mRNA vaccine (CV0501) based on our second-generation SARS-CoV-2 vaccine CV2CoV, encoding the S protein of Omicron BA.1. The immunogenicity of CV0501, alone or in combination with a corresponding vaccine encoding the ancestral S protein (ancestral N1m{Psi}), was first measured in dose-response and booster immunization studies performed in Wistar rats. Both monovalent CV0501 and bivalent CV0501/ancestral N1m{Psi} immunization induced robust neutralizing antibody titers against the BA.1, BA.2 and BA.5 Omicron subvariants, in addition to other SARS-CoV-2 variants in a booster immunization study. The protective efficacy of monovalent CV0501 against live SARS-CoV-2 BA.2 infection was then assessed in hamsters. Monovalent CV0501 significantly reduced SARS-CoV-2 BA.2 viral loads in the airways, demonstrating protection induced by CV0501 vaccination. CV0501 has now advanced into human Phase 1 clinical trials (ClinicalTrials.gov Identifier: NCT05477186).

immunology↗

bioRxiv2022

Tobacco smoke exposure results in recruitment of inflammatory airspace monocytes and accelerated growth of Mycobacterium tuberculosis

Tobacco smoking doubles the risk of active tuberculosis (TB) and accounts for up to 20% of all active TB cases globally. How smoking promotes lung microenvironments permissive to Mycobacterium tuberculosis (Mtb) growth remains incompletely understood. We investigated primary bronchoalveolar lavage cells from current- and never-smokers by performing single-cell RNA-sequencing (scRNA-seq), flow cytometry, and functional assays. We observed enrichment of immature inflammatory monocytes in the lungs of smokers compared to non-smokers. These monocytes exhibited phenotypes consistent with recent recruitment from blood, ongoing differentiation, increased activation, and states similar to those with chronic obstructive pulmonary disease (COPD). Using integrative scRNA-seq and flow cytometry, we identify CD93 as a marker for a subset of these newly recruited smoking-associated lung monocytes and further provide evidence that recruitment of monocytes into the lung is mediated by CCL11 binding to CCR2. We also show that these cells exhibit elevated inflammatory responses upon exposure to Mtb and accelerated intracellular growth of Mtb compared to mature macrophages. This elevated Mtb growth could be inhibited with an anti-inflammatory small molecule, providing a direct connection between smoking-induced pro-inflammatory states and permissiveness to Mtb growth. Our findings suggest a model in which smoking leads to recruitment of immature inflammatory monocytes from the periphery to the lung via CCL11-CCR2 interactions, which results in the accumulation of these Mtb permissive cells in the airway. This work defines how smoking may lead to increased susceptibility to Mtb and identifies novel host-directed therapies to reduce the burden of TB among those who smoke. One Sentence SummaryInflammatory monocytes are recruited to the airways of smokers where they may contribute to more rapid growth of Mycobacterium tuberculosis in the lungs.

immunology↗

bioRxiv2022

Low-dose bivalent mRNA vaccine is highly effective against different SARS-CoV-2 variants in a transgenic mouse model

Combining optimized spike (S) protein-encoding mRNA vaccines to target multiple SARS-CoV-2 variants could improve COVID-19 control. We compared monovalent and bivalent mRNA vaccines encoding B.1.351 (Beta) and/or B.1.617.2 (Delta) SARS-CoV-2 S-protein, primarily in a transgenic mouse model and a Wistar rat model. The low-dose bivalent mRNA vaccine contained half the mRNA of each respective monovalent vaccine, but induced comparable neutralizing antibody titres, enrichment of lung-resident memory CD8+ T cells, specific CD4+ and CD8+ responses, and fully protected transgenic mice from SARS-CoV-2 lethality. The bivalent mRNA vaccine significantly reduced viral replication in both Beta- and Delta-challenged mice. Sera from bivalent mRNA vaccine immunized Wistar rats also contained neutralizing antibodies against the B.1.1.529 (Omicron BA.1) variant. These data suggest that low-dose and fit-for-purpose multivalent mRNA vaccines encoding distinct S-proteins is a feasible approach for increasing the potency of vaccines against emerging and co-circulating SARS-CoV-2 variants.

immunology↗

bioRxiv2021

CVnCoV protects human ACE2 transgenic mice from ancestral B BavPat1 and emerging B.1.351 SARS-CoV-2

The ongoing severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic necessitates the fast development of vaccines as the primary control option. Recently, viral mutants termed "variants of concern" (VOC) have emerged with the potential to escape host immunity. VOC B.1.351 was first discovered in South Africa in late 2020, and causes global concern due to poor neutralization with propensity to evade preexisting immunity from ancestral strains. We tested the efficacy of a spike encoding mRNA vaccine (CVnCoV) against the ancestral strain BavPat1 and the novel VOC B.1.351 in a K18-hACE2 transgenic mouse model. Naive mice and mice immunized with formalin-inactivated SARS-CoV-2 preparation were used as controls. mRNA-immunized mice developed elevated SARS-CoV-2 RBD-specific antibody as well as neutralization titers against the ancestral strain BavPat1. Neutralization titers against VOC B.1.351 were readily detectable but significantly reduced compared to BavPat1. VOC B.1.351-infected control animals experienced a delayed course of disease, yet nearly all SARS-CoV-2 challenged naive mice succumbed with virus dissemination and high viral loads. CVnCoV vaccine completely protected the animals from disease and mortality caused by either viral strain. Moreover, SARS-CoV-2 was not detected in oral swabs, lung, or brain in these groups. Only partial protection was observed in mice receiving the formalin-inactivated virus preparation. Despite lower neutralizing antibody titers compared to the ancestral strain BavPat1, CVnCoV shows complete disease protection against the novel VOC B.1.351 in our studies.

microbiology↗