Biology subjects

Courant, T.

Publications and source records attributed to Courant, T..

3 recordsLinked to original sources

bioRxiv2024

A Single Chimeric Spike Antigen Induces Pan-Sarbecovirus Immunity

Next-generation vaccines are required to address the evolving nature of SARS-CoV-2 and to protect against emerging pandemic threats from other coronaviruses. These vaccines should aim to elicit broad-protection, provide long-lasting immunity and facilitate equitable access for all populations. In this study, a panel of chimeric, full-length spike antigens were developed that incorporate mutations from previous, circulating and predicted SARS-CoV-2 variants. The lead candidate (CoVEXS5) was obtained from a high-yield production process in stable CHO cells with purity of >95%, long-term stability and elicitation of broadly cross-reactive neutralising antibodies when delivered to mice in a squalene emulsion adjuvant (Sepivac SWE). In both mice and hamsters, CoVEXS5 immunisation reduced clinical disease signs, lung inflammation and organ viral titres after SARS-CoV-2 infection, including challenge with the highly immunoevasive Omicron XBB.1.5 subvariant. In mice previously primed with a licenced protein vaccine (NVX-CoV2373), CoVEXS5 could boost T cell immunity, as well as neutralising antibodies levels against viruses from three sarbecoviruses clades. The breadth of sarbecovirus cross-reactivity elicited by CoVEXS5 exceeded that observed after boosting with the NVX-CoV2373 vaccine. These findings highlight the potential of a chimeric spike antigen, formulated in an open-access adjuvant, as a next-generation vaccine candidate to enhance cross-protection against emerging sarbecoviruses in vaccinated populations globally.

immunology↗

bioRxiv2024

Ex vivo Model of Functioning Human Lymph Node Reveals Pivotal Role for Innate Lymphoid Cells and Stromal Populations in Response to Vaccine Adjuvant

Immunological processes that underpin the administration of therapeutics and vaccines are poorly defined due to a lack of models which faithfully recapitulate human immune responses. Inbred mice lack the diversity inherent to people, while the microanatomical organisation of human tissue is lost in isolated cell suspensions. We describe precision-cut human lymph node (LN) slices as architecturally-preserved, functioning lymphoid tissue model system, and explore early inflammatory responses to a potent vaccine liposomal adjuvant containing a TLR4-agonist and QS21 saponin. Combining scRNA-seq, multiplexed immunofluorescence and secretome analysis, we dissect direct and indirect signalling pathways in both leukocytes and stromal cells to reveal communication networks linking innate and adaptive immunity. Application of molecular inhibitors reveals that secretion of IL-1{beta}, but not IL-18, is TLR4-dependent in human LN. Retaining donor-to-donor immune variation, this ex vivo LN model system enables the study of pathways previously difficult to observe in humans, paving the way towards precision medicine.

immunology↗

bioRxiv2021

Engineered SARS-CoV-2 receptor binding domain improves immunogenicity in mice and elicits protective immunity in hamsters

Global containment of COVID-19 still requires accessible and affordable vaccines for low- and middle-income countries (LMICs).1 Recently approved vaccines provide needed interventions, albeit at prices that may limit their global access.2 Subunit vaccines based on recombinant proteins are suited for large-volume microbial manufacturing to yield billions of doses annually, minimizing their manufacturing costs.3 These types of vaccines are well-established, proven interventions with multiple safe and efficacious commercial examples.4-6 Many vaccine candidates of this type for SARS-CoV-2 rely on sequences containing the receptor-binding domain (RBD), which mediates viral entry to cells via ACE2.7,8 Here we report an engineered sequence variant of RBD that exhibits high-yield manufacturability, high-affinity binding to ACE2, and enhanced immunogenicity after a single dose in mice compared to the Wuhan-Hu-1 variant used in current vaccines. Antibodies raised against the engineered protein exhibited heterotypic binding to the RBD from two recently reported SARS-CoV-2 variants of concern (501Y.V1/V2). Presentation of the engineered RBD on a designed virus-like particle (VLP) also reduced weight loss in hamsters upon viral challenge.

molecular biology↗