Biology subjects

Tregoning, J.

Publications and source records attributed to Tregoning, J..

3 recordsLinked to original sources

bioRxiv2026

A rhinovirus vaccine evokes T cell mediated cross-reactive immunity in a preclinical model of rhinovirus infection

Rhinovirus (RV) infection is the most common cause of acute exacerbations of respiratory diseases such as asthma and chronic obstructive pulmonary disease. Vaccines are available for two less common respiratory viruses (influenza and respiratory syncytial viruses), but development of a RV vaccine to protect patients with chronic respiratory disease has been hampered by the large number of serologically distinct RV strains ([~]180, grouped genetically into [~]80 A, [~]30 B and [~]70 C strains). We have explored the potential of the RV-A16 VP0 subunit vaccine in both CpG-adjuvanted protein subunit and mRNA formats. We demonstrate that both vaccine formats induce strong effector CD4 and CD8 T cell responses in the airways and lungs of immunized mice that rapidly expand following infection with a heterotypic RV strain and are associated with enhanced virus clearance. Adjuvanted VP0 protein subunit vaccination evoked strong germinal center reactions in the lymph nodes and markedly accelerated the production of neutralizing antibodies following heterotypic RV infection. In contrast, VP0 mRNA vaccination evoked limited germinal center responses and neutralizing antibody production. Th1 polarized immune responses were induced against a large panel of 20 heterologous RV strains representative of all RV-A, -B and -C strains. This study confirms the potential of RV VP0 vaccination as an approach to overcome the serological diversity of RV and describes the immune response evoked, including cross-strain cellular immunity and protection against heterotypic RV infection.

immunology↗

bioRxiv2025

Le click c'est chic: a plug-and-play virus-like particle vaccination platform enabled by non-canonical amino acid incorporation and click chemistry in the tobacco BY-2 cell-free protein synthesis system

Non-canonical amino acids (ncaas) can provide recombinant proteins with novel exciting functionalities beyond the limits of nature, such as orthogonal reaction groups. Notably, ncaa introduction can be used in vaccinology to enhance the adaptability and immunogenicity of putative vaccine candidates. Cell-free protein synthesis (CFPS) represents the most promising methodology to introduce ncaa into recombinant proteins of interest. However, traditionally used prokaryotic CFPS systems show limitations to produce complex proteins requiring post-translational modifications, whilst eukaryotic CFPS systems have historically been difficult to scale and show low protein yields. In this work, we establish the site-specific introduction of ncaas into complex proteins with the high-yielding and scalable eukaryotic tobacco BY-2 CFPS system (BYL), commercialised as ALiCE(R). The tyrosine transferase from Escherichia coli (eTyrT) was tested for amber suppression-mediated ncaa incorporation in BYL. eTyrT showed high incorporation yields of up to 2mg/ml recombinant protein for the azido-tyrosine and alkyne-tyrosine ncaas, with linear scalability up to 10ml without any losses in protein yield. We applied ncaa incorporation in BYL to enable click chemistry bioconjugation of the receptor binding domain (RBD) of influenza hemagglutinin to pre-assembled hepatitis B core (HBc) virus-like particles (VLPs). BYL efficiently produced the alkyne-modified RBD and azido-modified HBc VLPs, and their conjugation via copper-catalysed azide-alkyne cycloaddition (CuAAC) led to structurally intact, RBD-coated particles. VLP-RBD conjugates could efficiently hemagglutinate chicken erythrocytes where the individual proteins could not, proving both the sialic-acid binding activity of the RBD and its multivalent presentation by the HBc VLP. Finally, when used to vaccinate mice the conjugated RBD-VLPs showed a greater protection against live influenza challenge than free RBD. This research thus enables ncaa introduction for recombinant proteins produced in BYL, constructing a novel plug-and-play vaccine platform and further expanding the capabilities of BYL to produce vaccine candidates and other proteins of interest.

molecular biology↗

bioRxiv2019

Respiratory viral infection alters the gut microbiota by inducing inappetence

The gut microbiota has an important role in health and disease. Respiratory viral infections are extremely common but their impact on the composition and function of the gut microbiota is poorly understood. We previously observed a significant change in the gut microbiota after viral lung infection. Here we show that weight loss during Respiratory Syncytial Virus (RSV) or influenza virus infection was due to decreased food consumption, and that fasting mice independently of infection altered gut microbiota composition. While the acute phase TNF- response drove early weight loss and inappetence during RSV infection, this was not sufficient to induce changes in the gut microbiota. However, depleting CD8+ cells increased food intake and prevented weight loss resulting in a reversal of the gut microbiota changes normally observed during RSV infection. Viral infection also led to changes in the faecal gut metabolome during RSV infection, with a significant shift in lipid metabolism. Sphingolipids, poly-unsaturated fatty acids (PUFAs) and the short-chain fatty acid (SCFA) valerate all increased in abundance in the faecal metabolome following RSV infection. Whether this, and the impact of infection-induced anorexia on the gut microbiota, are part of a protective, anti-inflammatory response during respiratory viral infections remains to be determined.

immunology↗