Repurposing the oncolytic virus VSV∆51M as a COVID-19 vaccine.

The coronavirus disease 2019 (COVID-19) pandemic imposes an urgent and continued need for the development of safe and cost-effective vaccines to induce preventive responses for limiting major outbreaks around the world. To combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we repurposed the VSV∆51M oncolytic virus platform to express the spike receptor-binding domain (RBD) antigen. In this study, we report the development and characterization of the VSV∆51M-RBD vaccine. Our findings demonstrate successful expression of the RBD gene by the VSV∆51M-RBD virus, inducing anti-RBD responses without attenuating the virus. Moreover, the VSV∆51M-RBD vaccine exhibited safety, immunogenicity, and the potential to serve as a safe and effective alternative or complementary platform to current COVID-19 vaccines.

Gut inflammation and adaptive immunity amplify acetaminophen toxicity in bowel and liver.

BACKGROUND AND AIM: Prevention of liver failure arising from accidental or deliberate paracetamol (acetaminophen [APAP]) overdose remains a vexed health problem despite well-publicized guidelines for its early detection and treatment. It is recognized that the gut may aggravate liver pathology, via the gut-liver axis. The main aim of this study was to assess the role of the colon in APAP-induced liver toxicity. METHODS: Liver necrosis and colitis were studied following sublethal doses of APAP administered intraperitoneally to C57Bl/6 wild-type (WT) mice, as well as to C57Bl/6 Winnie mice, which develop a spontaneous colitis caused by a SNP in Muc2, and WT mice with acute DSS-induced colitis. Repeated APAP exposure was studied in WT and Rag1 ko mice that lack mature T and B lymphocytes. RESULTS: APAP overdose resulted in significant colonic injury in WT mice (P < 0.05), which resolved by 24 h. Underlying colitis was not associated with liver necrosis, but colitis exacerbated APAP-induced liver injury and extended APAP-colonic injury. Prior APAP exposure exacerbated both APAP-liver and APAP-colonic injury more so in WT than Rag1 ko mice. APAP impaired barrier function with increased intestinal permeability and associated bacterial translocation to the liver and spleen in mice with the Winnie phenotype. CONCLUSIONS: This study identifies novel roles for APAP in causing colitis, the amplification of APAP-liver toxicity where there is underlying colitis, and involvement of immune memory in APAP-toxicity. The latter could be key for decoding the poorly understood but important clinical entity of chronic APAP liver failure.

The role of IL-22 in the resolution of sterile and nonsterile inflammation.

In a broad sense, inflammation can be conveniently characterised by two phases: the first phase, which is a pro-inflammatory, has evolved to clear infection and/or injured tissue; and the second phase concerns regeneration of normal tissue and restitution of normal physiology. Innate immune cell-derived pro-inflammatory cytokines and chemokines activate and recruit nonresident immune cells to the site of infection, thereby amplifying the inflammatory responses to clear infection or injury. This phase is followed by a cytokine milieu that promotes tissue regeneration. There is no absolute temporal distinction between these two phases, and cytokines may have dual pleiotropic effects depending on the timing of release, inflammatory microenvironment or concentrations. IL-22 is a cytokine with reported pro- and anti-inflammatory roles; in this review, we contend that this protein has primarily a function in restitution of normal tissue and physiology.