Chikungunya virus (CHIKV) is an increasing burden to public health, with one billion people living in areas where mosquitoes transmit the virus. Unlike many mosquito-borne viruses, CHIKV is highly symptomatic and most infections result in joint swelling, muscle pain, headache, nausea, fatigue and rash. The name chikungunya describes the appearance of swollen joints and is derived from a word in the Kimakonde language meaning to become contorted. This virus is rapidly expanding geographically and increasing in severity, with recent outbreaks associated with neurological symptoms and long-term disability. As we lack vaccines or specific treatments, it is urgent that we develop new strategies to mitigate and treat CHIKV disease.

Like all viruses, CHIKV relies on the infected host cell and utilizes many cellular components and processes to complete its life cycle. This reliance can be exploited to uncover new antiviral targets, or to prevent CHIKV transmission by mosquitoes. One key step in the virus life cycle is the translation of viral genes into proteins. Indeed, many viruses manipulate host cell translation to favor their own life cycles. However, we lack a holistic understanding of how CHIKV subverts key RNA molecules for translation, and how mosquito and human cells fight back. This proposal aims to address this knowledge gap. The overarching goal is to better understand the interplay between CHIKV infection, host cell translation, and host cell defenses. Ultimately, this understanding can open doors for new mitigation strategies against CHIKV, an emerging mosquito-borne virus with devastating impacts on human health.

Tuberculosis (TB) continues to rank among the leading causes of mortality worldwide, with millions contracting the disease every year. Existing TB vaccines show limitations, notably in their efficacy in adults and in preventing pulmonary infections. This project proposes a novel strategy to bolster defenses against TB by optimizing vaccine delivery to the mucosal surfaces of the airways. Our interdisciplinary team is developing an innovative intranasal vaccine that leverages the latest in mRNA technology, specifically designed to combat TB. This vaccine employs Lipid Nanoparticles (LNPs) engineered to precisely target the delivery of mRNA vaccines to the airways where TB infection begins. This cutting-edge approach seeks to amplify the vaccine’s efficacy at the critical point of TB entry, enhancing the body’s immune response directly within the respiratory tract. The vaccine’s mechanism instructs the immune system to recognize and fight TB bacteria more efficiently, reinforcing respiratory defenses. This collaboration is a first for us and brings together diverse expertise from across the University of Toronto to address a critical challenge in infectious disease research. If successful, this project could lead to a new generation of TB vaccines that are more effective, easier to administer, and capable of offering protection where current vaccines fall short. Beyond TB, our work could open doors to similar strategies against other respiratory diseases, significantly impacting public health worldwide.