Grant: Project Grant

In 2024, an estimated 60,000 individuals in Canada were living with HIV, highlighting its ongoing global threat. Despite decades of research, an effective HIV vaccine remains elusive. Broadly neutralizing antibodies (bNAbs) represent a promising strategy for HIV prevention, as they can inhibit most viral strains from infecting human cells. However, inducing bNAbs through vaccination has proven challenging due to the complex affinity maturation process required, with current vaccine candidates failing to elicit the necessary immune response. Our project seeks to leverage the groundbreaking advances in RNA vaccine technology, exemplified by the rapid development and success of COVID-19 vaccines, to pioneer a novel circular RNA (circRNA) vaccine targeting HIV. This innovative approach aims to instruct the body to produce bNAbs against HIV-1 by designing circRNAs that encode two germline-targeting HIV-1 immunogens, delivered via specially engineered lipid nanoparticles with immunostimulatory properties. This multifaceted strategy addresses three critical aspects of vaccine development simultaneously: multiplexed immunogen design, enhanced germinal center immune responses, and optimized immunogen delivery kinetics. This project has the potential to significantly advance the development of effective HIV-1 vaccines while expanding our understanding of RNA vaccinology. As a versatile platform technology, it could catalyze Canadian innovation in next-generation vaccines for a wide range of emerging viral pathogens. Moreover, this work will bolster Canada's pandemic preparedness, strengthening the nation's capacity to respond swiftly and effectively to future global health crises.