Hosted by the School of Biochemistry
Abstract: RNA-based vaccines have emerged as a highly attractive approach, demonstrating the ability to induce robust immune responses against COVID-19, coupled with rapid and relatively easy production methods. Preclinical studies suggest that self-amplifying RNA (saRNA) vaccines may offer additional benefits, including: self-replication, enabling exponential antigen expression; equivalent protection at lower doses compared to mRNA vaccines; and prolonged antigen expression in vivo. However, early clinical trials have shown that saRNA vaccines fall short of the potency achieved by mRNA vaccines in humans, particularly in inducing de novo immune responses. Despite this, saRNA holds promise as a low-dose booster strategy. Clinically evaluated saRNA platforms are primarily derived from alphavirus positive-strand RNA genomes, where the viral structural proteins are replaced with a gene of interest (GOI). The retained non-structural proteins, which encode the replicase, enable antigen amplification through RNA self-replication. However, these native viral sequences evolved to support transmission between mosquitoes and rodents, with human infection being rare and not associated with onward transmission. The gap between high potency in small animal models and moderate efficacy in humans likely reflects the lack of RNA genome adaptation to the human biological context. This presentation will review the status of saRNA technology, lessons learned from clinical trials, and how recent insights into RNA genome modifications could enhance the potential of saRNA as a next-generation platform for human vaccines and therapeutics.
Robin Shattock is Professor of Mucosal Infection and Immunity at Imperial College, London with over 30 years’ experience in research and development of vaccines and anti-infectives. The focus of his research is the development of vaccines to prevent pandemic threats and poverty related diseases. His current academic research portfolio includes vaccine projects on SARS-CoV-2, HIV, Ebola, Lassa fever, Marburg, Rotavirus and Rabies viruses, Chlamydia Trachomatis, Streptococcus A, and Yersinia pestis. He leads the Future Vaccines Research Hub based at Imperial with manufacturing partners in UK, Bangladesh, Vietnam, and South Africa. Robin has a strong track record of translation research having taken a wide range of vaccine products through from discovery into clinical testing. His research group was the first in the world to publish on clinical trials of a self-amplifying RNA vaccine against SARS-CoV-2. He is an elected fellow of the Academy of Medical Sciences.