At GSK, we work on vaccines aiming to help combat devastating infectious diseases like malaria, tuberculosis, HSV, RSV and COPD. Jeff Ulmer, Head Preclinical R&D US, Vaccines at GSK, explains how synthetic Self-Amplifying mRNA (SAM) and ground-breaking partnerships may help us fight more conditions faster and more efficiently than ever before.
Traditionally, scientific breakthroughs that change the way we understand and treat diseases often happen only once in a lifetime, sometimes even less. In my 40 years of working in scientific research I have seen great advances in the vaccine research and development, but I’ve never felt as close to a revolutionary breakthrough as I have in our current work in vaccines.
Today, our new technological capabilities allow us to intervene in biological interactions between our body and pathogens, which not only creates the potential for significant benefits for patients, it opens opportunities in many new disease areas, optimises the use of production facilities, and could help us make potent vaccines in a fraction of the typical development timeframes.
Self-replicating mRNA (SAM) is a technology that can help to make effective vaccines more quickly. Here, Jeff Ulmer explains how SAM could disrupt the way we make vaccines.
GSK has a long history and expertise in the development of vaccines with state-of-the-art technologies, such as self-amplifying messenger RNA, or “SAM”. This particular technology has the potential to radically revolutionise the way we make vaccines. It combines the knowledge we have accumulated over the past 25 years on nucleic acid vaccines to deliver more and potentially more effective vaccines against a broader range of conditions, faster and more efficiently than ever before using a relatively simple chemical process. To begin developing a SAM-based vaccine , GSK’s scientists design a SAM molecule synthetically in a laboratory, using portions of the genetic code of a virus. However, in the SAM molecule, the genes linked to the virus’ ability to cause infection are being deleted[i], and replaced with genes from target viruses that will produce the antigens for desired vaccines.
Once injected in the body, SAM molecule self-amplifies and uses the mechanisms of the body’s own cells to produce the antigens of the disease pathogen. These antigens mimic an early-stage infection and trigger the body’s immune response, generating immune memory for future protection against the pathogen, but without causing disease. The human body becomes the factory for its own vaccine.
Owing to its self-amplification and built-in adjuvant properties, SAM can produce sufficient viral antigen to create a strong and sustained immune response, without the need for additional substances which enhance the body's immune response to the antigens used on the vaccine.
Using the body’s own cells to produce the vaccine means that GSK would only be producing the SAM genetic platform and its delivery systems. Volumes may be much smaller than with traditional vaccines and the production process would be very similar for a broad variety of different vaccines, potentially leading to substantial streamlining of the vaccine R&D process.
With SAM technology we will be able to produce many different vaccines against very different pathogens using the same processes, in the same factory. Eventually, we could even produce vaccines in mobile labs as small as trucks, which would expedite our response to disease outbreaks around the world.
Pre-clinical research for SAM technology has shown potent and robust protective immune responses against various pathogens including viruses, bacteria and parasites.[ii]
By mid-2020 we expect the results of our first Phase I clinical trial of SAM in rabies, which is a benchmark model against a vaccine known to be immunogenic and protective in humans.
SAM could be the first step in a real revolution for vaccines and in healthcare that GSK is proud to lead. We’re committed to achieving more breakthroughs like SAM against the world’s outstanding medical challenges. We’re eager to extend the value of vaccines to more people and different unmet health needs around the world. This kind of innovation is a novel way that helps us to progress towards a healthier, more productive world.
[i] Ulmer JB et al. Expert Opin Drug Discov 2015;10:101–106
[ii] Hekele A et al. Emerg Microbes Infect 2013;2:e52
This blog is part of our A view from the lab… series, sharing insights from scientists around our company. It was originally published on Jeff's LinkedIn profile
