By Greg Kulnis – Vice President, Customer Solutions (Infectious Disease) for Nexelis
The Covid-19 pandemic has led to unprecedented collaboration and acceleration in vaccine development. In the past two years, many leading pharmaceutical and biotech companies have shifted their research and development (R&D) focus to tackle the threat of SARS-CoV-2. Companies have needed to rapidly pivot, establish new research teams, and invest in new technologies and platforms in the race to find an efficacious vaccine or treatment process.
Some of the greatest successes in this shift have come from the use of messenger RNA (mRNA) technology. The development and approval of the Moderna and BioNTech-Pfizer mRNA vaccines were firsts in infectious disease, and the success of this approach for these companies means others are now following suit in the hopes of applying the technology to other diseases. The potential is evident, but the use of mRNA could change the paradigm of vaccine R&D altogether – so what do industry stakeholders, from clinical researchers to regulatory bodies, need to do to keep up?
A brief overview of mRNA vaccines
While traditional vaccines contain a weakened or inactivated virus, or some component of a virus or bacterium, mRNA vaccines trigger the body to have our own cells make a protein that corresponds to the virus to elicit an immune response. The outcome is the same – the vaccination offers protection from the virus without the risk of potentially serious consequences of getting sick.1,2
Researchers have been studying and working with mRNA vaccines for decades, particularly in the field of oncology. However, although there are dozens of live trials testing mRNA vaccines in various cancer indications, including pancreatic, colorectal and melanoma, there have been no approvals for these approaches to date.
A major factor in the delay of realising the potential of mRNA vaccines has been one of biology. mRNA is inherently unstable and therefore perfecting delivery to the body has been a challenge for researchers – with many struggling to find the right formula of fats and nucleic acids (the ‘building blocks of mRNA vaccines’) necessary for transferring the mRNA into cells.
As of today, though, the renewed focus on, and investment in, mRNA approaches due to the Covid-19 pandemic means we have the world’s first mRNA vaccines approved in infectious disease, with many more candidates in development for diseases such as rabies, yellow fever, respirational syncytial virus and influenza.
Adapting for mRNA vaccine development
Key differentiators of mRNA-based vaccines are their simplicity, and the speed at which they can be developed once the genetic sequence of the virus has been established, given the right R&D environment.
From a classical immunological assay perspective, mRNA vaccine R&D is not significantly different from a traditional vaccine development approach. The optimal R&D process will introduce in vitro assays for immunogenicity at early phases to help support lead candidate selection as well as in vivo models for immunogenicity, reactogenicity and efficacy.
It is the speed and scale at which mRNA vaccines can be developed that bring new challenges, including the need for large volumes of key reagents, produced quickly. As well as providing expertise in producing the materials themselves, partnering with the right CRO will ensure sponsors have access to the necessary testing capacities and the agility to address issues, such as changes to formulations, to capitalise on the advantages of the technology’s simplicity and the condensed development timelines.
Furthermore, stakeholders involved in mRNA vaccine development, from manufacturing through to inoculation, need to adjust to working with a cold chain which can pose challenges for clinical trial operations. Due to the instability of the RNA, mRNA vaccines must be stored below certain temperatures to maintain their efficacy. This adds a layer of complexity, not to mention expense, compared with traditional vaccines.
The future’s bright…
As the journey to develop further mRNA vaccines gets underway, sponsors will need to address how they can make a case for one vaccine compared with another in such a busy space. There will be a need to develop a standard set of R&D/preclinical assays early on, enabling comparison between candidates as well as against the required baseline immunogenicity response, to identify lead candidates to progress to Phase I studies.
These vaccines will also generate high volumes of data, and there will be a need for non-inferiority studies to gain a significant market share. Positive data can offer a clear path to approval; however, there will be significance in developing an effective value-based story for an individual vaccine that will make sense to regulatory bodies. Longer term, the development of a focused set of standardised assays for sponsors, across markers including durability and breadth of response, could allow for more accurate comparisons between candidates and ultimately more informed recommendations from regulators.
We may still have a way to go to fully realise the potential of this technology, but the Covid-19 pandemic has certainly paved the way, both in demonstrating the viability of mRNA vaccines and in kick-starting a new level of investment and interest in the field. There is no doubt this interest in utilising the technology across multiple fields – from oncology to infectious disease as well as rare or orphan diseases – will continue to grow. It will certainly be exciting to see the potential rewards in the years to come.
References
1: Centers for Disease Control and Prevention. Understanding mRNA COVID-19 vaccines. Available at: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/mrna.html. [Last accessed: May 2022].
2: MedlinePlus. What are mRNA vaccines and how do they work? Available at: https://medlineplus.gov/genetics/understanding/therapy/mrnavaccines/. [Last accessed: May 2022].
Author Bio
With nearly 20 years of experience in vaccines and assay development, Greg has held several different roles ranging from clinical bench testing to Life Sciences sales. With extensive expertise in pharmaceutical development, Greg leads global teams in operational needs identification through solution development. Spanning R&D, pre-clinical and clinical support, Greg supports the development for infectious disease prophylaxis and therapeutic modalities. Currently, Greg serves as the Vice President, Customer Solutions (Infectious Disease) for Nexelis, a Q2 Solutions Company.
