Researchers have been studying mRNA for decades, and it wasn’t until the COVID-19 pandemic that the platform found its greatest use in vaccines. Moderna is a leading research and development company in this field. In its simplest terms, the company explains that there are a few steps that can be taken to fight different diseases and viruses and the process can be repeated over and over again. The company explains that mRNA-based vaccines and therapies begin by identifying a protein designed to prevent or treat a certain disease.1 Their researchers then design an mRNA that carries instructions for this protein that could help the body fight infection or prevent disease.1
Armed with this knowledge, Moderna has invested in this platform to combat multiple diseases and viruses.
At Moderna’s Vaccine Day in late March, the company said its mRNA platform could transform the vaccine market because of the technology’s ability to develop candidates faster, combine vaccines and target vaccines. difficult viral targets.
“We believe our mRNA platform is disrupting the traditional vaccine market and, as outlined in our Vaccine Day announcements, we plan to bring many more safe and effective vaccines to market,” said Stéphane Bancel, Director General of Moderna. “There is an opportunity for Moderna to have a positive impact on public and global health, and with 31 active development programs, including 19 in the clinic, we plan to address several critical unmet medical needs through the power of our mRNA platform.
Moderna expects to be in a Phase 1 trial this year for its combination flu and COVID-19 vaccine, mRNA-1073. In terms of long-term strategy, the company is considering the annual administration of combination vaccines like mRNA-1073.
The company also said it was developing its mRNA-1230 vaccine to cover SARS-CoV-2, influenza and respiratory syncytial virus (RSV) as well as another candidate, mRNA-1287, for human coronaviruses. endemic.
In an extensive interview with ContagionSunny Himansu, MBBS, DSM, Associate Director, ID Bacteriology, Infectious Diseases, Moderna, provides an overview of the mRNA platform, the role of mRNA therapies, and where they stand with some of their experimental vaccines.
Contagion: Thinking about the mRNA platform, what about the technology that allows it to be developed for use against multiple disease targets?
Himansu: The mRNA platform is extremely versatile as it provides instructions for the body to make proteins capable of performing a wide range of functions. For example, mRNA vaccines train the body to fight infection by providing the instructions to make key building blocks of specific pathogens, as we did with our COVID-19 vaccine. Therapeutics based on the mRNA platform can help the body make a missing protein or replace a faulty protein that leads to disease, among many possible applications. Many defects or targets that were beyond the reach of traditional modes of treatment may be amenable to treatment with mRNA-based therapies.
Moderna’s mRNA technology platform works much like an operating system on a computer, and each interchangeable mRNA sequence is like specific, interchangeable software. Today, we can create these vaccines and drugs quickly and deliver them to the right place in the body with great efficiency. This will open up new ways to prevent and treat a wide variety of diseases, from latent viral infections to cancer and rare diseases.
Contagion: Speaking of multiple targets, the company is developing a unique combination vaccine to cover SARS-CoV-2, influenza, and RSV. Can you tell us when you will be in a phase 1 clinical trial for the experimental vaccine and do you consider it an annual vaccine given at the start of the flu season?
Himansu: Our combined SARS-COV-2/Influenza/RSV (mRNA-1230) vaccine is currently in preclinical development. We are clinically testing the different “pieces” of this combination vaccine in parallel and have shown in preclinical mouse models that the combination vaccine induces a robust antibody response to all antigenic components in mice. We look forward to progressing with a Phase 1 program and aspire to administer this vaccine seasonally.
Contagion: Can you provide an overview of the 2 HIV vaccines Moderna has in development and how they target HIV?
Himansu: A protective HIV vaccine will likely need to produce broad neutralizing antibodies or bnAbs capable of neutralizing a wide range of HIV variants. Moderna is working with leading experts in the field of HIV vaccines to develop a vaccine regimen that will produce these antibodies in humans. Currently we are optimizing different antigens in 2 different clinical studies.
The mRNA-1644 or G002 study tests vaccine antigens that target B cells to produce broadly neutralizing antibodies (bNAbs). As part of the study, we will sequentially administer 2 mRNA vaccines designed by a team of researchers from the International AIDS Vaccine Initiative and Scripps Research. These immunogens (antigens that trigger an immune response) are designed to promote the early maturation of specific types of B cells into cells that produce bNAbs against HIV.
The mRNA-1574 or HVTN302 study will test 3 different forms of HIV env trimers encoded by mRNA, the only protein on the surface of the HIV virus required for entry into human cells. The objective of this trial is to identify the best trimer design that can be used in a future clinical study to obtain bnAbs by the sequential vaccination of multiple antigens.
Contagion: Why the decision to pursue 2 vaccine strategies?
Himansu: Finding a protective HIV vaccine has been an elusive target; however, recent clinical studies have shown that bnAbs may be protective in humans. With the goal of designing a vaccine that elicits bnAbs through vaccination, we are trying to strategically design parallel clinical studies to address certain hypotheses that may ultimately accelerate the development of a successful candidate to market.
Contagion: At Moderna’s Vaccine Day, the company talked about its mRNA design studio. Can you give an overview of it and how it can be used with potential external partners?
Himansu: Our mRNA Design Studio is proprietary web-based software that enables rapid design of multiple mRNAs for research and testing within days. Our in-house suite can design mRNAs suitable for any protein in the human genome, or novel or designer fusion proteins for various applications. Cloud-based computation then optimizes this sequence based on bioinformatics algorithms.
Finally, our digital control platform ensures the transmission of sequences to our synthesis robots for mRNA production. Moderna aims to use our Design Studio as an engine to accelerate both basic research and the search for new drug candidates for clinical trials in partnership with scientists and biopharmaceutical players.
Contagion: With respect to your COVID-19 vaccine and the development of emerging variants, how would you characterize Moderna’s ability to update its vaccines to address new strains?
Himansu: One of the biggest advantages of our mRNA platform is the speed and efficiency with which we can integrate new mRNA sequences. We have already designed and integrated a new version of the COVID-19 vaccine for the specificity of Omicron variant mutations and we are testing it in phase 2 booster studies in combination with our COVID-19 vaccine. Our platform will be able to quickly respond to future emerging variants of concern with additional multi-purpose boosters.
Contagion: Moderna is using the mRNA platform to develop vaccines and has treatments in early development, do you see the therapeutic side of the business as a vital part of the business?
Himansu: The elegance and adaptability of mRNA-based drugs makes them an ideal platform to harness the body’s own system for therapeutic approaches in key disease areas and is a critical focus for the company. To this end, we are developing therapeutic vaccines tailored to the emerging field of immuno-oncology to produce personalized cancer vaccines that can help the patient’s immune system better recognize cancer cells as foreign and destroy them. Moderna also recognizes the need to treat the more than 7,000 rare diseases that affect more than 300 million people worldwide with treatment options that are not currently available.
Finally, we are developing several potential mRNA therapies that have the potential to attenuate autoimmune activation and help restore proper immune function in people with devastating autoimmune diseases.
1.The power of mRNA. Modern. Accessed May 15, 2022. https://www.modernatx.com/power-of-mrna/modernas-mrna-platform