Moderna makes mRNA mpox vaccine

The pharmaceutical company Moderna, who were responsible for one of the mRNA-based Covid jabs developed during the pandemic have now gone on to use this same technology to develop a vaccine against the mpox virus that is causing the current outbreak of mpox in the Democratic Republic of the Congo. Yes there are already vaccines against emerging disease, but they’re in short supply, and they’re more difficult to update if the vaccine needs to change. Indeed, UNICEF - which is the UN’s children’s agency - recently issued an emergency tender for the procurement of more mpox vaccines. Galit Alter is Moderna’s vice president of immunology research…

Galit - The current vaccine that we do have that is licensed for global use, this JYNNEOS vaccine, does provide a hundred percent protection against death in the context of preclinical models and has been shown in clinical trials over the last few years to provide protection also in humans in reducing disease and pathology. And so we do have an incredibly robust tool currently out in the world that is able to curb the potential threat caused by the monkeypox virus. I think the question that we're trying to ask here is, you know, does this additional technology that we now have that can pivot and potentially create vaccines in an accelerated timeline that we know is safe and that we know is highly immunogenic and could potentially focus the response in a more deliberate way because of the way that it trains the immune system? Could this technology help fill a gap in our future response to monkeypox or to other pandemic threats? And so I think what we're trying to understand is really how do we fit in the current world where there is a particular vaccine out there where we can potentially fill those needs that might emerge with time as this virus potentially spreads more aggressively or changes with time.

Chris - How do you pick what to put into your vaccine? Because the way your vaccine works is that you are taking the genetic code that corresponds to a particular part of the virus. So how do you pick that bit of the virus we're going to put into the vaccine?

Galit - Well, that's a really important question and so I think the first thing I always try to explain is that nothing we do is done in isolation. Everything that we do in the context of these pandemic threats is done in collaboration with experts in the field that have been studying these viruses for decades throughout their careers. And so what we did really immediately upon taking on this challenge for monkeypox is to essentially create collaborations with credible figures in the pox viral world who had been studying viruses and understanding which particular components of the virus are the most important targets for protection against disease and infection. And what they had learned over those decades of research that they had been conducting in the laboratory in their animal models was that just four surface proteins that sit on the outside of the virus is really all you need to attack with an immune response in order to prevent the virus from gaining entry into human cells. And what we focused on then, for the next year or so in the laboratory, is working the design these particular proteins so they could express effectively off of our vaccine technology, this genetic code that we essentially deliver to the immune system to actually make sure that when the immune system sees these proteins, they see them in a context that is absolutely perfect to raise immune responses. So we took these designer proteins that we expressed off of our genetic vaccines, and we delivered them into mice. We then challenged these animals to the monkeypox virus. And what we're surprised and elated to see was that this novel technology was able to raise responses and essentially control the virus with an exquisite capacity, both limiting the ability of the virus that caused death, but also really helping to diminish the amount of disease that these viruses can cause within these animal models.

Chris - And when you put this into the body or an experimental mouse, for example, does it make antibodies against those bits of the surface of the virus? Or does it make white blood cells, T cells, that can hit virally infected cells? Or does it do both?

Galit - The beauty of the Moderna mRNA vaccine technology is that we are able to raise both these white blood cell responses that are critically important for helping the immune system to make many, many antibodies that can both block the virus from infecting a future cell, but also to recognise the virus when it's floating around and rapidly clear it from the system, preventing it from causing any further infection or disease.

Chris - What's the longevity of the response like? Because we know that with things like the existing vaccinia based vaccines, the old fashioned way that Edward Jenner would recognise, those tend to be lifelong, those protective effects. Do you think you'll get lifelong protection with this Moderna construct or do you think we'll be going back giving people boosters?

Galit - That's a really important question. With the mRNA vaccines, what we saw in the COVID-19 pandemic is that we saw these very robust immune responses that did decline to some level. But if you look at some of these long-term studies that were done in large populations of vaccinated individuals, what we saw is that this technology really is generating immune responses that can last for a very, very long time. But also importantly, this technology also raises those white blood cells that you mentioned that essentially live for very long periods of time, constantly surveying our body for potential entry of a pathogen. And so we have this long-term immunity built in really both through these white blood cell responses as well as by antibodies that we hope that this novel vaccine technology can help to serve or to fill the gaps for other technologies that are out there.

Chris - How long is it going to take you to get this to market? So you've got something that's regulator approved that could be deployed into the field? Because obviously the crisis we're having is now and we need this sort of solution now.

Galit - Right, so it's important to just mention that this vaccine has not been approved by regulators. We're right now in the middle of a phase one, phase two trial. When in those trials, our goal is to go into healthy populations and ask, are these vaccines safe. With that data, understanding whether we are inducing robust immune responses as well as seeing that these vaccines are incredibly well tolerated at a population level, gives us the essential information that we need then to make decisions about how we can move forward in the context of a licensure trial or commercial deployment.