mRNA Vaccines for RSV, Flu, COVID-19 Could Change Immunizations Landscape

In an interview with Pharmacy Times, Francesca Ceddia, MD, senior vice president of respiratory vaccines at Moderna, discussed what the company is focused on for the future and how mRNA vaccines could change the treatment landscape for respiratory illnesses.

Aislinn Antrim: Hi, I'm Aislinn Antrim with Pharmacy Times, and I'm here with Francesca Ceddia, Senior Vice President for respiratory vaccines at Moderna, to discuss mRNA vaccines and the important research surrounding them right now. So, to kind of start off, what are current key areas of interest in respiratory vaccine development at the moment?

Francesca Ceddia, MD: Thanks, Aislinn, and it's a pleasure to be here. So, first of all, I would say that respiratory vaccines are a priority for Moderna because they address an important unmet need. There are lower respiratory tract infections that are quite a leading cause of death globally. And every year, approximately 1 million people die of lower respiratory tract infections. And, therefore, we have definitely prioritized this area. And currently, we are working on a number of respiratory viruses. But I would say the priority ones are COVID-19, RSV, and flu, of course. Yes, these are definitely the key areas for us.

Aislinn Antrim: So, a Data and Safety Monitoring Board recently endorsed the phase 3 portion of clinical trials for the mRNA RSV vaccine candidate. Can you discuss the earlier data supporting this phase 3 launch?

Francesca Ceddia, MD: Yeah, so before the starting of the phase 3 program, like for every vaccine, we make sure that we have all the necessary information to safely progress to a larger study. And the current phase 3 study which is ongoing for the RSV program is on approximately 34,000 individuals, because this trial is assessing the efficacy of the vaccine. And it's studying subjects who are vaccinated against it, the candidate vaccine versus subjects who are receiving the placebo control. And therefore, prior to that, of course, you do a phase 1, 2, and we studied several individuals, approximately 2000 individuals, in the phase 2 program, and we could see that the tolerability and safety profile was acceptable to progress. But also, interestingly, we noted the baseline titers. So, people who got vaccinated had baseline titers, including the placebo groups, which means that subjects had all encountered a previous RSV infection. However, after vaccination, when subjects were boosted with a dose of the vaccine, we could see a very strong immune response. And an immune response was against both the RSV, a component of the vaccine, and the RSV B strain. So that was quite reassuring. So, if you add the immune response, plus the new safety concern on the phase 1, 2 components of this study, the data safety monitoring board that was reassured basically to enable us to progress to the phase 3, which is currently ongoing.

Aislinn Antrim: Wonderful, that's definitely encouraging. For this RSV vaccine candidate specifically, what gaps in care would this vaccine fill?

Francesca Ceddia, MD: Yeah, it's interesting mainly because RSV vaccines have been studied for many years. There was an issue, though, with RSV vaccines. The protein that is the target for the vaccine, which is the F glycoprotein, is quite unstable. And the previous vaccine target used to have as a focus that post-fusion protein, but this post-fusion protein did not solicit neutralizing antibody titers. And then when it was understood, the big breakthrough was to understand that we could actually stabilize the confirmation of the protein and defining the pre-fusion component of the protein. It was an important finding. And that is what we have in our current RNA vaccine.

So, our vaccine encodes for the prefusion glycoprotein F, and it cross protects against the RSV A and RSV B component. Now, the important elements are there was a gap in terms of identifying the right vaccine candidate. And so, this new feature, this new discovery, has allowed us to make a major breakthrough in research, but also there is an important unmet need remaining. Currently today, there are no vaccines available, and the treatment is quite limited. And there are many, many individuals who are both at the extreme of ages, both in children, usually below 2 years of age, that are affected by RSV, but also older adults. Now, it is more known in the younger kids. So, if you think about RSV, I think a lot of mothers would think that their children have had an RSV during the life of their children when they were very young. But not many people know that actually RSV affects a lot of individuals who are above 60 years of age. So, older adults, and this is a cause of important lower respiratory tract infection that can have severe consequences, especially if people have also additional comorbidities, for example, they suffer have additional respiratory conditions.

Aislinn Antrim: Very interesting. Turning our attention to flu vaccines a little bit, attention is quickly shifting there for the upcoming season. And a phase 2 interim analysis of Moderna’s seasonal flu vaccine candidate found positive results. Can you review these findings?

Francesca Ceddia, MD: Yes, again, in every clinical trial we always look into the tolerability profile of the vaccine, and then we look into the immunogenicity. And this candidate vaccine, which we call 1010, mRNA 1010, has demonstrated to be well tolerated and with no major safety concerns. But also, it elicited an immune response which was higher for the influenza A [strain], and A was higher, meaning that it has the potential to add superior immune response to the currently available vaccines which are standard of care, and has the potential to have a non-inferior response to the standard of care for the B influenza strains. Now, it is important, particularly the A, because the A strains are the ones which are associated with the highest hospitalization rates, for example, everywhere around the world. So, this is very promising.

Aislinn Antrim: Wonderful. And how can mRNA flu vaccines offer new protection for patients and what does this approach change about flu vaccines?

Francesca Ceddia, MD: Well, first of all, we have to think that of the currently available [vaccines] there is an unmet need still in the influenza world. Because despite the fact that there are a number of vaccines available, the efficacy of this vaccine is not the greatest. You know, when you have a well-matched year for the influenza strain, you can get between 40% to 60% vaccine efficacy, which is not really super high efficacy. Thanks to the construct of the mRNA vaccine, we have the opportunity eventually to rapidly adjust. For example, if there is a mismatch in late season, this is something that you can do with mRNA because you can produce a vaccine very quickly, but you cannot really do that with a traditional vaccine. So, with traditional vaccines, it may take up to 6 months to develop the vaccine. For mRNA vaccines, you can do this in 3 to 4 months. So, that's a major, major advantage.

And the other thing, and this is what is in our pipeline and what we're trying to do, is having the potential to add additional strains, including additional antigens, like neuraminidase that are more conserved antigens and have the ability to drift less than the traditional antigens that are contained currently in the vaccines. So, speed, reliability of supply, [and] ability to include additional antigens are all advantages for the mRNA vaccines. And particularly, we believe that we have the potential to demonstrate superior responses, particularly, as I said before today, relative to the standard of care.