Q&A: Will Moderna's mRNA RSV vaccine increase uptake next respiratory virus season?
Click Here to Manage Email Alerts
Key takeaways:
- There are now three FDA approved RSV vaccines.
- This marks the first mRNA vaccine approved by the FDA for the prevention of a disease other than COVID-19.
In late May, the FDA announced approval of Moderna's mResvia, a messenger RNA vaccine to protect adults 60 years or older from lower respiratory tract disease caused by respiratory syncytial virus.
This marked the third vaccine approved for respiratory syncytial virus but the first time mRNA technology was used for preventing a disease other than COVID-19. The company said at the time of the approval that it expects to have mResvia available for eligible populations in the U.S. within the next year.
With three RSV vaccines now available and low uptake reported during the last RSV season — the first season that any RSV vaccine was approved and available — there are questions surrounding what this approval could mean for the upcoming RSV season.
We spoke with David O. Freedman, MD, professor emeritus of infectious diseases at the University of Alabama at Birmingham, and Ryan C. Maves, MD, professor of medicine and anesthesiology at Wake Forest University School of Medicine, about what impact the vaccine could have and what else could be done ahead of RSV season to improve vaccine uptake.
Healio: How does Moderna’s mRNA vaccine compare with the other two RSV vaccines? Is it more effective? What do the trial data show?
Freedman: Moderna has a completely different mechanism because it is mRNA-based, meaning that after injection the person’s body makes the protein to stimulate the immune system. This is exactly the same design and configuration as Moderna’s COVID-19 vaccine. With Pfizer and GSK (both adjuvanted), the recombinant protein is injected directly in a more classic vaccine formulation. GSK’s vaccine is based on an RSV preF3 protein whereas Moderna and Pfizer’s vaccine is based on a PreF protein.
It is difficult to compare the three vaccines directly because the trials for each were done very differently with different endpoints and different periods of follow up after vaccination. The definition of mild and severe disease differed between trials, the age groupings for which vaccine efficacy (VE) was calculated differed. Prevention of hospitalization and death have yet — before the Advisory Committee on Immunization Practices June meeting — been reported in real life.
In terms of prevention of significant disease (excluding hospitalization) in the short term (4 to 8 months after vaccination), Moderna appears roughly equivalent to Pfizer and GSK. Moderna is expected to present, for the first time at ACIP, second season data after a single shot, which is already known for Pfizer and GSK to be reasonably good.
Maves: The initial trial data published in The New England Journal of Medicine showed about 68% efficacy against all-cause RSV infections and 84% efficacy against lower respiratory tract infections, like pneumonia.
In terms of lower respiratory tract infections, this is relatively similar to the data published for the two earlier vaccines and might be a bit better than the bivalent vaccine produced by Pfizer. The incidence of severe disease in the Moderna trial was relatively low, but there seems to be good protection provided.
Healio: It uses mRNA technology, which was so effective for COVID-19 vaccines, but there has been a lot of vaccine hesitancy surrounding the mRNA COVID-19 shots. Will the addition of an mRNA vaccine for RSV have a marked effect on RSV vaccine uptake?
Freedman: Two issues may play against Moderna mRNA: First, people do remember the short-term local effects — day or two of fever, malaise, etc. — with mRNA COVID-19 vaccines, even if no comparison of side effects of the three RSV vaccines have been done, and second, mRNA vaccines are perceived to be short lived because of all the boosters that have been recommended with COVID, so Moderna really needs strong second-season data to prove this is not an issue with their RSV vaccines when it is known that Pfizer’s and GSK’s vaccines last for two seasons.
The advantage for Moderna’s RSV vaccine is that the trials so far have shown an excellent safety profile — no deaths, no severe adverse events and no Guillain-Barre (GBS) syndrome, no cardiomyopathy in 20,000 subjects who received actual vaccine in the trial.
This is in contrast to the very real GBS safety signal seen in real life with Pfizer’s and GSK’s vaccines.
Maves: It is worth recalling that over 80% of U.S. adults have received at least one dose of an mRNA vaccine, with well over 90% of those over the age of 50 years. So, we shouldn’t overstate the importance of vaccine hesitancy regarding mRNA vaccines. I think that having a third option is a good thing, and I suspect the number of people who will avoid RSV vaccines solely because of mRNA technology are probably not likely to pursue RSV vaccines in general.
Healio: The ACIP is set to vote later this month on new RSV vaccine recommendations for adults. Should members vote to strengthen the language used last year when it said older patients “may receive” an RSV vaccine rather than saying they “should” receive one? Would this improve vaccination rates?
Freedman: Last year they did the "may receive" recommendation for GSK and Pfizer mostly because unclear safety data and inability to calculate risk/benefit, re: GBS adverse effects. Robust, but still incomplete, real-life GBS data have been published and more may be presented on June 26. It is clear that a small amount of excess GBS risk (5.0/million vaccinees — well above population baseline) exists for Pfizer, much less for GSK (1/million) and zero so far for Moderna (no real-world data yet).
At the February ACIP meeting, detailed calculations were shown that the benefit of the vaccine far outweighs this GBS risk, but that is sometimes hard to sell to the public, especially in cohorts of people at less risk of severe complication because of relatively young age or no comorbidities.
Maves: I would certainly favor stronger language while still allowing for shared decision-making. That being said, I appreciate that this is fundamentally a semantic question, and I respect the judgment of the ACIP panel regarding the precise phrasing they think is most appropriate. Providing guidance that protects those at risk while respecting autonomy and the clinician-patient relationship is a tricky balance.
Healio: Are you hopeful that RSV vaccination will catch on eventually?
Freedman: Yes, of course, but we still need more real-life efficacy data to better define the real risk groups who benefit the most and make stronger recommendations a bit more selectively for those people rather than a vaguer and weaker recommendation for everyone above a certain age.
Maves: I am, but it will probably take a while.
Healio: The ACIP recommendation last year was based on just one season of data from the first two RSV vaccines, which was cited as a reason for the softer recommendation. Since then, researchers reported two seasons of data for GSK’s vaccine during IDWeek — it had a sustained effectiveness of around 67% among older adults — and Pfizer reported topline data in February that showed its vaccine’s efficacy declined from season one to season two, but remained around 78%. Have these new data impacted how you see the vaccines?
Freedman: These VEs are aggregates in a large number of persons older than 60 years, most of whom are at the younger end of the cohort and many in otherwise good health, and the endpoints are clinically significant disease but not for rates of hospitalization, ICU care or death. Still overall, the vaccines will save lives and prevent hospitalizations, but it is also very clear that the benefits of prevention in these most severe endpoints really take off in persons older than 75 years, people in nursing homes, etc.
I still see us needing very specific risk-based recommendations based on data and not models to focus our targeting efforts, especially if discussion with the treating clinician remains part of the recommendations.
In February, an ACIP slide stated “the extent to which effectiveness will extend to older adults at highest risk of severe RSV (older than 75 years, frail, immunocompromised) is still unknown. To be clear, very little data on those older than 75 years exist, and this age group certainly will not respond to any vaccine of any kind with the same robustness as even those aged 65 years.
Maves: Not really. If anything, it is reassuring. The open question is what happens after 2 years and whether there will be a need or a benefit to future doses, say 5 years in the future.
Healio: Are there still data that you would like to see that haven’t been published?
Freedman: As per above,VE against death, hospitalization, ICU care especially in persons older than 75 years but also in younger groups. Also, data on RSV rates in foreign travelers — particularly cruise ship passengers and group tours (on buses all day) because both COVID-19 and influenza are such problems in these groups.
In fact, if we are already defining high-risk factors for RSV (per current ACIP guidelines) as persons in congregate settings such as nursing homes and institutions, it would seem intuitive to add cruise ship passengers, many of whom are quite elderly, and tour group members right away at this meeting to the high-risk group.
Maves: I care for a lot of patients with transplants or hematologic malignancy, two groups that are at markedly increased risk of severe RSV infection but who were not really represented in the existing clinical trials. These are the groups for whom I really want to see vaccine efficacy data. I would also be interested in looking at younger adults with significant underlying cardiac or pulmonary disease.
Healio: What’s the No. 1 thing that could get RSV shots into more arms this year?
Freedman: A well-publicized RSV outbreak on a couple of massive cruise ships or a massive spike in RSV cases and deaths after the Thanksgiving holiday to sensitize people before the Christmas holiday.
Maves: Awareness and advocacy. Public health authorities have to make patients and physicians aware of these vaccines and their indications, and then physicians and other clinicians need to be advocating for their use in our patients. Despite the general decrease in faith in public health authorities among the public in the wake of the pandemic, people still trust their doctors.
Healio: Who is ultimately responsible for increasing vaccine uptake: physicians or public health agencies like the CDC?
Freedman: Public health agencies are still suffering from credibility issues, some which are politically driven since COVID-19, and patients who have an ongoing relationship with a primary care provider trust that provider’s advice at the point of care more than anything else. Still, it is the responsibility of public health to convincingly educate the providers as a priority.
In 2023, there was too short a time window to educate providers and too little convincing data, so that many providers did not bother to incorporate RSV vaccine into their daily primary care routine.
Maves: I think that’s a false dichotomy. It’s like asking who is responsible for a safe airline flight, the ground crew or the pilots? Clearly, it is both. We all have a part to play.
References:
- Moderna receives U.S. FDA approval for RSV vaccine mRESVIA(R). https://investors.modernatx.com/news/news-details/2024/Moderna-Receives-U.S.-FDA-Approval-for-RSV-Vaccine-mRESVIAR/default.aspx. Published May 31, 2024. Accessed June 12, 2024.
Collapse
Healio Interviews
Click Here to Manage Email Alerts