— Whether it provides lasting protection remains to be seen
Katherine Kahn, Staff Writer, MedPage Today
December 13, 2023
Moderna’s mRNA-based RSV vaccine was effective at preventing RSV-associated lower respiratory tract disease in adults ages 60 and older, according to results of the randomized ConquerRSV trial.
The mRNA-1345 vaccine was 83.7% effective (95.88% CI 66%-92.2%) in preventing RSV-associated lower respiratory tract disease with at least two signs or symptoms, and similarly effective (82.4%) against lower respiratory tract disease with at least three signs or symptoms (96.36% CI 34.8%-95.3%), Eleanor Wilson, MD, of Moderna in Cambridge, Massachusetts, and colleagues reported in the New England Journal of Medicine.
Participants who received the mRNA-1345 vaccine reported more systemic adverse reactions than the placebo group (47.7% vs 32.9%); the most common were fatigue, headache, myalgia, and arthralgia. Serious adverse events occurred in 2.8% of the participants in both groups, and most reactions were mild to moderate in severity and were transient. Fewer than 0.1% were reported to be related to the shot.
“This phase II-III efficacy trial showed that a single 50-μg dose of the mRNA-1345 vaccine in adults 60 years of age or older was efficacious against a spectrum of RSV-confirmed respiratory disease. No safety concerns were evident,” Wilson’s group concluded from following the participants for over 3 months.
Topline results of ConquerRSV had been announced in January 2023. “At that point, we knew that the trial met both its primary efficacy endpoints. Today’s publication provides further analysis of these data and trial design and affirms that the vaccine was generally well-tolerated in this population,” Wilson told MedPage Today in an email.
The mRNA-1345 vaccine was based on the same mRNA vaccine platform used to develop the SARS-CoV-2 vaccine, the authors wrote. It uses a preF antigen-based approach similar to the two non-mRNA vaccines recently approved for RSV. This approach was chosen because the preF conformation is the primary target of RSV-neutralizing antibodies and is highly conserved across both RSV subtypes.
“An important consideration will be how much protection an mRNA vaccine provides during subsequent RSV seasons and whether subsequent boosting will be appropriate,” Angela Cohn, MD, and Aron Hall, DVM, MSPH, from the National Center for Immunization and Respiratory Diseases at the CDC in Atlanta, wrote in an accompanying editorial. “Such questions about duration of immunity, along with reactogenicity and cold-chain considerations, remain important areas for further evaluation in the implementation of mRNA vaccines.”
“Although no cases were reported among adults 80 years of age or older in the current analysis, efficacy was maintained with increasing age. … The vaccine also showed efficacy in preventing the clinical spectrum of RSV disease regardless of race, ethnic group, sex, or World Bank geographic region and income level,” Wilson’s group reported.
Cohn and Hall commented that the mRNA-1345 results were generally similar to trial estimates for the two currently available RSV vaccines approved for use in people age 60 and up.
They noted, however, that the ConquerRSV trial may have limited generalizability, in particular for important at-risk subpopulations.
“A younger median age [of hospitalization for RSV] is observed among Black, Hispanic, and American Indian or Alaska Native persons than among White persons,” Cohn and Hall wrote. “Moreover, 75.9% of the trial participants had a score indicating ‘fit’ status on the frailty scale, and persons with immunocompromise were excluded from the trial.”
The randomized, double-blind, placebo-controlled trial enrolled 35,541 participants ages 60 and older (median age 67, 49% women). Approximately 30% of participants had stable chronic medical conditions such as advanced liver or renal disease, asthma and diabetes; about 7% had risk factors for lower respiratory tract disease, including congestive heart failure and chronic obstructive pulmonary disease (COPD).
Participants were assigned in a 1:1 ratio to receive either one dose of mRNA-1345 vaccine (50 µg) or a saline placebo injection.
Of those in the vaccine group, 58.7% experienced local adverse reactions compared with 16.2% of the placebo group.
Over a median follow-up of 112 days, the vaccine was 68.4% effective at preventing any RSV-associated acute respiratory disease (95% CI 50.9%-79.7%). Notably, the vaccine showed protection against both RSV A and RSV B subtypes, though it was less effective against RSV B.
Wilson’s group acknowledged the low case numbers in key subgroups and the exclusion of persons with certain immunocompromising conditions.
Katherine Kahn is a staff writer at MedPage Today, covering the infectious diseases beat. She has been a medical writer for over 15 years.
The study was supported by Moderna.
Wilson is employed by Moderna. Several co-authors are also employed by Moderna or reported other ties to industry.
The editorialists reported no financial disclosures.
New England Journal of Medicine
Source Reference: Wilson E, et al “Efficacy and safety of an mRNA-based RSV preF vaccine in older adults” N Eng J Med 2023; DOI: 10.1056/NEJMoa2307079.
New England Journal of Medicine
Source Reference: Cohn AC, Hall AJ “Continued progress in the development of safe and effective RSV immunizations” N Engl J Med 2023; DOI: 10.1056/NEJMe2311862.