What information is available on the newly approved Moderna RSV vaccine (mRESVIA®) and how does it compare with other currently available RSV vaccines?
text 1 Heading link
Background
Efforts to develop a vaccine against respiratory syncytial virus (RSV) began in the 1960s.1,2 The first candidate was a formalin-inactivated vaccine, which induced severe vaccine-associated enhanced respiratory disease in RSV-naïve infants (leading to 2 deaths) during the first natural RSV infection. Following the failure of this vaccine, concerns over safety hindered alternative RSV vaccine development for many decades.2,3 However, advances in understanding the structural biology of RSV and associated technological breakthroughs have allowed for recent progress.
In May 2023, the U.S. Food and Drug Administration approved 2 vaccines, RSVPreF3 (Arexvy®, manufactured by GSK) and RSVpreF (Abrysvo®, manufactured by Pfizer) against RSV.4,5 RSVPreF3 was the first RSV vaccine to be marketed, approved for the prevention of RSV-associated lower respiratory tract disease (RSV-LRTD) in patients aged ≥60 years.4 RSVpreF was approved shortly afterward with the same indication, and in August 2023, it gained an additional, unique indication for use in pregnant individuals to protect newborns against RSV-LRTD in the first 6 months after birth.5,6 Detailed information on these 2 RSV vaccines is found in the April 2024 FAQ summary, available here.
In May 2024, the FDA approved a third RSV vaccine, mRNA-1345 (mRESVIA®, manufactured by Moderna), for the prevention of RSV-LRTD in patients aged ≥60 years.7 Moderna expects that the mRNA-1345 vaccine will be available for eligible individuals in the U.S. by the 2024–2025 RSV season.
The mRNA-1345 vaccine: characteristics and comparisons with other available RSV vaccines
Table 1 provides a comparison of the currently available RSV vaccines: RSVPreF3, RSVPreF, and mRNA-1345.8-10 As previously stated, all 3 vaccines are approved for use in patients aged ≥60 years, but there are some key differences amongst these vaccines. A notable difference regards the mechanism of protection. The mRNA-1345 vaccine is a lipid nanoparticle-encapsulated mRNA-based vaccine encoding the RSV fusion (F) glycoprotein stabilized in the prefusion (preF) conformation.10 The vaccine uses the same lipid nanoparticles as the Moderna COVID-19 vaccine.7 In contrast, RSVPreF3 and RSVPreF are non-mRNA vaccines.8,9 All 3 RSV vaccines use the stabilized preF protein as the vaccine antigen.8-10 As described in the April 2024 FAQ summary (available here), the F glycoprotein is a protein expressed on the RSV surface that mediates the fusion of the viral and host cell membranes.1 The preF conformation of the F protein is a major target of potent neutralizing antibodies and is highly conserved across both RSV subtypes (RSV-A and RSV-B).7
The RSVPreF3 and RSVPreF vaccines are available in vials containing lyophilized powder that must be reconstituted with the accompanying diluents prior to administration.8,9 The availability of the mRNA-1345 vaccine in single-dose prefilled syringes offers a potential convenience edge over the other 2 vaccines.10 The mRNA-1345 vaccine is dosed similarly to RSVPreF3 and RSVPreF, although there are differences in the antigen component delivered.8-10 For RSVPreF3 and RSVPreF, a single 0.5 mL dose contains 120 mcg of the preF antigen component. For mRNA-1345, a single 0.5 mL dose contains 50 mcg of nucleoside modified mRNA encoding the RSV F glycoprotein stabilized in the preF conformation.
With the RSVPreF3 and RSVpreF vaccines, serious cases of atrial fibrillation, as well as rare episodes of neuroinflammatory events such as Guillain-Barré syndrome and acute disseminated encephalomyelitis, have been reported; a causal relationship between these events and these RSV vaccines has not been established.8,9 Similar serious adverse events were not observed with mRNA-1345 vaccine; however, 1 case of facial paralysis (assessed as vaccine-related) has been reported.10
table 1 Heading link
| Table 1. Comparisons of the currently available RSV vaccines.8-10 | |||
|---|---|---|---|
| RSVPreF3 (Arexvy®; GSK) | RSVPreF (Abrysvo®; Pfizer) | mRNA-1345 (mRESVIA®; Moderna) |
|
| FDA approval date | May 3, 2023 | May 31, 2023 | May 31, 2024 |
| Approved indication(s) | Persons aged ≥60 years for the prevention of RSV-LRTD | Persons aged ≥60 years for the prevention of RSV-LRTD Pregnant persons at 32 to 36 weeks of gestation for the prevention of RSV-LRTD in infants through 6 months of age | Persons aged ≥60 years for the prevention of RSV-LRTD |
| Vaccine components | Single-dose vial of lyophilized powder (antigen component) Single-dose vial of liquid adjuvant suspension (diluent component) | Kits: Vial of lyophilized powder (antigen component) Syringe with sterile water (diluent component) Vial adapter Cartons: Vials of lyophilized powder (antigen component) Vials with sterile water (diluent component) | Single-dose prefilled plastic syringe |
| Preparation for administrationa | Reconstitute the lyophilized powder (antigen component) with the accompanying adjuvant suspension (diluent component) | For both presentations (kits and cartons): Reconstitute the lyophilized powder (antigen component) with the accompanying sterile water (diluent component) | Thaw the frozen suspension in the pre-filled syringe |
| Dosage | 0.5 mL once | ||
| Administration route | Intramuscular | ||
| Contraindication | History of severe allergic reaction (e.g., anaphylaxis) to any vaccine component | ||
| Warnings | Allergic vaccine reactions Syncope Potential diminished immune response to the vaccine in immunocompromised persons | Allergic vaccine reactions Syncope Potential diminished immune response to the vaccine in immunocompromised persons Potential risk of preterm birth | Allergic vaccine reactions Syncope Potential diminished immune response to the vaccine in immunocompromised persons |
| Common adverse effects (incidence ≥10%) | Injection site pain, fatigue, myalgia, headache, arthralgia | In persons aged ≥60 years: Fatigue, headache, injection site pain, myalgia In pregnant persons: Injection site pain, headache, myalgia, nausea | Injection site pain, fatigue, headache, myalgia, arthralgia, axillary swelling/tenderness, chills |
| Storageb | Before reconstitution: In the refrigerator (36 ºF to 47°F) in original carton; protect from light After reconstitution: Use immediately; otherwise, store in the refrigerator (36 ºF to 47°F) or at room temperature (59ºF to 86ºF); use within 4 hours; protect from light | Before reconstitution: In the refrigerator (36 ºF to 47°F) in original carton After reconstitution: Use immediately; otherwise, store at room temperature (59ºF to 86ºF); use within 4 hours | Minimize exposure to room light; avoid exposure to direct sunlight and ultraviolet light Before thawing: In the freezer between -40°F to 5°F After thawing: May be stored under refrigeration (36°F to 46°F) for ≤30 days prior to use May be stored between 46°F to 77°F for a total of 24 hours after removal from the refrigerator; discard if not used within this time |
| aFor RSVPreF3 and RSVPreF, refer to the prescribing information for detailed steps for reconstitution. For mRNA-1345, refer to the prescribing information for thawing conditions and times. bRefer to the prescribing information for additional storage information. Abbreviations: FDA, Food and Drug Administration; RSV, respiratory syncytial virus; RSV-LRTD, respiratory syncytial virus-associated lower respiratory tract disease. |
|||
text 2 Heading link
Clinical data for the mRNA-1345 vaccine
The approval of mRNA-1345 was based on results from an ongoing, phase 3, randomized, double-blind, placebo-controlled, multicenter trial (ConquerRSV).11 In this trial, 35,541 adults aged ≥60 years (mean age at baseline, 68.1 years) were randomized 1:1 to receive a single dose of mRNA-1345 50 μg or placebo intramuscularly. Approximately 29.3% of patients had ≥1 coexisting condition at enrollment, with 1.1% and 5.5% reporting a history of congestive heart failure and chronic obstructive pulmonary disease, respectively; additionally, 21.9% of patients were assessed as vulnerable or frail. Two primary efficacy endpoints were assessed: a) the prevention of RSV-LRTD with ≥2 signs or symptoms and b) the prevention of RSV-LRTD with ≥3 signs or symptoms. A key secondary endpoint was prevention of RSV-associated acute respiratory disease.
As of the data-cutoff date (November 30, 2022), the median follow-up was 112 days, with 20.4% of patients having been followed for ≥6 months.11 Nine cases of RSV-LRTD with ≥2 signs/ symptoms were reported in the mRNA-1345 group compared to 55 cases in the placebo group; vaccine efficacy was 83.7% (95.88% confidence interval [CI], 66.0 to 92.2; p<0.001). Three cases RSV-LRTD with ≥3 signs/symptoms were reported in the mRNA-1345 group compared to 17 cases in the placebo group; vaccine efficacy was 82.4% (96.36% CI, 34.8 to 95.3; p=0.008). For RSV-associated acute respiratory disease, 26 and 82 cases occurred in the mRNA-1345 and placebo groups, respectively; vaccine efficacy was 68.4% (95% CI, 50.9 to 79.7). Protection was observed against both the RSV-A and RSV-B subtypes for these endpoints. Patients who received mRNA-1345 had a higher incidence than those who received placebo of solicited local adverse reactions (58.7% versus 16.2%) and of systemic adverse reactions (47.7% versus 32.9%); most reactions were transient, and mild to moderate in severity. No major safety concerns were identified. The trial is following patients for 24 months after injection; final findings have not yet been published.12
Guideline recommendations
Recommendations for RSV vaccination in older adults were formalized by the Advisory Committee on Immunization Practices (ACIP) in June 2023.13 The ACIP and Centers for Disease Control and Prevention (CDC) recommend that adults aged ≥60 years may receive a single dose of RSV vaccine (RSVPreF3 or RSVpreF) to protect against severe RSV, using shared clinical decision-making.13,14 Refer to the April 2024 FAQ summary (available here) for additional details. Current vaccination guidelines predate mRNA-1345 approval; specific recommendations on this vaccine have not been made by the ACIP or CDC.
Conclusion
After RSVPreF3 and RSVpreF, mRNA-1345 is the third RSV vaccine to be approved for individuals aged ≥60 years.5-7 The approval was based on the ConquerRSV trial which showed a lower incidence of RSV-LRTD and RSV-associated acute respiratory disease with mRNA-1345 compared to placebo with 3.7 months of median patient follow-up, without major safety concerns; further follow-up is ongoing to determine the duration of protection afforded by the vaccine.10,11 Compared to RSVPreF3 and RSVpreF, the mRNA-1345 vaccine is distinguished by its unique mechanism of protection and availability in single-dose prefilled syringes.10 The CDC and ACIP currently recommend that adults aged ≥60 years may receive a single dose of RSV vaccine using shared clinical decision-making; the mRNA-1345 vaccine has not yet been incorporated into the recommendations.13,14 The CDC/ACIP review of the mRNA-1345 vaccine is pending prior to its commercial launch, which is expected by the 2024–2025 RSV season.7 As RSV vaccination options expand and newer clinical data emerge, clinicians should stay up-to-date with current information and recommendations on RSV vaccination.
References
- Topalidou X, Kalergis AM, Papazisis G. Respiratory syncytial virus vaccines: a review of the candidates and the approved vaccines. Pathogens. 2023;12(10). doi:10.3390/pathogens12101259
- Respiratory syncytial virus (RSV) disease. World Health Organization. Accessed May 5, 2024. https://www.who.int/teams/health-product-policy-and-standards/standards-and-specifications/vaccine-standardization/respiratory-syncytial-virus-disease
- Venkatesan P. First RSV vaccine approvals. Lancet Microbe. 2023;4(8):e577. doi:10.1016/S2666-5247(23)00195-7
- FDA approves first respiratory syncytial virus (RSV) vaccine. U.S. Food and Drug Administration. Published May 3, 2023. Updated May 4, 2023. Accessed June 11, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-respiratory-syncytial-virus-rsv-vaccine
- U.S. FDA approves ABRYSVO™, Pfizer’s vaccine for the prevention of respiratory syncytial virus (RSV) in older adults. Pfizer. Published May 31, 2023. Accessed June 11, 2024. https://www.pfizer.com/news/press-release/press-release-detail/us-fda-approves-abrysvotm-pfizers-vaccine-prevention
- FDA approves first vaccine for pregnant individuals to prevent RSV in infants. U.S. Food and Drug Administration. Published August 21, 2023. Updated August 22, 2023. Accessed June 11, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-vaccine-pregnant-individuals-prevent-rsv-infants
- Moderna receives U.S. FDA approval for RSV vaccine mRESVIA(R). Moderna. Published May 31, 2024. Updated August 22, 2023. Accessed June 11, 2024. https://investors.modernatx.com/news/news-details/2024/Moderna-Receives-U.S.-FDA-Approval-for-RSV-Vaccine-mRESVIAR/default.aspx
- Arexvy. Package insert. GlaxoSmithKline Biologicals; 2023.
- Abrysvo. Package insert. Pfizer; 2024.
- mRESVIA. Package insert. Moderna; 2024.
- Wilson E, Goswami J, Baqui AH, et al. Efficacy and safety of an mRNA-based RSV PreF vaccine in older adults. N Engl J Med. 2023;389(24):2233-2244. doi:10.1056/NEJMoa2307079
- A study to evaluate the safety and efficacy of mRNA-1345 vaccine targeting respiratory syncytial virus (RSV) in adults ≥60 years of age. ClinicalTrials.gov identifier: NCT05127434. Updated February 9, 2024. Accessed June 11, 2024. https://clinicaltrials.gov/study/NCT05127434?cond=NCT05127434&rank=1
- Melgar M, Britton A, Roper LE, et al. Use of respiratory syncytial virus vaccines in older adults: recommendations of the Advisory Committee on Immunization Practices – United States, 2023. MMWR Morb Mortal Wkly Rep. 2023;72(29):793-801. doi:10.15585/mmwr.mm7229a4
- Healthcare providers: RSV vaccination for adults 60 years of age and over. Centers for Disease Control and Prevention. Updated March 1, 2024. Accessed June 11, 2024. https://www.cdc.gov/vaccines/vpd/rsv/hcp/older-adults.html
Prepared by:
Honey Joseph, PharmD, BCPS
Clinical Assistant Professor, Drug Information Specialist
University of Illinois at Chicago College of Pharmacy
July 2024
The information presented is current as of June 11, 2024. This information is intended as an educational piece and should not be used as the sole source for clinical decision-making.