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Clinical Trial
. 2024 Sep 23;230(3):e647-e656.
doi: 10.1093/infdis/jiae081.

Safety and Immunogenicity of an mRNA-Based RSV Vaccine Including a 12-Month Booster in a Phase 1 Clinical Trial in Healthy Older Adults

Christine A Shaw  1 , Brandon Essink  2 , Charles Harper  2 , Runa Mithani  1 , Archana Kapoor  1 , Rakesh Dhar  1 , Lauren Wilson  1 , Ruiting Guo  1 , Catherine A Panozzo  1 , Eleanor Wilson  1 , Alana K Simorellis  1 , Caroline Reuter  1 , Sonia K Stoszek  1 , Grace L Chen  1 , Rituparna Das  1 , Jaya Goswami  1
Affiliations
Clinical Trial

Safety and Immunogenicity of an mRNA-Based RSV Vaccine Including a 12-Month Booster in a Phase 1 Clinical Trial in Healthy Older Adults

Christine A Shaw et al. J Infect Dis. .

Abstract

Background: An mRNA-based respiratory syncytial virus (RSV) vaccine, mRNA-1345, is under clinical investigation to address RSV disease burden in older adults.

Methods: Based on a randomized, observer-blind, placebo-controlled design, this phase 1 dose-ranging study evaluated the safety, reactogenicity, and immunogenicity of mRNA-1345 in adults aged 65 to 79 years. Participants were randomized to receive 1 dose of mRNA-1345 (12.5, 25, 50, 100, or 200 µg) or placebo and matched mRNA-1345 booster or placebo at 12 months.

Results: Overall, 298 participants received the first injection and 247 received the 12-month booster injection. mRNA-1345 was generally well tolerated after both injections, with the most frequently reported solicited adverse reactions being injection site pain, fatigue, headache, arthralgia, and myalgia. Reactogenicity was higher after the booster injection but with severity, time to onset, and duration similar to the first injection. A single mRNA-1345 injection boosted RSV-A and RSV-B neutralizing antibody titers and prefusion F binding antibody (preF bAb) concentrations at 1 month (geometric mean fold rises: RSV-A, 10.2-16.5; RSV-B, 5.3-12.5; preF bAb, 7.2-12.1). RSV antibody levels remained above baseline through 12 months, indicating immune persistence. A 12-month booster injection also increased RSV-A and RSV-B neutralizing antibody titers and preF bAb concentrations; titers after booster injection were numerically lower than those after the first dose, with overlapping 95% CIs.

Conclusions: mRNA-1345 was well tolerated and immunogenic following a single injection and a 12-month booster.

Clinical trials registration: NCT04528719 (ClinicalTrials.gov).

Keywords: mRNA vaccine; mRNA-1345; older adult; respiratory syncytial virus; safety and immunogenicity.

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Conflict of interest statement

Potential conflicts of interest. C. A. S., R. M., A. K., R. D., L. W., C. A. P., J. G., E. W., R. G., A. K. S., C. R., S. K. S., and G. L. C. are employees of Moderna, Inc, and may hold stock/stock options in the company. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Schematic diagram of the planned treatment groups.
Figure 2.
Figure 2.
Solicited local and systemic adverse reactions within 7 days of receiving the first and booster injections. Number of participants per group after the first injection: placebo, n = 58; mRNA-1345, 12.5 µg, n = 46; 25 µg, n = 48; 50 µg, n = 47; 100 µg, n = 48; 200 µg, n = 47. Number of participants per group after booster injection: placebo/placebo, n = 51; mRNA-1345, 12.5 µg/placebo, n = 19; 12.5 µg/12.5 µg, n = 21; 25 µg/placebo, n = 20; 25 µg/25 µg, n = 22; 50 µg/placebo, n = 21; 50 µg/50 µg, n = 18; 100 µg/placebo, n = 18; 100 µg/100 µg, n = 18; 200 µg/placebo, n = 16; 200 µg/200 µg, n = 20.
Figure 3.
Figure 3.
A, RSV-A and RSV-B neutralizing antibody GMTs and GMFR. B, preF and postF binding GMCs by time after the first injection (per-protocol set). GMC, geometric mean concentration; GMFR, geometric mean fold rise; GMT, geometric mean titer; postF, post–fusion F; preF, pre–fusion F; RSV, respiratory syncytial virus.
Figure 4.
Figure 4.
Serum RSV-A (A) and RSV-B (B) neutralizing antibody kinetics at baseline following the first injection and booster injection (per-protocol booster subset). GMT, geometric mean titer; RSV, respiratory syncytial virus.
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