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

Overview

Journal J Infect Dis

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2024 Feb 22

PMID 38385566

Authors

Christine A Shaw

Brandon Essink

Charles Harper

Runa Mithani

Archana Kapoor

Rakesh Dhar

Lauren Wilson

Ruiting Guo

Catherine A Panozzo

Eleanor Wilson

Alana K Simorellis

Caroline Reuter

Sonia K Stoszek

Grace L Chen

Rituparna Das

Jaya Goswami

Affiliations

Soon will be listed here.

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).

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