Immunogenicity and safety of a single dose of adjuvanted RSVPreF3 vaccine in adults ≥60 years of age in China: results from a phase 3 immunobridging trial

Abstract

Introduction Respiratory syncytial virus (RSV) is an important cause of severe respiratory disease, yet no vaccine is available for older adults in China. This phase 3, randomized, partially blind immunobridging study (NCT06551181) compared a single dose of adjuvanted RSVPreF3 vaccine in ≥60-year-old Chinese adults with a non-Chinese population. Methods Chinese participants were randomized 2:1 to receive adjuvanted RSVPreF3 (RSVPreF3_China group) or placebo (Placebo_China); participants from six additional countries (RSVPreF3_Overseas) received adjuvanted RSVPreF3. The primary objective was to demonstrate non-inferiority of humoral immune responses (RSV-A/RSV-B neutralizing titers) at 1 month post-vaccination in Chinese versus non-Chinese participants. Non-inferiority was met if the upper limit of the 95% confidence interval (CI) was ≤1.5 for the geometric mean titer (GMT) ratio (RSVPreF3_Overseas over RSVPreF3_China) and ≤10% for the seroresponse rate (SRR) difference (RSVPreF3_Overseas minus RSVPreF3_China). Reactogenicity and safety were also assessed. Results Overall, 2620 participants were exposed (RSVPreF3_China: 1199; Placebo_China: 601; RSVPreF3_Overseas: 820); 2522 were included in the per protocol set at 1 month post-vaccination (RSVPreF3_China: 1175; Placebo_China: 590; RSVPreF3_Overseas: 757). Non-inferiority criteria were met for both RSV-A and RSV-B, with 95% CI upper limits of 1.20 and 1.10 for GMT ratios and 3.40% and 4.89% for SRR differences, respectively. Neutralizing titers increased at 1 month in vaccine recipients: RSV-A/RSV-B GMTs were 5523.2/8073.2 ED60 (mean geometric increase [MGI]=7.89/6.40) in the RSVPreF3_China group and 6604.5/8286.2 ED60 (MGI=8.04/6.57) in the RSVPreF3_Overseas group; GMTs remained above baseline at 6 months post-vaccination. Solicited events were more frequent in vaccine- than placebo-Chinese recipients but were mostly mild-to-moderate and transient. Pain (in 41.7% of participants in the RSVPreF3_China group versus 4.2% in the Placebo_China group) and fatigue (13.6% versus 3.2%) were the most frequently reported administration-site and systemic events, respectively. The incidence of unsolicited adverse events (reported in 11.8%–13.8% of participants across Chinese groups), serious adverse events (3.4%–6.5% across all groups), and potential immune-mediated diseases (0.2%–0.3% across all groups) was low and comparable between groups. Conclusion A single dose of adjuvanted RSVPreF3 was immunogenic and well tolerated in Chinese adults aged ≥60 years, supporting the extrapolation of global efficacy and a favorable benefit-risk profile in this population.