Background RSV infections are frequent and can lead to respiratory complications in older adults (OA). However, there is no licensed RSV vaccine yet. Here we present immunogenicity results up to month (M) 6 after vaccination with the RSVPreF3 OA. Methods In this phase 3 multi-country ongoing study (NCT04732871), adults ≥ 60 years of age were randomized (3:1:1) to receive RSVPreF3 OA and to be followed up for 3 years. All participants received a dose of RSVPreF3 on day (D) 1. Humoral immune (HI) and cell-mediated immune (CMI) responses were measured in subsets of participants at pre-vaccination (D1), D31 and M6. HI outcomes included RSV-A and RSV-B neutralizing antibody (NAb) geometric mean titers (GMTs) and RSVPreF3-specific immunoglobulin G (IgG) antibody geometric mean concentrations (GMCs). The CMI response was assessed in terms of frequency of RSVPreF3-specific CD4+ T-cells and CD8+ T-cells expressing at least 2 activation markers including at least 1 cytokine among CD40L, 4-1BB, IL-2, TNF-α, IFN-γ, IL-13, IL-17 (polypositive T-cells). Results A total of 1653 participants received a dose of RSVPreF3 OA. Of these, 987 participants were included in the HI subset and 566 in the CMI subset at D1. The RSV-A and RSV-B GMTs and RSVPreF3-specific IgG GMCs increased between D1 and D31 followed by a decline until M6. At D31, RSV-A and RSV-B NAb GMTs were 10.5-fold and 7.8-fold higher than pre-vaccination (Figure), and RSVPreF3-specific IgG antibody GMCs was 12.2-fold higher than pre-vaccination levels. At M6, the RSV-A and RSV-B GMTs were 4.4-fold and 3.5-fold, and RSVPreF3-specific IgG antibody GMCs were 4.7-fold above pre-vaccination levels. The RSVPreF3-specific polypositive CD4+ T-cell median frequency (events/106 cells) increased from 191 (below assay quantification limit) to 1339 at D31 and declined to 666 (above assay quantification limit) by M6. No RSVPreF3-specific CD8+ T-cell response was detected after RSVPreF3 OA vaccination. Conclusion In adults ≥ 60 years of age, 1 dose of RSVPreF3 OA was shown to be immunogenic, with both high HI and specific CMI responses at D31 post-vaccination and remained 3.5–4.7 fold above pre-vaccination levels at M6. This study will continue to monitor the immunogenicity of RSVPreF3 OA up to 3 years. Funding GlaxoSmithKline Biologicals SA. Disclosures Tino F. Schwarz, Prof. Dr. MD, Biogen, Merck-Serono, Pfizer, Alexion, Bavarian Nordic, Janssen-Cilag, AstraZeneca, Biontech, MSD: Grants|GlaxoSmithKline Biologicals SA: Honoraria John E. Ervin, MD, The Alliance for Multispecialty Research – KCM: Contractual agreement for conduct of study protocol Charles Andrews, MD, GlaxoSmithKline Biologicals SA: Institutional grant|Merck and Boehringer Ingelheim: Consulting fees outside of the submitted work Delphine Collete, PhD, GlaxoSmithKline Biologicals SA: Employee|GlaxoSmithKline Biologicals SA: Stocks/Bonds Magali de Heusch, PhD, GlaxoSmithKline Biologicals SA: Employee|GlaxoSmithKline Biologicals SA: Stocks/Bonds Nathalie De Schrevel, PhD, GlaxoSmithKline Biologicals SA: Employee|GlaxoSmithKline Biologicals SA: Ownership Interest Bruno Salaun, PhD, GlaxoSmithKline Biologicals SA: Employee|GlaxoSmithKline Biologicals SA: Stocks/Bonds Marc Lievens, MSc, GlaxoSmithKline Biologicals SA: Employee|GlaxoSmithKline Biologicals SA: Stocks/Bonds Céline Maréchal, PhD, GlaxoSmithKline Biologicals SA: Employee|GlaxoSmithKline Biologicals SA: Stocks/Bonds Phoebe Nakanwagi, Master’s in Biostatistics, GlaxoSmithKline Biologicals SA: Employee Veronica Hulstrøm, PhD MD, GlaxoSmithKline Biologicals SA: Employee.

Background RSV causes respiratory infections that can lead to serious respiratory complications in older adults (OA). Presently, there is no approved vaccine to prevent RSV infections. RSVPreF3 OA is an investigational vaccine containing 120 µg RSVPreF3 and the AS01E adjuvant. Here we show safety results up to month (M) 6 post-vaccination with RSVPreF3 OA. Methods This phase 3 multi-country ongoing study (NCT04732871) enrolled adults ≥ 60 years of age over a period of 3 years. Participants were randomized (3:1:1) to receive RSVPreF3 OA with different vaccination schedules. All participants received a dose of RSVPreF3 OA on day 1. Solicited and unsolicited adverse events (AEs) were evaluated within 4 and 30 days post-vaccination. All serious AEs (SAEs) and potential immune mediated diseases (pIMDs) were collected up to M6 post-vaccination. SAEs and pIMDs related to vaccination, and fatal AEs are collected up to study end but reported here up to M6. Results Overall, 1653 participants received a dose of RSVPreF3 OA and 1618 completed the M6 follow-up. The mean age was 70.0 (±6.6) years and 54.6% were women. The most frequently reported solicited injection site reaction within 4 days post-vaccination was pain (996 participants; 60.5%, 95% confidence interval [CI]: 58.1–62.9). Twenty-two participants (1.3%, 95% CI: 0.8–2.0) reported grade 3 pain (Figure). The most reported solicited systemic reactions were myalgia (551 participants; 33.5%, 95% CI: 31.2–35.8) and fatigue (517 participants; 31.4%, 95% CI: 29.2–33.7). Twenty-five participants (1.5%) reported fever (no grade 3). Most solicited AEs were transient lasting ∼2 days and were of mild to moderate intensity. Overall, 212 (12.8%, 95% CI: 11.3–14.5) participants reported at least 1 unsolicited AE within 30 days post-vaccination. At least 1 SAE was reported by 65 participants (3.9%, 95% CI: 3.0–5.0). Seven participants (0.4%, 95% CI: 0.2–0.9) reported at least 1 pIMD. Of the SAEs and pIMDs reported, 1 event (Guillain-Barre syndrome) was considered by the investigator as related to vaccination. Fatal SAEs were reported for 6 participants; none related to vaccination. Conclusion One dose of investigational RSVPreF3 OA vaccine was well tolerated and had an acceptable safety profile in adults ≥ 60 years of age. Funding GlaxoSmithKline Biologicals SA. Disclosures Tino F. Schwarz, Prof. Dr. MD, Biogen, Merck-Serono, Pfizer, Alexion, Bavarian Nordic, Janssen-Cilag, AstraZeneca, Biontech, MSD: Grants|GlaxoSmithKline Biologicals SA: Honoraria John E. Ervin, MD, The Alliance for Multispecialty Research – KCM: Contractual agreement for conduct of study protocol Charles Andrews, MD, GlaxoSmithKline Biologicals SA: Institutional grant|Merck and Boehringer Ingelheim: Consulting fees outside of the submitted work Miguel Vicco, PhD MD, GlaxoSmithKline Biologicals SA: Employee|GlaxoSmithKline Biologicals SA: Stocks/Bonds Marc Lievens, MSc, GlaxoSmithKline Biologicals SA: Employee|GlaxoSmithKline Biologicals SA: Stocks/Bonds Céline Maréchal, PhD, GlaxoSmithKline Biologicals SA: Employee|GlaxoSmithKline Biologicals SA: Stocks/Bonds Phoebe Nakanwagi, Master’s in Biostatistics, GlaxoSmithKline Biologicals SA: Employee Veronica Hulstrøm, PhD MD, GlaxoSmithKline Biologicals SA: Employee.