Safety, Tolerability, and Immunogenicity of the mRNA-1345 RSV Vaccine in Solid Organ Transplant Recipients Aged ≥18 Years

Abstract Background Solid organ transplant recipients (SOTRs) are at increased risk for severe respiratory syncytial virus (RSV) disease due to chronic immunosuppression. Interim safety and immunogenicity are presented from a phase 3 trial evaluating 2 mRNA-1345 doses in SOTRs ≥18 years.Figure 1.Solicited Local and Systemic Reactions within 7 Days After the First and Second Injections (Solicited Safety Set)Dose 1, N = 150; Dose 2, N = 146.Percentages are based on the number of exposed participants who submitted any data for the event.No grade 4 solicited adverse reactions were reported besides a single grade 4 systemic reaction of arthralgia reported for 1 participant (0.7%) after Dose 2.Figure 2.RSV-A and RSV-B Neutralizing Antibody GMTs In Solid Organ Transplant Recipients Methods An ongoing, open-label, phase 3 trial (NCT06067230) evaluated 2 mRNA-1345 50-µg doses, 56 days apart, in adults ≥18 years with liver, kidney, or lung transplant ≥180 days prior to the study. Primary objectives included safety, tolerability, and immunogenicity assessed by RSV-A and -B neutralizing antibodies (nAbs). Primary objective included measurement of geometric mean titers (GMTs) on Day 85; secondary objective included measurement of GMTs on Day 29.Figure 3.RSV-A and RSV-B Neutralizing Antibody GMTs Based on Time since Transplant (blue curves) and Use of Mycophenolate Mofetil (orange/yellow curves)MMF, mycophenolate mofetil; SOTR, solid organ transplant recipient. Results Of 150 SOTR (50 kidney, 52 liver, and 48 lung), 146 received both doses. Median follow-up from Dose 1 was 223 days (range 8-335). Median age was 57 years (range 24–80), 37.3% were female, and 26.7% received SOT 2 years prior. Most participants (80.6%) were taking concomitant tacrolimus ± mycophenolate ± steroids. Solicited adverse reactions (SARs) within 7 days were similar after both doses (local: 74.0%, 77.4%; systemic: 64.0%, 64.4%; Fig. 1). No grade 4 local SARs, adverse events (AEs) leading to study/vaccine discontinuation, deaths, or AEs of special interest were reported. One month after Dose 1, RSV-A nAbs rose 4.9-fold from baseline; 1 month after Dose 2, nAbs rose 7.1-fold from baseline (Fig. 2). RSV-B nAb response had a 3.4-fold increase from baseline after Dose 1, and a 5.2-fold increase after Dose 2. Titers achieved varied by SOT type. Liver SOTR titers after Dose 1 were comparable to those observed in non-immunocompromised adults in the pivotal efficacy trial . GMTs were lower in kidney and lung SOTRs, SOTRs 2 years post-transplant, and those on mycophenolate mofetil (MMF), but increased after Dose 2 (Fig. 3). Conclusion Two doses of mRNA-1345 50-µg administered 56 days apart in SOTRs were well-tolerated, with no safety concerns. A single dose was immunogenic across all SOTR groups, and a second dose boosted responses, especially in kidney SOTRs, lung SOTRs, those 2 years post-transplant, or on MMF; therefore, mRNA-1345 is likely to be effective in this vulnerable population. Disclosures Dima Kabbani, MD, MSc, AvirPharma Inc.: Grant/Research Support|AvirPharma Inc.: Honoraria for education lectures|F2G: Grant/Research Support|Moderna: Grant/Research Support|Pulmocide Ltd.: Grant/Research Support|Takeda Canada: Consultant fee Deepali Kumar, MD, MSc, FRCPC, Eurofins Viracor: Honoraria|GSK: Advisor/Consultant|GSK: Grant/Research Support|Merck and Company, Inc.: Advisor/Consultant|Moderna, Inc.: Grant/Research Support|Paladin Labs: Honoraria|Takeda Canada: Advisor/Consultant|Takeda Canada: Grant/Research Support