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

TL;DR

A clinical trial found that the mRNA-1345 RSV vaccine is safe and boosts antibody levels in solid organ transplant recipients.

Contribution

The study demonstrates the safety and immunogenicity of the mRNA-1345 vaccine in a vulnerable immunosuppressed population.

Findings

The mRNA-1345 vaccine was well-tolerated with no grade 4 adverse reactions in solid organ transplant recipients.

A single dose increased RSV-A and RSV-B neutralizing antibodies, with a second dose further boosting responses.

Antibody levels varied by transplant type and immunosuppressive drug use but improved after the second dose.

Abstract

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

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.

RSV-A and RSV-B Neutralizing Antibody GMTs In Solid Organ Transplant Recipients

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.

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.

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).

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.

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

Figures