P-1447. T-Cell Responses Following Two Doses of mRNA-1345 in Adult Solid Organ Transplant Recipients

TL;DR

This study shows that an mRNA vaccine can generate lasting T-cell responses in organ transplant recipients, who are typically immunosuppressed.

Contribution

The study demonstrates that mRNA-1345 induces durable Th1-biased CD4+ T-cell responses in a severely immunocompromised population.

Findings

RSV-F–specific CD4+ Th1 responses increased after the first vaccine dose and further increased after the second dose.

CD8+ Th1 responses were observed by the second dose, and T-cell responses persisted for six months.

Th2 responses were minimal and transient, with no evidence of polyfunctionality.

Abstract

Solid organ transplant recipients (SOTRs) are at elevated risk for severe respiratory syncytial virus (RSV) disease due to chronic immunosuppression. Cell-mediated immune responses are likely an important component of long-lasting protection against RSV. This substudy evaluates RSV-F–specific T-cell responses following 1 and 2 doses of mRNA-1345 50 µg in adult SOTRs.Figure 1.RSV PreF-Specific CD4+ Th1 Responses (IFNγ+) Through 6 Months After Vaccination With mRNA-1345 (50 µg) on Day 1 and Day 57 in Adult SOTRs

RSV PreF-Specific CD4+ Th1 Responses (IFNγ+) Through 6 Months After Vaccination With mRNA-1345 (50 µg) on Day 1 and Day 57 in Adult SOTRs

Adults ≥18 years with a kidney, liver, or lung transplant received 2 doses of mRNA-1345 50 µg administered 57 days apart in an ongoing, phase 3 trial (NCT06067230). Peripheral blood mononuclear cells were optionally collected from a subset of participants at baseline (Day 1, pre-dose 1), Day 15, Day 57 (pre-dose 2), Day 71, and Day 181. RSV-F (prefusion conformation) T-cell responses were assessed; CD4+ and CD8+ cells were evaluated with intracellular cytokine staining for Th1 (IFN, TNF, IL2) or Th2 (IL4, IL5, IL13) responses, in addition to other functional markers (ie, CD40L, a marker of B cell co-stimulation).

Among 42 SOTRs (24 kidney, 8 lung, 8 liver, and 2 combined liver-kidney), RSV-F–specific CD4+ Th1 responses increased following the first mRNA-1345 dose, with an additional increase observed after Dose 2. Responses remained elevated through Day 181 (Figure). Polyfunctional CD4+ Th1 cells (expressing ≥2 or ≥3 cytokines) followed a similar trajectory. CD8+ Th1 responses were observed by Day 57. CD4+ Th2 responses showed minimal increases after Dose 1 and Dose 2, with no evidence of polyfunctionality, and were trending downward by Day 181. These trends were observed consistently across transplant types.

mRNA-1345 50 µg elicited Th1-biased CD4+ T-cell responses with minimal and transient Th2 activation in adult SOTRs. CD8+ T-cell responses were also observed. T-cell responses persisted for 6 months post-vaccination. Findings demonstrate the ability of mRNA-1345 to induce cellular immunity in severely immunocompromised population, with durable responses which may be important for prevention of severe disease over time.

Erick F. Mayer, MD, Moderna, Inc.: Employee of Moderna, Inc.|Moderna, Inc.: Stocks/Bonds (Public Company) Ann R. Falsey, MD, ADMA Biologics: Advisor/Consultant|ADMA Biologics: Honoraria|AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|AstraZeneca: Honoraria|CynaVac: Grant/Research Support|GSK: Advisor/Consultant|GSK: Honoraria|Merck: Advisor/Consultant|Merck: Honoraria|Moderna, Inc.: Advisor/Consultant|Moderna, Inc.: Grant/Research Support|Moderna, Inc.: Honoraria|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant|Sanofi Pasteur: Honoraria Christina Grassi, MD, Moderna, Inc.: Employee of Moderna, Inc.|Moderna, Inc.: Stocks/Bonds (Public Company) Avi Collins, BScN, Moderna, Inc.: Former Moderna, Inc. Employee|Moderna, Inc.: Stocks/Bonds (Public Company) Md Hasan, PhD, Moderna, Inc.: Employee|Moderna, Inc.: Stocks/Bonds (Public Company) Hsiaohsuan Kuo, PhD, Moderna, Inc.: Employee|Moderna, Inc.: Stocks/Bonds (Public Company) Shannon McGrath, MS, Moderna, Inc.: Employee|Moderna, Inc.: Stocks/Bonds (Public Company) Archana Kapoor, PhD, Moderna, Inc.: Employee of Moderna, Inc.|Moderna, Inc.: Stocks/Bonds (Public Company) Xiaolin Chang, PhD, Moderna, Inc.: Moderna, Inc. employee|Moderna, Inc.: Stocks/Bonds (Public Company) Xing Chen, Sc.D., Moderna, Inc.: Moderna, Inc. employee|Moderna, Inc.: Stocks/Bonds (Public Company) Lan Lan, PhD, Moderna, Inc.: Employee of Moderna, Inc.|Moderna, Inc.: Stocks/Bonds (Public Company) Sonia K. Stoszek, PhD, Moderna, Inc.: Employee of Moderna, Inc.|Moderna, Inc.: Stocks/Bonds (Public Company) Eleanor Wilson, MD, MHS, Moderna, Inc.: Employee of Moderna, Inc.|Moderna, Inc.: Stocks/Bonds (Public Company) Jaya Gowami, MD, Moderna, Inc.: Employee of Moderna, Inc.|Moderna, Inc.: Stocks/Bonds (Public Company) Rituparna Das, M.D., Moderna, Inc.: Employee|Moderna, Inc.: Stocks/Bonds (Public Company) Frances Priddy, MD, MPH, Moderna, Inc.: Employee of Moderna, Inc.|Moderna, Inc.: Stocks/Bonds (Private Company)

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