A Phase I/II Randomized Trial of Higher Dose Mrna-1273 Boosters in Lung Transplant Recipients

Higher-dose mRNA booster vaccines have not been well studied for transplant recipients. This study evaluated the safety, reactogenicity and immunogenicity of higher dose mRNA-1273 booster vaccines among lung transplant recipients (LTRs). This phase 1/2 open-label randomized clinical trial of higher-dose mRNA-1273 booster vaccination enrolled nineteen adult LTRs into the 50 ug (n=8) vs. 100 ug (n=11) groups before enrollment was terminated due to the availability of the bivalent mRNA-1273.222 vaccine. Local and systemic reactogenicity was predominantly mild or moderate in severity for both dose groups, mostly limited to pain at the injection site, fatigue and headache. Humoral and cellular immune responses were weak. Overall, 75% and 64% of the 50 ug and 100 ug groups had detectable neutralizing antibodies on Day 30 (vs. 63% and 55% on Day 1), respectively. On Day 30, 50% and 55% had detectable spike-specific CD4+ IFN responses (vs. 29% and 36% on Day 1), and 50% and 36% had detectable CD8+ IFN responses (vs. 29% and 45% on Day 1) for the two groups, respectively. LTRs have reactogenicity and immune responses that are attenuated compared with the non-immunocompromised population. Administration of higher doses in solid organ transplant patients may be warranted. Clinical trial NCT05280158.