Circulating spike protein found in patients with mRNA vaccine-related myocarditis

Researchers identified the presence of circulating spike protein that evaded antibody recognition in adolescents and young adults who present with myocarditis after SARS-CoV-2 messenger RNA vaccination.

In addition, antibody profiling and T-cell responses were similar among patients who developed myocarditis after messenger RNA (mRNA) vaccination compared with those who had mRNA vaccination but did not develop myocarditis, researchers reported in Circulation.

“Rarely, some individuals develop myocarditis after mRNA vaccination. The immune response driving post-vaccine myocarditis has not yet been elucidated. Understanding the immunophenotype associated with mRNA vaccine-induced myocarditis is an essential first step in preventing negative complications resulting from this novel vaccine technology,” Lael M. Yonker, MD, co-director of the Cystic Fibrosis Center, the Cystic Fibrosis Therapeutic Development Center and the Pulmonary Genetics Clinic at Massachusetts General Hospital and assistant professor of pediatrics at Harvard Medical School, and colleagues wrote. “Although epidemiological reports describe key clinical features associated with myocarditis after vaccination with BNT162b2 or mRNA-1273, here, we provide in-depth immunoprofiling of patients with post-vaccine myocarditis.”

Incidence of myocarditis or pericarditis after mRNA vaccination was reported to occur at a rate of one to two cases per 100,000 vaccinated, according to the study.

To better understand the drivers of cardiac injury after mRNA vaccination, researchers performed immunophenotyping on blood samples from 61 adolescents and young adults, of whom 16 developed myocarditis (81% male) and 45 served as controls with no myocarditis after vaccination with either the BNT162b2 (Pfizer) or mRNA-1273 (Moderna) vaccines.

Researchers conducted humoral profiling; quantified and profiled SARS-CoV-2-specific T-cell responses; and measured cytokines and SARS-CoV-2 antigens in all blood samples.

All patients who developed myocarditis after mRNA vaccination presented with chest pain, elevated cardiac troponin T (median, 260 ng/L) and elevated C-reactive protein levels (median, 29.75 mg/L).

Yonker and colleagues reported that antibody profiling and T-cell response were virtually the same between patients who developed myocarditis after mRNA vaccination compared with healthy vaccinated controls, despite a modest increase in cytokine production.

Notably, the researchers observed elevated levels of full-length spike protein (mean, 33.9 pg/mL), unbound by antibodies, in the plasma of patients who developed myocarditis after vaccination, whereas no full-length spike protein was observed in the control arm after mRNA vaccination (unpaired t test; P < .0001)

“We discovered that individuals who developed post-vaccine myocarditis uniquely exhibit elevated levels of free spike protein in circulation, unbound by anti-spike antibodies, which appear to correlate with cardiac troponin T levels and innate immune activation with cytokine release. However, adaptive immunity and T-cell responses were essentially indistinguishable from those of asymptomatic age-matched vaccinated control subjects,” the researchers wrote. “Although these findings might provide insight into the immunophenotype of vaccine-related myocarditis, they do not alter the risk-benefit ratio strongly favoring vaccination to protect against severe COVID-19-related complications.”