BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans.

BNT162b2, a nucleoside-modified mRNA formulated in lipid nanoparticles that encodes the SARS-CoV-2 spike glycoprotein (S) stabilized in its prefusion conformation, has demonstrated 95% efficacy in preventing COVID-191. Here we extend a previous phase-I/II trial report2 by presenting data on the immune response induced by BNT162b2 prime-boost vaccination from an additional phase-I/II trial in healthy adults (18-55 years old). BNT162b2 elicited strong antibody responses: at one week after the boost, SARS-CoV-2 serum geometric mean 50% neutralizing titres were up to 3.3-fold above those observed in samples from individuals who had recovered from COVID-19. Sera elicited by BNT162b2 neutralized 22 pseudoviruses bearing the S of different SARS-CoV-2 variants. Most participants had a strong response of IFNγ+ or IL-2+ CD8+ and CD4+ T helper type 1 cells, which was detectable throughout the full observation period of nine weeks following the boost. Using peptide-MHC multimer technology, we identified several BNT162b2-induced epitopes that were presented by frequent MHC alleles and conserved in mutant strains. One week after the boost, epitope-specific CD8+ T cells of the early-differentiated effector-memory phenotype comprised 0.02-2.92% of total circulating CD8+ T cells and were detectable (0.01-0.28%) eight weeks later. In summary, BNT162b2 elicits an adaptive humoral and poly-specific cellular immune response against epitopes that are conserved in a broad range of variants, at well-tolerated doses.

Wall motion changes in myocardial infarction in relation to the time elapsed from symptoms until revascularization.

OBJECTIVE: Wall motion abnormalities during acute ST-segment elevation myocardial infarction (STEMI) and the improvement after recanalization depend on the conditions of the coronary occlusion. METHODS: Fifty-seven patients with first-ever STEMI due to one-artery occlusion, treated with primary PCI, were evaluated. Area at risk and left ventricular wall motion abnormalities were localized with coronary angiography and echocardiography and then compared in relation to the time elapsed from the onset of symptoms at the time of infarction and at 3 months. Left ventricular diameters and ejection fractions were evaluated in relation to the ischemic time. RESULTS: Three hundred forty-one affected left ventricular segments were detected with angiography, while echocardiography showed 206 segments with motion abnormality. No correlation was found between the regional wall motion index in the area at risk and the time elapsed from the beginning of symptoms. However, the improvement in wall motion abnormalities at the follow-up was dependent on the ischemic time (r=-0.29, p<0.03). The early subgroup showed significant improvement in left ventricular ejection fraction at follow-up (p=0.03), whereas in the late subgroup, a significant increase in left ventricle diameters was observed. CONCLUSION: Our results first demonstrate in humans that in the early hours from the occlusion of the coronary artery, the extent and severity of the wall motion abnormalities inside the area at risk show large variability without relation to the elapsed time since the onset of symptoms. On the other hand, the results of follow-up echocardiography proved that the wall motion improvement was highly dependent on the ischemic time.