Safety and immunogenicity of the Pfizer/BioNTech SARS-CoV-2 mRNA third booster vaccine dose against the BA.1 and BA.2 Omicron variants.

BACKGROUND: The Omicron variant of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) was identified in Japan in November 2021. This variant contains up to 36 mutations in the spike protein, the target of neutralizing antibodies, and can escape vaccine-induced immunity. A booster vaccination campaign began with healthcare workers and high-risk groups. The safety and immunogenicity of the three-dose vaccination against Omicron remain unknown. METHODS: A total of 272 healthcare workers were initially evaluated for long-term vaccine safety and immunogenicity. We further established a vaccinee panel to evaluate the safety and immunogenicity against variants of concern (VOCs), including the Omicron variants, using a live virus microneutralization assay. FINDINGS: Two-dose vaccination induced robust anti-spike antibodies and neutralization titers (NTs) against the ancestral strain WK-521, whereas NTs against VOCs were significantly lower. Within 93-247 days of the second vaccine dose, NTs against Omicron were completely abolished in up to 80% of individuals in the vaccinee panel. Booster dose induced a robust increase in anti-spike antibodies and NTs against the WK-521, Delta, and Omicron variants. There were no significant differences in the neutralization ability of sera from boosted individuals among the Omicron subvariants BA.1, BA.1.1, and BA.2. Boosting increased the breadth of humoral immunity and cross-reactivity with Omicron without changes in cytokine signatures and adverse event rate. CONCLUSIONS: The third vaccination dose is safe and increases neutralization against Omicron variants. FUNDING: This study was supported by grants from AMED (grants JP21fk0108104 and JP21mk0102146).

Transplantation of cardiac Sca-1-positive cells rather than c-Kit-positive cells preserves mitochondrial oxygen consumption of the viable myocardium following myocardial infarction in rats.

The cardiosphere-derived cell (CDC) is one of the candidate cells used for cardiac regenerative therapy. Cardiospheres are mixture of cells including c-Kit+ cells, stem cell antigen (Sca)-1+ cells, and other types of cardiac progenitor cells. In this study, we compared the effect of transplantation of isolated Sca-1+ cells and c-Kit+ cells with that of the crude CDCs (CrCDCs). Focusing on the differences in the ability for secretion of paracrine factors among 3 types of cells, we determined the effects of transplantation of these cells on cardiac intracellular signaling and mitochondrial function in rats with permanently ligated coronary arteries. We showed that the transplantation of these cells resulted in a preservation of the cardiac pump function and mitochondrial respiration at the 8th week after myocardial infarction. However, mitochondrial function in the c-Kit+ cell-transplanted group was lower than that in the other 2 groups. Furthermore, we found that activation levels of intracellular signaling proteins after cell transplantation may have been due to the ability of secretion of growth factors by these transplanted cell types. Our findings indicate the possibility that CrCDC and Sca-1+ cells rather than c-Kit+ cells may be used therapeutically to preserve cardiac function and energy metabolism after myocardial infarction.