Comparative analysis of COVID-19 vaccine responses and third booster dose-induced neutralizing antibodies against Delta and Omicron variants

Vaccination shows efficacy in protecting from COVID-19, but regime and dosing optimization is still ongoing. Here the authors show that BNT162b2, mRNA-1273, or their combination with ChAdOx1 induces similar antibody responses, and those receiving three doses of BNT162b2 induce neutralizing antibodies against the Omicron variant.Two COVID-19 mRNA (of BNT162b2, mRNA-1273) and two adenovirus vector vaccines (ChAdOx1 and Janssen) are licensed in Europe, but optimization of regime and dosing is still ongoing. Here we show in health care workers (n = 328) that two doses of BNT162b2, mRNA-1273, or a combination of ChAdOx1 adenovirus vector and mRNA vaccines administrated with a long 12-week dose interval induce equally high levels of anti-SARS-CoV-2 spike antibodies and neutralizing antibodies against D614 and Delta variant. By contrast, two doses of BNT162b2 with a short 3-week interval induce 2-3-fold lower titers of neutralizing antibodies than those from the 12-week interval, yet a third BNT162b2 or mRNA-1273 booster dose increases the antibody levels 4-fold compared to the levels after the second dose, as well as induces neutralizing antibody against Omicron BA.1 variant. Our data thus indicates that a third COVID-19 mRNA vaccine may induce cross-protective neutralizing antibodies against multiple variants.</p

1α,25(OH)2-3-Epi-Vitamin D3, a Natural Physiological Metabolite of Vitamin D3: Its Synthesis, Biological Activity and Crystal Structure with Its Receptor

Background: The 1 alpha,25-dihydroxy-3-epi-vitamin-D(3) (1 alpha,25(OH)(2)-3-epi-D(3)), a natural metabolite of the seco-steroid vitamin D(3), exerts its biological activity through binding to its cognate vitamin D nuclear receptor (VDR), a ligand dependent transcription regulator. In vivo action of 1 alpha,25(OH)(2)-3-epi-D(3) is tissue-specific and exhibits lowest calcemic effect compared to that induced by 1 alpha,25(OH)(2)D(3). To further unveil the structural mechanism and structure-activity relationships of 1 alpha,25(OH)(2)-3-epi-D3 and its receptor complex, we characterized some of its in vitro biological properties and solved its crystal structure complexed with human VDR ligand-binding domain (LBD). Methodology/Principal Findings: In the present study, we report the more effective synthesis with fewer steps that provides higher yield of the 3-epimer of the 1 alpha,25(OH)(2)D(3). We solved the crystal structure of its complex with the human VDR-LBD and found that this natural metabolite displays specific adaptation of the ligand-binding pocket, as the 3-epimer maintains the number of hydrogen bonds by an alternative water-mediated interaction to compensate the abolished interaction with Ser278. In addition, the biological activity of the 1 alpha,25(OH)(2)-3-epi-D(3) in primary human keratinocytes and biochemical properties are comparable to 1 alpha,25(OH)(2)D(3). Conclusions/Significance: The physiological role of this pathway as the specific biological action of the 3-epimer remains unclear. However, its high metabolic stability together with its significant biologic activity makes this natural metabolite an interesting ligand for clinical applications. Our new findings contribute to a better understanding at molecular level how natural metabolites of 1 alpha,25(OH)(2)D(3) lead to significant activity in biological systems and we conclude that the C3-epimerization pathway produces an active metabolite with similar biochemical and biological properties to those of the 1 alpha,25(OH)(2)D(3)

Adapting to a warmer ocean – seasonal shift of baleen whale movements over three decades

Date of Acceptance: 11/02/2015Global warming poses particular challenges to migratory species, which face changes to the multiple environments occupied during migration. For many species, the timing of migration between summer and winter grounds and also within-season movements are crucial to maximise exploitation of temporarily abundant prey resources in feeding areas, themselves adapting to the warming planet. We investigated the temporal variation in the occurrence of fin (Balaenoptera physalus) and humpback whales (Megaptera novaeangliae) in a North Atlantic summer feeding ground, the Gulf of St. Lawrence (Canada), from 1984 to 2010 using a long-term study of individually identifiable animals. These two sympatric species both shifted their date of arrival at a previously undocumented rate of more than 1day per year earlier over the study period thus maintaining the approximate 2-week difference in arrival of the two species and enabling the maintenance of temporal niche separation. However, the departure date of both species also shifted earlier but at different rates resulting in increasing temporal overlap over the study period indicating that this separation may be starting to erode. Our analysis revealed that the trend in arrival was strongly related to earlier ice break-up and rising sea surface temperature, likely triggering earlier primary production. The observed changes in phenology in response to ocean warming are a remarkable example of phenotypic plasticity and may partly explain how baleen whales were able to survive a number of changes in climate over the last several million years. However, it is questionable whether the observed rate of change in timing can be maintained. Substantial modification to the distribution or annual life cycle of these species might be required to keep up with the ongoing warming of the oceans.Publisher PDFPeer reviewe