Antibody binding and ACE2 binding inhibition is significantly reduced for both the BA1 and BA2 omicron variants.

BACKGROUND: The rapid emergence of the omicron variant and its large number of mutations led to its classification as a variant of concern (VOC) by the WHO. Subsequently, omicron evolved into distinct sublineages (e.g. BA1 and BA2), which currently represent the majority of global infections. Initial studies of the neutralizing response towards BA1 in convalescent and vaccinated individuals showed a substantial reduction. METHODS: We assessed antibody (IgG) binding, ACE2 (Angiotensin-Converting Enzyme 2) binding inhibition, and IgG binding dynamics for the omicron BA1 and BA2 variants compared to a panel of VOC/VOIs, in a large cohort (n = 352) of convalescent, vaccinated, and infected and subsequently vaccinated individuals. RESULTS: While omicron was capable efficiently binding to ACE2, antibodies elicited by infection or immunization showed reduced binding capacities and ACE2 binding inhibition compared to WT. Whereas BA1 exhibited less IgG binding compared to BA2, BA2 showed reduced inhibition of ACE2 binding. Among vaccinated samples, antibody binding to omicron only improved after administration of a third dose. CONCLUSION: omicron BA1 and BA2 can still efficiently bind to ACE2, while vaccine/infection-derived antibodies can bind omicron. The extent of the mutations within both variants prevent a strong inhibitory binding response. As a result, both omicron variants are able to evade control by pre-existing antibodies.

The Society of Thoracic Surgeons Intermacs 2022 Annual Report: Focus on 2018 Heart Transplant Allocation System.

The thirteenth annual report from The Society of Thoracic Surgeons (STS) Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs) highlights outcomes for 27,314 patients receiving continuous flow durable left ventricular assist devices (LVAD) over the last decade (2012-2021). In 2021, 2,464 primary LVADs were implanted, representing a 23.5% reduction in the annual volume compared to peak implantation in 2019 and an ongoing trend from the prior year. This decline is likely a reflection of the untoward effects of the COVID-19 pandemic and the change in the US heart transplant allocation system in 2018. The last several years have been characterized by a shift in device indication and type with 81.1% of patients now implanted as destination therapy and 92.7% receiving an LVAD with full magnetic levitation in 2021. However, despite an older, more ill population being increasingly supported pre-implant with temporary circulatory devices in the recent (2017-2021) vs prior (2012-2016) eras, the 1- and 5-year survival continues to improve at 83.0% and 51.9%, respectively. The adverse events profile has also improved, with significant reduction in stroke, gastrointestinal bleeding, and hospital readmissions. Finally, we examined the impact of the change in heart transplant allocation system in 2018 on LVAD candidacy, implant strategy, and outcomes. In the competing outcomes analysis, the proportion of transplant eligible patients receiving a transplant has declined from 56.5% to 46.0% at 3 years, while the proportion remaining alive with ongoing support has improved from 24.1% to 38.1% at 3 years, underscoring the durability of the currently available technology.

Viral T-cell epitopes - Identification, characterization and clinical application.

T-cell immunity, mediated by CD4+ and CD8+ T cells, represents a cornerstone in the control of viral infections. Virus-derived T-cell epitopes are represented by human leukocyte antigen (HLA)-presented viral peptides on the surface of virus-infected cells. They are the prerequisite for the recognition of infected cells by T cells. Knowledge of viral T-cell epitopes provides on the one hand a diagnostic tool to decipher protective T-cell immune responses in the human population and on the other hand various prophylactic and therapeutic options including vaccination approaches and the transfer of virus-specific T cells. Such approaches have already been proven to be effective against various viral infections, particularly in immunocompromised patients lacking sufficient humoral, antibody-based immune response. This review provides an overview on the state of the art as well as current studies regarding the identification and characterization of viral T-cell epitopes and approaches of clinical application. In the first chapter in silico prediction tools and direct, mass spectrometry-based identification of viral T-cell epitopes is compared. The second chapter provides an overview of commonly used assays for further characterization of T-cell responses and phenotypes. The final chapter presents an overview of clinical application of viral T-cell epitopes with a focus on human immunodeficiency virus (HIV), human cytomegalovirus (HCMV) and severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), being representatives of relevant viruses.

Durable spike-specific T-cell responses after different COVID-19 vaccination regimens are not further enhanced by booster vaccination.

Several COVID-19 vaccines are approved to prevent severe disease outcome following SARS-CoV-2 infection. Whereas the induction and functionality of anti-viral antibody response is largely studied, the induction of T cells upon vaccination with the different approved COVID-19 vaccines is less studied. Here, we reported on T-cell immunity four weeks and six months after different vaccination regimens and four weeks after an additional booster vaccination, in comparison to SARS-CoV-2 T-cell responses in convalescents and prepandemic donors using interferon-gamma ELISpot assays and flow cytometry. Increased T-cell responses and cross-recognition of B.1.1.529 Omicron variant-specific mutations were observed ex vivo in mRNA- and heterologous-vaccinated donors compared to vector-vaccinated donors. Nevertheless, potent expandability of T cells targeting the spike protein was observed for all vaccination regimens with frequency, diversity and the ability to produce several cytokines of vaccine-induced T-cell responses comparable to those in convalescent donors. T-cell responses for all vaccinated donors significantly exceeded preexisting cross-reactive T-cell responses in prepandemic donors. Booster vaccination led to a significant increase of anti-spike IgG responses, which showed a marked decline 6 month after complete vaccination. In contrast, T-cell responses remained stable over time following complete vaccination with no significant effect of booster vaccination on T-cell responses and cross-recognition of Omicron BA.1 and BA.2 mutations.This suggested that booster vaccination is of particular relevance for the amelioration of antibody response. Together, our work shows that different vaccination regimens induce broad and long-lasting spike-specific CD4+ and CD8+ T-cell immunity to SARS-CoV-2.