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Introduction: The evolution of novel SARS-CoV-2 variants significantly affects vaccine effectiveness. While these effects can only be studied retrospectively, neutralizing antibody titers are most used as correlates of protection. However, studies assessing neutralizing antibody titers often show heterogeneous data. Methods: To address this, we investigated assay variance and identified virus infection time and dose as factors affecting assay robustness. We next measured neutralization against Omicron sub-variants in cohorts with hybrid or vaccine induced immunity, identifying a gradient of immune escape potential. To evaluate the effect of individual mutations on this immune escape potential of Omicron variants, we systematically assessed the effect of each individual mutation specific to Omicron BA.1, BA.2, BA.2.12.1, and BA.4/5. Results: We cloned a library of pseudo-viruses expressing spikes with single point mutations, and subjected it to pooled sera from vaccinated hosts, thereby identifying multiple mutations that independently affect neutralization potency. Discussion: These data might help to predict antigenic features of novel viral variants carrying these mutations and support the development of broad monoclonal antibodies. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic remains a global health threat and novel antiviral strategies are urgently needed. SARS-CoV-2 employs the cellular serine protease TMPRSS2 for entry into lung cells, and TMPRSS2 inhibitors are being developed for COVID-19 therapy. However, the SARS-CoV-2 Omicron variant, which currently dominates the pandemic, prefers the endo/lysosomal cysteine protease cathepsin L over TMPRSS2 for cell entry, raising doubts as to whether TMPRSS2 inhibitors would be suitable for the treatment of patients infected with the Omicron variant. Nevertheless, the contribution of TMPRSS2 to the spread of SARS-CoV-2 in the infected host is largely unclear. In this study, we show that the loss of TMPRSS2 strongly reduced the replication of the Beta variant in the nose, trachea and lung of C57BL/6 mice, and protected the animals from weight loss and disease. The infection of mice with the Omicron variant did not cause disease, as expected, but again, TMPRSS2 was essential for efficient viral spread in the upper and lower respiratory tract. These results identify the key role of TMPRSS2 in SARS-CoV-2 Beta and Omicron infection, and highlight TMPRSS2 as an attractive target for antiviral intervention. [ABSTRACT FROM AUTHOR]

With the emergence of novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Variants of Concern (VOCs), vaccination studies that elucidate the efficiency and effectiveness of a vaccination campaign are critical to assess the durability and the protective immunity provided by vaccines. SARS-CoV-2 vaccines have been found to induce robust humoral and cell-mediated immunity in individuals vaccinated with homologous vaccination regimens. Recent studies also suggest improved immune response against SARS-CoV-2 when heterologous vaccination strategies are employed. Yet, few data exist on the extent to which heterologous prime-boost-boost vaccinations with two different vaccine platforms have an impact on the T cell-mediated immune responses with a special emphasis on the currently dominantly circulating Omicron strain. In this study, we collected serum and peripheral blood mononuclear cells (PBMCs) from 57 study participants of median 35-year old's working in the health care field, who have received different vaccination regimens. Neutralization assays revealed robust but decreased neutralization of Omicron VOC, including BA.1 and BA.4/5, compared to WT SARS-CoV-2 in all vaccine groups and increased WT SARSCoV-2 binding and neutralizing antibodies titers in homologous mRNA primeboost-boost study participants. By investigating cytokine production, we found that homologous and heterologous prime-boost-boost-vaccination induces a robust cytokine response of CD4+ and CD8+ T cells. Collectively, our results indicate robust humoral and T cell mediated immunity against Omicron in homologous and heterologous prime-boost-boost vaccinated study participants, which might serve as a guide for policy decisions. [ABSTRACT FROM AUTHOR]

Nevertheless, although Nafamostat-mediated inhibition of -1PRF did not translate into reduced SARS-CoV-2 replication in our study, interference with SARS-CoV-2 -1PRF by more potent compounds could still represent a promising antiviral strategy. Nafamostat-Mediated Inhibition of SARS-CoV-2 Ribosomal Frameshifting Is Insufficient to Impair Viral Replication in Vero Cells. Importantly, the same Nafamostat concentration that inhibited -1PRF in Vero 76 cells did not block SARS-CoV-2 infection of these cells, although it reduced infection of a control cell line, Calu-3, by more than a thousand-fold. Vero 76 and Calu-3 cells were incubated with the indicated 10-fold serial dilutions of Nafamostat for 1 h prior to infection with SARS-CoV-2, Pango lineage B.1.513, at a multiplicity of infection of 0.01 for 1 h. [Extracted from the article]

Effective vaccines and monoclonal antibodies have been developed against coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). However, the appearance of virus variants with higher transmissibility and pathogenicity is a major concern because of their potential to escape vaccines and clinically approved SARS‐CoV‐2‐ antibodies. Here, we use flow cytometry‐based binding and pseudotyped SARS‐CoV‐2 neutralization assays to determine the efficacy of boost immunization and therapeutic antibodies to neutralize the dominant Omicron variant. We provide compelling evidence that the third vaccination with BNT162b2 increases the amount of neutralizing serum antibodies against Delta and Omicron variants, albeit to a lower degree when compared to the parental Wuhan strain. Therefore, a third vaccination is warranted to increase titers of protective serum antibodies, especially in the case of the Omicron variant. We also found that most clinically approved and otherwise potent therapeutic antibodies against the Delta variant failed to recognize and neutralize the Omicron variant. In contrast, some antibodies under preclinical development potentially neutralized the Omicron variant. Our studies also support using a flow cytometry‐based antibody binding assay to rapidly monitor therapeutic candidates and serum titers against emerging SARS‐CoV‐2 variants. [ABSTRACT FROM AUTHOR]

WHICH ANTIVIRAL TREATMENT OPTIONS ARE SUITABLE FOR THERAPY OF PATIENTS INFECTED WITH THE OMIC... Treatment with recombinant monoclonal antibodies (mAbs) that neutralize SARS-CoV-2 can reduce the risk for severe disease. In contrast, neutralization of the Omicron variant is dramatically reduced,1 indicating that immunity following infection by previously circulating SARS-CoV-2 variants provides little to no protection against the Omicron variant. Keywords: antibody; omicron; SARS-CoV-2; spike EN antibody omicron SARS-CoV-2 spike 1 3 3 05/31/22 20220501 NES 220501 The severe acute respiratory syndrome coronavirus 2 Omicron variant (B.1.1.529) swept the globe with breathtaking speed, rapidly displacing the Delta variant and causing record numbers of new infections. [Extracted from the article]