Passive immunotherapy with monoclonal antibodies (mAbs) is an efficacious treatment for Ebola virus (EBOV) infections in animal models and humans. Understanding what constitutes a protective response is critical for the development of novel therapeutic strategies. We generated an EBOV-glycoprotein-pseudotyped Human immunodeficiency virus to develop sensitive neutralizing and antibody-dependent cellular cytotoxicity (ADCC) assays as well as a bioluminescent-imaging-based mouse infection model that does not require biosafety level 4 containment. The in vivo treatment efficiencies of three novel anti-EBOV mAbs at 12 h post-infection correlated with their in vitro anti-EBOV ADCC activities, without neutralizing activity. When they were treated with these mAbs, natural killer cell (NK)-deficient mice had lower viral clearance than WT mice, indicating that the anti-EBOV mechanism of the ADCC activity of these mAbs is predominantly mediated by NK cells. One potent anti-EBOV mAb (M318) displayed unprecedented neutralizing and ADCC activities (neutralization IC50, 0.018 μg/ml; ADCC EC50, 0.095 μg/ml). These results have important implications for the efficacy of antiviral drugs and vaccines as well as for pathogenicity studies of EBOV.

SARS-CoV-2 and SARS-CoV share a common human receptor ACE2. Protein-protein interaction structure modeling indicates that spike-RBD of the two viruses also has similar overall binding conformation and binding free energy to ACE2. In vitro assays using recombinant ACE2 proteins and ACE2 expressing cells confirmed the two coronaviruses' similar binding affinities to ACE2. The above studies provide experimental supporting evidences and possible explanation for the high transmissibility observed in the SARS-CoV-2 outbreak. Potent ACE2-blocking SARS-CoV neutralizing antibodies showed limited cross-binding and neutralizing activities to SARS-CoV-2. ACE2-non-blocking SARS-CoV RBD antibodies, though with weaker neutralizing activities against SARS-CoV, showed positive cross-neutralizing activities to SARS-CoV-2 with an unknown mechanism. These findings suggest a trade-off between the efficacy and spectrum for therapeutic antibodies to different coronaviruses, and hence highlight the possibilities and challenges in developing broadly protecting antibodies and vaccines against SARS-CoV-2 and its future mutants.

32The COVID-19 pandemic caused by the SARS-CoV-2 virus has resulted in an 33 unprecedented public health crisis. There are no approved vaccines or therapeutics for 34 treating COVID-19. Here we reported a humanized monoclonal antibody, H014, 35 efficiently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as 36 authentic SARS-CoV-2 at nM level by engaging the S receptor binding domain 37 (RBD). Importantly, H014 administration reduced SARS-CoV-2 titers in the infected 38 lungs and prevented pulmonary pathology in hACE2 mouse model. Cryo-EM 39 characterization of the SARS-CoV-2 S trimer in complex with the H014 Fab fragment 40 unveiled a novel conformational epitope, which is only accessible when the RBD is in 41 open conformation. Biochemical, cellular, virological and structural studies 42 demonstrated that H014 prevents attachment of SARS-CoV-2 to its host cell receptors. 43 Epitope analysis of available neutralizing antibodies against SARS-CoV and 44 SARS-CoV-2 uncover broad cross-protective epitopes. Our results highlight a key 45 role for antibody-based therapeutic interventions in the treatment of COVID-19. 46 47 48

With the emergence and rapid spread of new pandemic variants, especially variants of concern (VOCs), the development of next-generation vaccines with broad-spectrum neutralizing activities is of great importance. In this study, SCTV01C, a clinical stage bivalent vaccine based on trimeric spike extracellular domain (S-ECD) of SARS-CoV-2 variants Alpha (B.1.1.7) and Beta (B.1.351) with a squalene-based oil-in-water adjuvant was evaluated in comparison to its two corresponding (Alpha and Beta) monovalent vaccines in mouse immunogenicity studies. The two monovalent vaccines induced potent neutralizing antibody responses against the antigen-matched variants, but drastic reductions in neutralizing antibody titers against antigen-mismatched variants were observed. In comparison, the bivalent vaccine SCTV01C induced relatively higher and broad-spectrum cross-neutralizing activities against various SARS-CoV-2 variants, including the D614G variant, VOCs (B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.1.529), variants of interest (VOIs) (C.37, B.1.621), variants under monitoring (VUMs) (B.1.526, B.1.617.1, B.1.429, C.36.3) and other variants (B.1.618, 20I/484Q). All three vaccines elicited potent Th1-biased T-cell immune responses. These results provide direct evidence that variant-based multivalent vaccines could play important roles in addressing the critical issue of reduced protective efficacy against the existing and emerging SARS-CoV-2 variants.

The ongoing COVID‐19 pandemic caused by SARS‐CoV‐2 has led to millions of deaths worldwide. Streptococcus pneumoniae (S. pneumoniae) remains a major cause of mortality in underdeveloped countries. A vaccine that prevents both SARS‐CoV‐2 and S. pneumoniae infection represents a long‐sought “magic bullet”. Herein, a nanoparticle vaccine, termed SCTV01B, is rationally developed by using the capsular polysaccharide of S. pneumoniae serotype 14 (PPS14) as the backbone to conjugate with the recombinant receptor‐binding domain (RBD) of the SARS‐CoV‐2 spike protein. The final formulation of conjugated nanoparticles in the network structure exhibits high thermal stability. Immunization with SCTV01B induces potent humoral and Type 1/Type 2 T helper cell (Th1/Th2) cellular immune responses in mice, rats, and rhesus macaques. In particular, SCTV01B‐immunized serum not only broadly cross‐neutralizes all SARS‐CoV‐2 variants of concern (VOCs), including the most recent Omicron variant, but also shows high opsonophagocytic activity (OPA) against S. pneumoniae serotype 14. Finally, SCTV01B vaccination confers protection against challenges with the SARS‐CoV‐2 mouse‐adapted strain and the original strain in established murine models. Collectively, these promising preclinical results support further clinical evaluation of SCTV01B, highlighting the potency of polysaccharide‐RBD‐conjugated nanoparticle vaccine platforms for the development of vaccines for COVID‐19 and other infectious diseases.

SUMMARY: Enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) are members of the Picornaviridae family and are considered the main causative agents of hand, foot and mouth disease (HFMD). In recent decades large HFMD outbreaks caused by EV71 and CVA16 have become significant public health concerns in the Asia-Pacific region. Vaccines and antiviral drugs are unavailable to prevent EV71 and CVA16 infection. In the current study, a chimeric antibody targeting a highly conserved peptide in the EV71 VP4 protein was isolated by using a phage display technique. The antibody showed crossneutralizing capability against EV71 and CVA16 in vitro. The results suggest that this phage displayderived antibody will have great potential as a broad neutralizing antibody against EV71 and CVA16 after affinity maturation and humanization.

SCTA01 is a novel monoclonal antibody with promising prophylactic and therapeutic potential for COVID-19. This study aimed to evaluate the safety, tolerability, pharmacokinetics (PK) and immunogenicity of SCTA01 in healthy adults. This was a randomized, double-blind, placebo-controlled, dose-escalation phase I clinical trial. Healthy adults were randomly assigned into the following four cohorts, Cohort 1 (n=5, 3:2), Cohort 2 (n=8, 6:2), Cohort 3 and Cohort 4 (both n=10, 8:2), to receive SCTA01 (5, 15, 30 and 50 mg/kg, respectively) versus placebo. All participants were followed up for clinical, laboratory, PK and immunogenicity assessments for 84 days. The primary outcomes were the dose-limiting toxicity (DLT) and maximal tolerable dose (MTD), and the secondary outcomes included PK parameters, immunogenicity and adverse events (AE). Of the 33 participants, 18 experienced treatment-related AEs; the frequency was 52.0% (13/25) in participants receiving SCTA01 and 62.5% (5/8) in those receiving placebo. All AEs were mild. There was no serious AE or death. No DLT was reported, and MTD of SCTA01 was not reached. SCTA01 with a dose range 5-50mg/kg had nearly linear dose-proportional increases in C max and AUC parameters. An anti-drug antibody response was detected in four (16.0%) participants receiving SCTA01, with low titers, between the baseline and day 28, but all became negative later. In conclusion, SCTA01 up to 50mg/kg was safe and well-tolerated in healthy participants. Its PK parameters were nearly linear dose-proportional.

When taking pictures of electronic screens or objects with high-frequency textures, people often run across colorful rainbow patterns that are known as ''moire'', seriously affecting the image quality and subsequent processing. Current methods for removing moire patterns mostly extract multiscale information by downsampling pooling layers, which may inevitably cause information loss. To address this issue, this paper proposes a demoireing method in the wavelet domain. By employing both discrete wavelet transform (DWT) and inverse discrete wavelet transform (IDWT) instead of traditional downsampling and upsampling, this method can effectively increase the network receptive field without information loss. In addition, to further reconstruct more details of moire patterns, this paper proposes an efficient attention fusion module (EAFM). With a combination of efficient channel attention, spatial attention and local residual learning, this module can self-adaptively learn various weights of feature information at different levels and inspire the network to focus more on effective information such as moire details to improve learning and demoireing performance. Extensive experiments based on public datasets have shown that this suggested method can efficiently remove moire patterns and has a good quantitative and qualitative performance.INDEX TERMS Demoire, deep learning, wavelet transform, attention mechanism.