A new polysaccharide platform constructs self-adjuvant nanovaccines to enhance immune responses.

BACKGROUND: Nanovaccines have shown the promising potential in controlling and eradicating the threat of infectious diseases worldwide. There has been a great need in developing a versatile strategy to conveniently construct diverse types of nanovaccines and induce potent immune responses. To that end, it is critical for obtaining a potent self-adjuvant platform to assemble with different types of antigens into nanovaccines. RESULTS: In this study, we identified a new natural polysaccharide from the rhizomes of Bletilla striata (PRBS), and used this polysaccharide as a platform to construct diverse types of nanovaccines with potent self-adjuvant property. In the construction process of SARS-CoV-2 nanovaccine, PRBS molecules and RBD protein antigens were assembled into ~ 300 nm nanoparticles by hydrogen bond. For HIV nanovaccine, hydrophobic effect dominantly drove the co-assembly between PRBS molecules and Env expression plasmid into ~ 350 nm nanospheres. Importantly, PRBS can potently activate the behaviors and functions of multiple immune cells such as macrophages, B cells and dendritic cells. Depending on PRBS-mediated immune activation, these self-adjuvant nanovaccines can elicit significantly stronger antigen-specific antibody and cellular responses in vivo, in comparison with their corresponding traditional vaccine forms. Moreover, we also revealed the construction models of PRBS-based nanovaccines by analyzing multiple assembly parameters such as bond energy, bond length and interaction sites. CONCLUSIONS: PRBS, a newly-identified natural polysaccharide which can co-assemble with different types of antigens and activate multiple critical immune cells, has presented a great potential as a versatile platform to develop potent self-adjuvant nanovaccines.

The optimal interval before receiving SARS-COV-2 vaccination for patients who have received Anti-CD 20 monoclonal antibodies.

The optimal interval before receiving SARS-COV-2 vaccination for patients who have received anti-CD 20 monoclonal antibodies remains unclear. We considered original studies up to 29 October 2022 and conducted searches in Embase,Medrxiv, PubMed, and SSRN. We excluded search results that did not match our research question's subject. Human immune response outcomes were analysed inpatients who had previously received anti-CD20 antibody therapy. We analyzed the collected results using sensitivity curves and forest plots. Twenty-eight studies with a total of 1455 subjects receiving anti-CD20 monoclonal antibodies were included in the present analysis. The humoral immune response rates to the time between the last anti-CD20 treatment and vaccination for 3-6 months, 6 months,6-9 months, and 9-12 months were 0.23 (95% CI 0.14 to 0.36), 0.36 (95% CI 0.19 to 0.58), 0.49 (95% CI 0.35 to 0.64) and 0.64 (95% CI 0.48 to 0.77),respectively. The humoral immune response rates were.16 (95% CI 0.03 to 0.57) when B cell was 0/ul, and 0.49 (95% CI 0.38 to 0.61)when B cells were more than 5/ul. The humoral immune response rate for multiple sclerosis was 0.39 (95% CI 0.22 to 0.60) and 0.48 (95% CI 0.29 to 0.68) for B-cell non-Hodgkin lymphoma. The area underneath the curve(AUC) was 0.69 with a cut-off value of 5.5 months. The present results suggested that the optimal interval for SARS-COV-2 vaccination after the final dose of anti-CD20 monoclonal antibody was 5.5 months.

Punicalagin as an allosteric NSP13 helicase inhibitor potently suppresses SARS-CoV-2 replication in vitro.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) helicase NSP13 plays a conserved role in the replication of coronaviruses and has been identified as an ideal target for the development of antiviral drugs against SARS-CoV-2. Here, we identify a novel NSP13 helicase inhibitor punicalagin (PUG) through high-throughput screening. Surface plasmon resonance (SPR)-based analysis and molecular docking calculation reveal that PUG directly binds NSP13 on the interface of domains 1A and 2A, with a KD value of 21.6 nM. Further biochemical and structural analyses suggest that PUG inhibits NSP13 on ATP hydrolysis and prevents it binding to DNA substrates. Finally, the antiviral studies show that PUG effectively suppresses the SARS-CoV-2 replication in A549-ACE2 and Vero cells, with EC50 values of 347 nM and 196 nM, respectively. Our work demonstrates the potential application of PUG in the treatment of coronavirus disease 2019 (COVID-19) and identifies an allosteric inhibition mechanism for future drug design targeting the viral helicases.

Research on Kinematics Analysis and Trajectory Planning of Novel EOD Manipulator

To address the problems of mismatch, poor flexibility and low accuracy of ordinary manipulators in the complex special deflagration work process, this paper proposes a new five-degree-of-freedom (5-DOF) folding deflagration manipulator. Firstly, the overall structure of the explosion-expulsion manipulator is introduced. The redundant degrees of freedom are formed by the parallel joint axes of the shoulder joint, elbow joint and wrist pitching joint, which increase the flexibility of the mechanism. Aiming at a complex system with multiple degrees of freedom and strong coupling of the manipulator, the virtual joint is introduced, the corresponding forward kinematics model is established by D–H method, and the inverse kinematics solution of the manipulator is derived by analytical method. In the MATLAB platform, the workspace of the manipulator is analyzed by Monte Carlo pseudo-random number method. The quintic polynomial interpolation method is used to simulate the deflagration task in joint space. Finally, the actual prototype experiment is carried out using the data obtained by simulation. The trajectory planning using the quintic polynomial interpolation method can ensure the smooth movement of the manipulator and high accuracy of operation. Furthermore, the trajectory is basically consistent with the simulation trajectory, which can realize the work requirements of putting the object into the explosion-proof tank. The new 5-DOF folding deflagration manipulator designed in this paper has stable motion and strong robustness, which can be used for deflagration during the COVID-19 epidemic.

Cryo-electron Microscopy Structure of the Swine Acute Diarrhea Syndrome Coronavirus Spike Glycoprotein Provides Insights into Evolution of Unique Coronavirus Spike Proteins.

Coronaviruses (CoV) have caused a number of major epidemics in humans and animals, including the current pandemic of coronavirus disease 2019 (COVID-19), which has brought a renewed focus on the evolution and interspecies transmission of coronaviruses. Swine acute diarrhea syndrome coronavirus (SADS-CoV), which was recently identified in piglets in southern China, is an alphacoronavirus that originates from the same genus of horseshoe bats as severe acute respiratory syndrome CoV (SARS-CoV) and that was reported to be capable of infecting cells from a broad range of species, suggesting a considerable potential for interspecies transmission. Given the importance of the coronavirus spike (S) glycoprotein in host range determination and viral entry, we report a cryo-electron microscopy (cryo-EM) structure of the SADS-CoV S trimer in the prefusion conformation at a 3.55-Å resolution. Our structure reveals that the SADS-CoV S trimer assumes an intrasubunit quaternary packing mode in which the S1 subunit N-terminal domain (S1-NTD) and the S1 subunit C-terminal domain (S1-CTD) of the same protomer pack together by facing each other in the lying-down state. SADS-CoV S has several distinctive structural features that may facilitate immune escape, such as a relatively compact architecture of the S trimer and epitope masking by glycan shielding. Comparison of SADS-CoV S with the spike proteins of the other coronavirus genera suggested that the structural features of SADS-CoV S are evolutionarily related to those of the spike proteins of the other genera rather than to the spike protein of a typical alphacoronavirus. These data provide new insights into the evolutionary relationship between spike glycoproteins of SADS-CoV and those of other coronaviruses and extend our understanding of their structural and functional diversity.IMPORTANCE In this article, we report the atomic-resolution prefusion structure of the spike protein from swine acute diarrhea syndrome coronavirus (SADS-CoV). SADS-CoV is a pathogenic alphacoronavirus that was responsible for a large-scale outbreak of fatal disease in pigs and that was reported to be capable of interspecies transmission. We describe the overall structure of the SADS-CoV spike protein and conducted a detailed analysis of its main structural elements. Our results and analyses are consistent with those of previous phylogenetic studies and suggest that the SADS-CoV spike protein is evolutionarily related to the spike proteins of betacoronaviruses, with a strong similarity in S1-NTDs and a marked divergence in S1-CTDs. Moreover, we discuss the possible immune evasion strategies used by the SADS-CoV spike protein. Our study provides insights into the structure and immune evasion strategies of the SADS-CoV spike protein and broadens the understanding of the evolutionary relationships between coronavirus spike proteins of different genera.