Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 6 de 6
Filter
1.
Advanced Materials ; 34(21):2270160, 2022.
Article in English | Wiley | ID: covidwho-1866500

ABSTRACT

Nanoparticle Vaccines In article number 2200443, Liangzhi Xie, Chengfeng Qin, and co-workers develop a novel bivalent nanoparticle vaccine that confers protection against infection of multiple SARS-CoV-2 variants and Streptococcus pneumoniae. This universal polysaccharide?protein-conjugated vaccine platform provides a powerful tool to fight against cocirculating viral and bacterial pathogens worldwide.

2.
Vaccines (Basel) ; 10(5)2022 Apr 29.
Article in English | MEDLINE | ID: covidwho-1820439

ABSTRACT

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.

3.
Adv Mater ; 34(21): e2200443, 2022 May.
Article in English | MEDLINE | ID: covidwho-1763176

ABSTRACT

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.


Subject(s)
COVID-19 , Nanoparticles , Vaccines , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Macaca mulatta/metabolism , Mice , Nanoparticles/chemistry , Pandemics , Polysaccharides , Rats , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Streptococcus pneumoniae/metabolism
4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315360

ABSTRACT

The main protease (Mpro) is one of the best-characterized drug targets among coronaviruses. In the current study, we adopted a multiple cross-docking strategy against different crystal structures of SARS-CoV-2 Mpro to perform computer-based high-throughput virtual screening of possible inhibitors from a drug database using Autodock Vina and SeeSAR software, combined with our in-house automatic processing scripts. The KDs between screened candidates and Mpro were determined using Biacore. Seven drugs were found to fit the substrate-binding pocket of Mpro with a stable conformation, showing high KDs that ranged from 6.79E-7 M to 5.20E-5 M. Finally, mutagenesis studies confirmed that these drugs interact with Mpro specifically, suggesting that our method was reliable and convincing. Given the safety of these old drugs, they may serve as promising candidates to treat the infection of SARS-CoV-2. Our results also provide rational explanations for the behaviour of five drugs evaluated in clinical trials.

6.
Natl Sci Rev ; 8(3): nwaa297, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-990776

ABSTRACT

Receptor recognition and subsequent membrane fusion are essential for the establishment of successful infection by SARS-CoV-2. Halting these steps can cure COVID-19. Here we have identified and characterized a potent human monoclonal antibody, HB27, that blocks SARS-CoV-2 attachment to its cellular receptor at sub-nM concentrations. Remarkably, HB27 can also prevent SARS-CoV-2 membrane fusion. Consequently, a single dose of HB27 conferred effective protection against SARS-CoV-2 in two established mouse models. Rhesus macaques showed no obvious adverse events when administrated with 10 times the effective dose of HB27. Cryo-EM studies on complex of SARS-CoV-2 trimeric S with HB27 Fab reveal that three Fab fragments work synergistically to occlude SARS-CoV-2 from binding to the ACE2 receptor. Binding of the antibody also restrains any further conformational changes of the receptor binding domain, possibly interfering with progression from the prefusion to the postfusion stage. These results suggest that HB27 is a promising candidate for immuno-therapies against COVID-19.

SELECTION OF CITATIONS
SEARCH DETAIL