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1.
Vaccine ; 41(18): 3003-3010, 2023 05 02.
Article in English | MEDLINE | ID: covidwho-2296670

ABSTRACT

INTRODUCTION: Here, we systematically assessed the safety and immunogenicity of the heterologous ChAd/BNT vaccination regimens. MATERIALS AND METHODS: We evaluated the immunogenicity by the geometric mean titers ratio (GMTR) of the neutralizing antibody and anti-spike IgG. The safety of heterologous ChAd/BNT vaccination was evaluated using the pooled risk ratios (RRs) calculated by the random-effects model about the adverse events. Our study was registered with PROSPERO, CRD42021265165. RESULTS: Eleven studies were included in the analyses. Compared to the homologous ChAd/ChAd vaccination, the heterologous ChAd/BNT vaccination showed significantly higher immunogenicity in terms of the neutralizing antibody and GMTR of anti-spike IgG, but at the same time displayed higher incidence of total adverse reactions, especially for the local adverse reactions. Moreover, heterologous ChAd/BNT vaccination showed similar immunogenicity to the homologous BNT/BNT vaccination (GMTR of neutralizing antibody and anti-spike IgG) and similar safety. DISCUSSION: Heterologous ChAd/BNT vaccination showed robust immunogenicity and tolerable safety.


Subject(s)
BNT162 Vaccine , COVID-19 , Humans , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Vaccination/adverse effects , Antibodies, Neutralizing , Immunoglobulin G , Antibodies, Viral
2.
Vaccine ; 2023.
Article in English | EuropePMC | ID: covidwho-2263396

ABSTRACT

Introduction Here, we systematically assessed the safety and immunogenicity of the heterologous ChAd/BNT vaccination regimens. Materials and Methods We evaluated the immunogenicity by the geometric mean titers ratio (GMTR) of the neutralizing antibody and anti-spike IgG. The safety of heterologous ChAd/BNT vaccination was evaluated using the pooled risk ratios (RRs) calculated by the random-effects model about the adverse events. Our study was registered with PROSPERO, CRD42021265165. Results Eleven studies were included in the analyses. Compared to the homologous ChAd/ChAd vaccination, the heterologous ChAd/BNT vaccination showed significantly higher immunogenicity in terms of the neutralizing antibody and GMTR of anti-spike IgG, but at the same time displayed higher incidence of total adverse reactions, especially for the local adverse reactions. Moreover, heterologous ChAd/BNT vaccination showed similar immunogenicity to the homologous BNT/BNT vaccination (GMTR of neutralizing antibody and anti-spike IgG) and similar safety. Discussion Heterologous ChAd/BNT vaccination showed robust immunogenicity and tolerable safety. Running title: heterologous COVID-19 vaccination outcomes

3.
J Med Chem ; 65(24): 16252-16267, 2022 12 22.
Article in English | MEDLINE | ID: covidwho-2160140

ABSTRACT

The two proteases, PLpro and Mpro, of SARS-CoV-2 are essential for replication of the virus. Using a structure-based co-pharmacophore screening approach, we developed a novel dual-targeted inhibitor that is equally potent in inhibiting PLpro and Mpro of SARS-CoV-2. The inhibitor contains a novel warhead, which can form a covalent bond with the catalytic cysteine residue of either enzyme. The maximum rate of the covalent inactivation is comparable to that of the most potent inhibitors reported for the viral proteases and covalent inhibitor drugs currently in clinical use. The covalent inhibition appears to be very specific for the viral proteases. The inhibitor has a potent antiviral activity against SARS-CoV-2 and is also well tolerated by mice and rats in toxicity studies. These results suggest that the inhibitor is a promising lead for development of drugs for treatment of COVID-19.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Mice , Rats , Papain , Cysteine Endopeptidases/chemistry , Viral Nonstructural Proteins , Peptide Hydrolases , Viral Proteases , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , Protease Inhibitors/pharmacology , Protease Inhibitors/therapeutic use , Protease Inhibitors/chemistry , Molecular Docking Simulation
4.
Biomed Res Int ; 2022: 3510423, 2022.
Article in English | MEDLINE | ID: covidwho-2020494

ABSTRACT

Purpose: Aurantiamide acetate (AA) is a dipeptide derivative with complex pharmacological activities and remarkable effects on preventing and treating various diseases. In the current study, we aimed to investigate whether AA can exert protective effects in a mouse model of ALI induced by LPS. Materials and Methods: In this model, mice were given intranasal LPS for 3 days prior to receiving AA (2.5, 5, and 10 mg/kg) via oral gavage. An assessment of histopathological changes was performed by hematoxylin and eosin (HE). Proinflammatory cytokines were detected in bronchoalveolar lavage fluids (BALFs) by enzyme-linked immunosorbent assays (ELISAs). The effects of AA on protein expression of NF-κB and PI3K/AKT signaling pathways were determined by Western blot. In addition, lung wet/dry (W/D) weight ratio, myeloperoxidase (MPO) activity, cell counts, and protein content were also measured. Results: According to results, AA pretreatment significantly reduced lung pathological changes, W/D ratio, MPO activity, and protein content. Additionally, AA resulted in a significant reduction in the number of total cells, neutrophils, and proinflammatory cytokines in the BALF after LPS stimulation. The subsequent study revealed that pretreatment with AA dose dependently suppressed LPS-induced activation of NF-κB as well as PI3K/AKT phosphorylation. Conclusion: The results indicated that the AA had a protective effect on LPS-induced ALI in mice and could be a potential drug for ALI.


Subject(s)
Acute Lung Injury , Pneumonia , Acute Lung Injury/chemically induced , Acute Lung Injury/drug therapy , Acute Lung Injury/metabolism , Animals , Bronchoalveolar Lavage Fluid/chemistry , Cytokines/metabolism , Dipeptides/pharmacology , Lipopolysaccharides/adverse effects , Lung/pathology , Mice , Mice, Inbred BALB C , NF-kappa B/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Pneumonia/pathology , Proto-Oncogene Proteins c-akt/metabolism
5.
Biomed Res Int ; 2021: 8112783, 2021.
Article in English | MEDLINE | ID: covidwho-1378089

ABSTRACT

Long noncoding RNAs (lncRNAs) have been reported to participate in regulating many biological processes, including immune response to influenza A virus (IAV). However, the association between lncRNA expression profiles and influenza infection susceptibility has not been well elucidated. Here, we analyzed the expression profiles of lncRNAs, miRNAs, and mRNAs among IAV-infected adult rat (IAR), normal adult rat (AR), IAV-infected junior rat (IJR), and normal junior rat (JR) by RNA sequencing. Compared with differently expressed lncRNAs (DElncRNAs) between AR and IAR, 24 specific DElncRNAs were found between IJR and JR. Then, based on the fold changes and P value, the top 5 DElncRNAs, including 3 upregulated and 2 downregulated lncRNAs, were chosen to establish a ceRNA network for further disclosing their regulatory mechanisms. To visualize the differentially expressed genes in the ceRNA network, GO and KEGG pathway analysis was performed to further explore their roles in influenza infection of junior rats. The results showed that the downregulated DElncRNA-target genes were mostly enriched in the IL-17 signaling pathway. It indicated that the downregulated lncRNAs conferred the susceptibility of junior rats to IAV via mediating the IL-17 signaling pathway.


Subject(s)
Influenza A virus/pathogenicity , MicroRNAs/genetics , Orthomyxoviridae Infections/genetics , RNA, Long Noncoding/genetics , RNA, Messenger/genetics , Animals , Disease Models, Animal , Disease Susceptibility , Gene Expression Profiling , Influenza A virus/isolation & purification , Interleukin-17/genetics , Interleukin-17/immunology , MicroRNAs/immunology , Orthomyxoviridae Infections/immunology , Orthomyxoviridae Infections/pathology , Orthomyxoviridae Infections/virology , RNA, Long Noncoding/immunology , RNA, Messenger/immunology , Rats , Rats, Sprague-Dawley
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