ABSTRACT
We investigated ChAdOx1 nCoV-19 (AZD1222) vaccine efficacy against SARS-CoV-2 variants of concern (VOCs) B.1.1.7 and B.1.351 in Syrian hamsters. We previously showed protection against SARS-CoV-2 disease and pneumonia in hamsters vaccinated with a single dose of ChAdOx1 nCoV-19. Here, we observe a 9.5-fold reduction of virus neutralizing antibody titer in vaccinated hamster sera against B.1.351 compared to B.1.1.7. Vaccinated hamsters challenged with B.1.1.7 or B.1.351 do not lose weight compared to control animals. In contrast to control animals, the lungs of vaccinated animals do not show any gross lesions. Minimal to no viral subgenomic RNA (sgRNA) and no infectious virus can be detected in lungs of vaccinated animals. Histopathological evaluation shows extensive pulmonary pathology caused by B.1.1.7 or B.1.351 replication in the control animals, but none in the vaccinated animals. These data demonstrate the effectiveness of the ChAdOx1 nCoV-19 vaccine against clinical disease caused by B.1.1.7 or B.1.351 VOCs.
Subject(s)
COVID-19 Vaccines/immunology , COVID-19/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Administration, Intranasal , Amino Acid Substitution , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/virology , ChAdOx1 nCoV-19 , Female , Lung/immunology , Lung/pathology , Lung/virology , Mesocricetus , Spike Glycoprotein, Coronavirus/immunology , VaccinationABSTRACT
BACKGROUND: SARS-CoV-2 proteins binding human mRNAs (SPBRs) have been proven to regulate a variety of tumor-related functions in different types of cancer. However, their biological roles and potential mechanisms in clear cell renal cell carcinoma (ccRCC) are still elusive. Herein, we investigate the expression and prognostic value of SPBRs in ccRCC through bioinformatics methods. METHODS: Data downloaded from the Cancer Genome Atlas (TCGA) database was used to screen differentially expressed SPBRs (DE-SPBRs) between ccRCC samples and noncancerous samples. Metascape was utilized to perform function and pathway enrichment analyses of these DE-SPBRs. Kaplan-Meier method of overall survival (OS) was used to assess the prognostic value of DE-SPBRs in ccRCC patients. Univariate and multivariate Cox regression analyses were applied to identify candidate SPBRs, which were independently associated with overall survival of ccRCC patients. Subsequently, several internationally renowned databases were employed to conduct a comprehensive analysis of candidate SPBRs to further investigate their roles and mechanisms in ccRCC. RESULTS: A total of 33 DE-SPBRs, including 18 upregulated SPBRs and 17 downregulated SPBRs, were screened between ccRCC samples and noncancerous samples. Among them, two candidate SPBRs, KDELC1 and TRMT1, were identified. Additionally, we observed that upregulated KDELC1/TRMT1 expression in ccRCC at both gene and protein levels was significantly associated with clinicopathological features. Furthermore, we found that KDELC1/TRMT1 genetic mutation has an unfavorable influence on prognosis of patients with ccRCC. Functional enrichment analysis revealed that KDELC1/TRMT1 was closely enriched in several vital biological processes and pathways. Finally, we noticed that KDELC1/TRMT1 was remarkably associated with immune infiltrates. CONCLUSION: In summary, we screened DE-SPBRs of ccRCC, which were enriched mainly in various biological and signaling pathways with tumor progression. Furthermore, we identified two candidate DE-SPBRs (KDELC1 and TRMT1), which could serve as promising biomarkers and therapeutic targets of patients with ccRCC.
ABSTRACT
Objective: To investigate the features of liver injury in patients with coronavirus disease 2019 (COVID -19), and to provide a reference for clinical diagnosis and treatment.
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 20191,2 and is responsible for the coronavirus disease 2019 (COVID-19) pandemic3. Vaccines are an essential countermeasure and are urgently needed to control the pandemic4. Here we show that the adenovirus-vector-based vaccine ChAdOx1 nCoV-19, which encodes the spike protein of SARS-CoV-2, is immunogenic in mice and elicites a robust humoral and cell-mediated response. This response was predominantly mediated by type-1 T helper cells, as demonstrated by the profiling of the IgG subclass and the expression of cytokines. Vaccination with ChAdOx1 nCoV-19 (using either a prime-only or a prime-boost regimen) induced a balanced humoral and cellular immune response of type-1 and type-2 T helper cells in rhesus macaques. We observed a significantly reduced viral load in the bronchoalveolar lavage fluid and lower respiratory tract tissue of vaccinated rhesus macaques that were challenged with SARS-CoV-2 compared with control animals, and no pneumonia was observed in vaccinated SARS-CoV-2-infected animals. However, there was no difference in nasal shedding between vaccinated and control SARS-CoV-2-infected macaques. Notably, we found no evidence of immune-enhanced disease after viral challenge in vaccinated SARS-CoV-2-infected animals. The safety, immunogenicity and efficacy profiles of ChAdOx1 nCoV-19 against symptomatic PCR-positive COVID-19 disease will now be assessed in randomized controlled clinical trials in humans.