ABSTRACT
Coronaviruses (CoVs) are nonsegmented, single-stranded, positive-sense RNA viruses highly pathogenic to humans. Some CoVs are known to cause respiratory and intestinal diseases, posing a threat to the global public health. Against this backdrop, it is of critical importance to develop safe and effective vaccines against these CoVs. This review discusses human vaccine candidates in any stage of development and explores the viral characteristics, molecular epidemiology, and immunology associated with CoV vaccine development. At present, there are many obstacles and challenges to vaccine research and development, including the lack of knowledge about virus transmission, pathogenesis, and immune response, absence of the most appropriate animal models.
Subject(s)
COVID-19 Vaccines/biosynthesis , COVID-19/prevention & control , Coronavirus Infections/prevention & control , Severe Acute Respiratory Syndrome/prevention & control , Spike Glycoprotein, Coronavirus/immunology , Animals , COVID-19/immunology , COVID-19/virology , Camelus , Coronavirus Infections/immunology , Coronavirus Infections/virology , Cricetulus , Disease Models, Animal , Humans , Macaca mulatta , Mice , Middle East Respiratory Syndrome Coronavirus/drug effects , Middle East Respiratory Syndrome Coronavirus/immunology , Severe acute respiratory syndrome-related coronavirus/drug effects , Severe acute respiratory syndrome-related coronavirus/immunology , SARS-CoV-2/drug effects , SARS-CoV-2/immunology , Severe Acute Respiratory Syndrome/immunology , Severe Acute Respiratory Syndrome/virology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Vaccines, Subunit , Vaccines, Synthetic/biosynthesis , Vaccines, Virus-Like Particle/biosynthesis , mRNA VaccinesABSTRACT
BACKGROUND: The virological or clinical relapse is common in chronic hepatitis B (CHB) patients after stopping long-term nucleos(t)ide analogue (NA) therapy. Soluble growth stimulation expressed gene 2 (sST2), one of the Toll-like/interleukin-1 receptor members, is involved in a variety of inflammatory processes and immune responses. However, the expression and function of serum sST2 in CHB patients after stopping NA treatment remains unknown. METHODS: A total of 91 non-cirrhotic Asian patients with CHB who discontinued NA therapy according to international guidelines were prospectively followed up to 240 weeks. All patients were divided into clinical relapse group and non-clinical relapse (including sustained virological response and only virological relapse) group according HBV DNA and ALT levels. The serum levels of sST2 of all participants were determined by ELISA and compared between each two groups. RESULTS: Clinical relapse occurred in 26 patients and virological relapse occurred in 57 patients. We found that there was a positive correlation between sST2 expression and HBsAg, ALT, HBV DNA, and anti-HBc levels in CHB patients after discontinuation of NA treatment. Levels of serum sST2 in clinical relapse patients showed a rising trend and most patients showed peak sST2 levels at the point of clinical relapse. Moreover, the sST2 levels of clinical relapse group at week 12, week 24 and week 48 were relatively higher than non-clinical relapse group. However, the level of sST2 at the end of treatment was not an effective biological marker for the early prediction of clinical relapse after discontinuation of long-term NA therapy. CONCLUSIONS: In conclusion, we found that an increase in sST2 in clinical relapse patients might be associated with an inflammation-related immune response after discontinuation of NA treatment. TRIAL REGISTRATION: The trial was retrospectively registered at Chinese Clinical Trial Registry: ChiCTR-OOC-17013970 . Registration date: December 15, 2017.
Subject(s)
Antiviral Agents/therapeutic use , Hepatitis B, Chronic/drug therapy , Interleukin-1 Receptor-Like 1 Protein/blood , Adult , Biomarkers/blood , Female , Hepatitis B e Antigens/blood , Hepatitis B virus/genetics , Hepatitis B, Chronic/blood , Humans , Male , Prospective Studies , Recurrence , Sustained Virologic Response , Treatment OutcomeABSTRACT
Hepatitis B virus-associated (HBV(+)) hepatocellular carcinoma (HCC) accounts for a large proportion of liver cancer with poor clinical outcomes and treatment options. However, the underlying molecular mechanisms are still poorly understood. To explore potential key genes in the development of HBV(+)HCC, four series of data (GSE14520, GSE94660, GSE25599, and GSE55092) derived from Gene Expression Omnibus database were analyzed. Totally, 84 upregulated and 46 downregulated common differentially expressed genes (DEGs) were discovered. Gene ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses showed that these DEGs were mainly enriched in cell division and DNA replication biological processes, nucleoplasm and microtubule cellular components, protein-binding molecular functions, and cell cycle and DNA replication pathways. Through protein-protein interaction analysis, 10 hub DEGs with the highest degree of connectivity were indicated, including TOP2A, CDC20, MAD2L1, BUB1B, RFC4, CCNB1, CDKN3, CCNB2, TPX2, and FEN1. Kaplan-Meier analysis revealed that high expression of TOP2A and CDC20 was associated with poor overall survival, relapse-free survival, and high serum alpha-fetoprotein level in HBV(+)HCC. In conclusion, TOP2A and CDC20 were two potential key genes for HBV(+)HCC. Their value in the diagnosis and treatment of HBV(+)HCC requires further investigation.
