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.

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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. K E Y W O R D S animal model, coronavirus, receptor-binding domain, spike protein, vaccine 1 | INTRODUCTION Coronaviruses (CoVs) are a large family of viruses with some causing mild to moderate illnesses like the common cold and others bringing severe diseases such as Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV). At the end of 2019, emerging infections caused by a novel CoV were reported in Wuhan, China. Most of the early reported cases came from the South China Seafood Wholesale Market in Wuhan, China, which is now closed and disinfected. The virus was identified as a new CoV and officially named by The International Committee on Taxonomy of Viruses as SARS-CoV-2 (previously provisionally named 2019 novel coronavirus or 2019-nCoV by World Health Organization [WHO]), and the disease caused by SARS-CoV-2 received its official name as COVID-19 later on February 11, 2020. 1 As of July 29, 2020, there were 16,341,920 confirmed COVID-19 cases worldwide, including 650,805 deaths. According to the WHO, 226,783 new cases and 4153 new deaths worldwide in the last 24 h. 2 Since the beginning of the new millennium, the rapid emergence and spread of CoVs have caused a grave loss of life and property. One of the most famous examples is the SARS-CoV, which first appeared during the winter of 2002 and caused a viral respiratory illness, namely the SARS. 3,4 The SARS epidemic had serious consequences in 29 regions and countries, with 8096 people being infected worldwide and the mortality rate reaching 9.6%. 5 Later in 2012, the MERS-CoV was first identified in a 60-year-old man who lived in the Kingdom of