Volume 06 · Issue 05 · 2024

《2030年免疫议程》在其建立有效免疫方案的多个战略优先事项中概述了国家、区域和地方各级研究人员、监管者和公共卫生官员能力建设的重要性[1].中国科学院大学的使命是专注于前沿科学和应用生物技术，应对国家发展和世界可持续发展的挑战，面向全球科技进步的前沿，在经济主战场上竞争，解决国家和人民生命健康的重大需求。一段时间以来，科学技术在控制感染、开发疫苗和促进药物研发（R&D）方面提供了强有力的支持，而对此的支持和延续为研究界提供了模型问题和解决方案。因此，这是我们科学方法背后的指导哲学[2].冠状病毒疾病2019（新冠肺炎）疫情也为中等收入国家政府敲响了警钟，要求它们建立国内疫苗相关能力，以应对疫情和当地人口的健康需求。虽然疫苗学培训课程在世界各地开展，但在总共33个已确定的疫苗学高级课程中，只有13个位于中低收入国家[3,4].培训分配的公平性差表明了发展中国家对疫苗学课程的需求，这些国家迫切需要高质量的免疫服务来填补全球疫苗覆盖率的最大缺口。短期培训课程的价值在全球范围内得到了广泛认可，特别是在中等收入国家，在政府、非政府组织、教育机构、行业和其他全球卫生行为者的支持下，每年都有越来越多的高级疫苗学课程在世界各地涌现。

Mpox is a zoonotic disease caused by the monkeypox virus (MPXV). Diagnosing and treating the disease has become a global health concern requiring close attention to its spread to non‐endemic regions. Clinical diagnosis is based on laboratory test results. Conventional detection techniques include real‐time quantitative polymerase chain reaction (qPCR), genome sequencing, antigen and antibody identification, and virus isolation. Nevertheless, these methods fall short of rapidly and efficiently identifying MPXV, as they require specialized training, specific laboratory environments, and professional‐grade equipment. Emerging technologies offer complementary advantages to meet diverse diagnostic needs, including various point‐of‐care testing (POCT) approaches and integrating biosensors with rapid detection techniques. This review discusses prospective future research avenues for MPXV detection, examining the advances and challenges of various detection techniques which may contribute to the ongoing elimination of mpox human‐to‐human transmission and serves as a reference for developing effective prevention and control strategies.

Biosafety hazards can trigger a host immune response after infection, invasion, or contact with the host. Whether infection with a microorganism results in disease or biosafety concerns depends to a large extent on the immune status of the population. Therefore, it is essential to investigate the immunological characteristics of the host and the mechanisms of biological threats and agents to protect the host more effectively. Emerging and re‐emerging infectious diseases, such as the current coronavirus disease 2019 (COVID‐19) pandemic, have raised concerns regarding both biosafety and immunology worldwide. Interdisciplinary studies involved in biosafety and immunology are relevant in many fields, including the development of vaccines and other immune interventions such as monoclonal antibodies and T‐cells, herd immunity (or population‐level barrier immunity), immunopathology, and multispecies immunity, i.e., animals and even plants. Meanwhile, advances in immunological science and technology are occurring rapidly, resulting in important research achievements that may contribute to the recognition of emerging biosafety hazards, as well as early warning, prevention, and defense systems. This review provides an overview of the interdisciplinary field of biosafety and immunology. Close collaboration and innovative application of immunology in the field of biosafety is becoming essential for human health.

Despite the availability of vaccines and antiviral treatments, the continued emergence of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants and breakthrough infections underscores the need for new, potent antiviral therapies. In a previous study, we established a transcription and replication‐competent SARS‐CoV‐2 virus‐like particle (trVLP) system that recapitulates the complete viral life cycle. In this study, we combined high‐content screening (HCS) with the SARS‐CoV‐2 trVLP cell culture system, providing a powerful phenotype‐oriented approach to assess the antiviral potential of compounds on a large scale. We screened a library of 3,200 natural compounds and identified drupacine as a potential candidate against SARS‐CoV‐2 infection. Furthermore, we utilized a SARS‐CoV‐2 replicon system to demonstrate that drupacine could inhibit viral genome transcription and replication. However, in vitro, enzymatic assays revealed that the inhibition could not be attributed to conventional antiviral targets, such as the viral non‐structural proteins nsp5 (MPro) or nsp12 (RdRp). In conclusion, our findings position drupacine as a promising antiviral candidate against SARS‐CoV‐2, providing a novel scaffold for developing anti‐coronavirus disease 2019 therapeutics. Further investigation is required to pinpoint its precise target and mechanism of action.

In order to clarify the pre‐exist immunity background of different human coronaviruses (HCoV), this study investigated the positive rate of spike (S) protein antibodies of HCoV, including HCoV‐severe acute respiratory syndrome (SARS) −associated coronavirus (SARS‐CoV‐1), severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), Middle East respiratory syndrome coronavirus (MERS‐CoV), HCoV‐229E, HCoV‐NL63, HCoV‐HKU1 and HCoV‐OC43, before and after the Coronavirus Disease 2019 (COVID‐19) outbreak. We utilized pseudotyped virus‐based neutralization assays (PBNA) or enzyme‐linked immunosorbent assays (ELISA) to detect antibody levels against HCoV in serum samples collected in 2009–2010 and 2023. The PBNA results showed that neutralizing antibodies against SARS‐CoV‐1 and the MERS‐CoV were negative. In the serum samples from 2009 to 2010, neutralizing antibodies against SARS‐CoV‐2 (D614G) were negative, whereas in the serum samples from 2023, 73 samples (73 %) showed neutralizing reactions with the SARS‐CoV‐2 D614G strain, 96 samples (96 %) with the BA.5 strain, and 91 samples (91 %) with the BF.7 strain. Among pre‐COVID‐19 samples, 33 % (33/100) showed neutralizing reactions with HCoV‐229E and 63 % (63/100) with HCoV‐NL63. Among post‐COVID‐19 samples, 50 % (50/100) showed neutralizing reactions with HCoV‐229E and 49 % (49/100) with HCoV‐NL63. Due to the different receptors of alpha coronavirus genus compared to other beta coronavirus genus, neutralizing antibodies against HCoV‐OC43 and HCoV‐HKU1 virus cannot be detected by constructing corresponding pseudotyped virus. Binding antibodies against HCoV‐OC43 and HCoV‐HKU1 virus were detected using ELISA. The results revealed that among pre‐COVID‐19 samples, 83 % (83/100) and 45 % (45/100) had binding activity with HCoV‐OC43 and HCoV‐HKU1, respectively. Among post‐COVID‐19 samples, 100 % (100/100) and 81 % (81/100) had binding activity with HCoV‐OC43 and HCoV‐HKU1, respectively.

The vaccinia virus Tiantan (VTT) is widely utilized as a smallpox vaccine in China and holds significant importance in the prevention of diseases stemming from poxvirus infections. Nevertheless, few studies have investigated the influence of VTT infection on host gene expression. In this study, we constructed time series transcriptomic profiles of HeLa cells infected with both VTT and western reserve (WR) strains. We observed similar patterns of viral gene expression, while the expression levels of host genes varied between the two strains. There was an immediate and significant repression of host gene expression, particularly in genes associated with oxidative phosphorylation. Conversely, genes involved in nerve growth factor (NGF)‐stimulated transcription were significantly activated. The upregulation of genes linked to the ribonucleic acid (RNA)‐induced silencing complex (RISC) suggested a potential role for posttranscriptional regulation in the interaction between the vaccinia virus and the host. In the later stages of infection, pathways such as extracellular matrix organization, neutrophil degranulation, complement and interferon responses, translation, and programmed cell death are largely inhibited. A significant number of host genes exhibit correlations with changes in the expression levels of viral genes. The host genes that are negatively correlated with viral genes are mainly enriched in pathways associated with translation and the response to viral infection. This study significantly contributes to advancing our understanding of the dynamics between the vaccinia virus and the host, improving the application of VTTs and facilitating the development of effective vaccines against diseases such as smallpox and monkeypox.

Rhinovirus (RV) is a common pathogen that causes respiratory tract infection and can cause outbreaks in hospitals and welfare institutions. A cluster of respiratory diseases occurred in a primary school in Shenyang City, Liaoning Province, China, in 2022. In this outbreak, a total of 31 students had symptoms similar to those of upper respiratory tract infection, mainly cough and sore throat. Among them, 27 throat swabs were collected and identified for respiratory pathogens by TaqMan low‐density array (TLDA), quantitative real‐time polymerase chain reaction (PCR), reverse transcription‐nested PCR and whole‐genome sequencing. Out of the 27 specimens, 24 tested positive for RV, and 21 RV viral protein 1 sequences were obtained, of which 15 (71.43%) were identified as RV‐A49, while 2 RV‐A20 and 4 sequences from 2 specimens were RV‐A30 coinfected with RV‐C15. In addition, one whole‐genome sequence (WGS) of RV‐A49 was obtained, and three unique amino acid mutations were found compared to 23 WGS of RV‐A49 from GenBank. In conclusion, this outbreak of upper respiratory tract infection is caused by RV, mainly RV‐A49.

Chikungunya virus (CHIKV) infection, responsible for chikungunya fever and occasionally severe symptoms, has emerged as an increasing global health concern following several large‐scale outbreaks from Africa, Asia, Europe, and America. Over the past two decades, South and Southeast Asia regions have gradually become hot spots for outbreaks involving multiple CHIKV lineages. In China, most CHIKV infections are imported, making it crucial to trace the origins and transmission routes for effective prevention and control. In January 2024, a case of imported chikungunya fever was confirmed in Guangzhou City, Guangdong Province, China. However, the serum CHIKV viral concentration was too low for cultivation [reverse transcription‐polymerase chain reaction (RT‐PCR) detection, cycle threshold = 32.62]. Despite this, we successfully obtained the viral genome sequence directly from the whole blood sample using an optimized metatranscriptomic sequencing strategy, achieving a full‐length viral genome with an average depth of 54.3X. Further analysis confirmed that the CHIKV virus belonged to the Asian lineage, traced to Timor‐Leste, where an endemic CHIKV outbreak had been reported in January 2024, consistent with the patient’s travel history. Finally, we analyzed genetic evolutionary trends and amino acid site variations. This study highlights the identification of a CHIKV infection origin using direct whole‐blood metatranscriptomic sequencing, a valuable method for rapidly sequencing low viral‐load samples.