Volume 05 · Issue 05 · 2023

The monkeypox (mpox) virus has caused worldwide transmission since its initial report in England in early May 2022. Available data from the World Health Organization (WHO) show that Europe and the Americas experienced a huge wave of mpox virus infection. Now the number of infected cases is on the rise in Asia. Several sporadic infections have been reported in China. In this study, we obtained high‐quality whole viral genomic sequences using a mpox virus‐specific amplicon‐based sequencing strategy. Our analysis of the phylogenomic characteristics indicated that all eight mpox virus sequences from Guangzhou belonged to the clade IIb lineage B.1.3 cluster. However, we could not locate the exact origins where the virus was imported, based on all the available mpox virus sequences from the Global Initiative on Sharing Avian Influenza Data (GISAID) database (https://gisaid.org/), except for their closest sequence similarity to that was reported from Japan. Novel amino acid mutations were found among the eight cases, suggesting that a local transmission may have occurred in Guangzhou, China.

Data on the viral rebound and safety of nirmatrelvir/ritonavir in lung transplant (LTx) recipients are limited. The study prospectively followed four LTx recipients. Clinical characteristics, viral RNA dynamic in throat swabs, and tacrolimus blood concentration were monitored regularly. All four LTx recipients, aged 35–74 years, were not vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). They got coronavirus disease 2019 (COVID‐19) after more than one week of admission during the era of Omicron. All cases received nirmatrelvir/ritonavir (NM/r) within two days of infection, and the relative viral RNA copies dropped quickly. Viral load rebound was observed in all four cases after discontinuation of the first five days of NM/r treatment. Three of them received another 5‐days antiviral therapy with NM/r. The duration of positive viral PCR testing was 25‐28 days. None of them progressed into severe or critical COVID‐19. Tacrolimus was stopped 12 h before NM/r and held during the 5‐day course of antiviral therapy. Blood concentration of tacrolimus were maintained at a baseline level during these five days. Tacrolimus was re‐initiated at its baseline daily dose 3‐4 days after NM/r therapy. However, during the second round of antiviral therapy with NM/r, the concentration of tacrolimus fluctuated wildly. In conclusion, the 5‐day course of NM/r treatment was not sufficient for LTx recipients and the viral rebound was common. More data are needed to clarify whether LTx recipients with SARS‐CoV‐2 viral rebound could benefit from additional treatment with NM/r.

This paper comprehensively analyses the first‐ever monkeypox outbreak in Shenzhen, China, encompassing clinical symptomatology, therapeutic approaches, epidemiological research, and comprehensive laboratory tests, aiming to establish a robust reference for future monkeypox mitigation and management strategies. The investigation involved a thorough investigation of all identified positive cases, including extensive molecular analysis by nucleic acid detection and whole‐genome sequencing of the monkeypox virus. Contact tracing and containment of the infected individuals were also undertaken. Three distinct monkeypox cases were identified in this unique outbreak, exhibiting mild and atypical clinical manifestations, primarily fever and rash. All cases were associated with a single transmission chain, primarily facilitated through close contact and homosexual behavior, indicative of a high‐risk factor for monkeypox transmission. HIGHLIGHTS Scientific question A trend that has emerged in monkeypox outbreaks since 2022 has been a marked change in the transmission pattern of the monkeypox virus (MPXV). This paper comprehensively analyzes the first-ever monkeypox outbreak in Shenzhen, China, including clinical symptomatology, therapeutic approaches, epidemiologic investigation, and comprehensive laboratory testing. Evidence before this study The 2022 outbreak was primarily associated with close intimate contact (including sexual activity), and most cases were diagnosed in men who have sex with men, who often present with novel epidemiologic and clinical features. However, there is no published research related to the local monkeypox outbreak in mainland China. New findings As the first local outbreak of monkeypox, it was suspected that it had been spreading stealthily in Shenzhen for some time. All cases exhibited mild and atypical fever and rash, and were primarily facilitated through close contact and homosexual behavior. MPXV was detected in nasopharyngeal/oropharyngeal/anal swabs and blister fluid of these cases, and all of them are highly homologous to strains collected from Japan in 2023. Significance of the study This paper reports the first local outbreak of monkeypox in Shenzhen City, China, indicating that it is essential to enhance monkeypox surveillance and epidemic information reporting, increase public awareness and training for critical demographic and medical staff, and employ appropriate investigation methods and techniques for epidemiological investigations.

Infection with the Hantaan virus (HTNV) may result in severe hemorrhagic fever with renal syndrome (HFRS). The functions of HLA‐E‐restricted CD8+ T lymphocytes in virus control and vaccine development have recently received increased attention. The purpose of this research is to discover HLA‐E‐restricted CD8+ T cell epitopes on HTNV as well as the features of these epitope‐specific CD8+ T cells in HFRS patients. To anticipate HLA‐E‐restricted HTNV epitopes, the NetMHCpan servers were utilized. The K562/HLA‐E cell binding test and the enzyme‐linked immunospot assay were used to confirm epitope binding to HLA‐E. The number and features of HLA‐E‐restricted epitope‐specific CD8+ T lymphocytes in HFRS patients were investigated using tetramer staining, intracellular cytokine labeling, proliferation, and cytotoxicity assays. Six HTNV‐derived HLA‐E‐restricted CD8+ T cell epitopes were found in this study. In mild/moderate HFRS patients, the frequency of HLA‐E‐restricted epitope‐specific CD8+ T cells was greater than in severe/critical patients. CD38+HLA‐DR+ HLA‐E‐restricted CD8+ T cells were identified. Meanwhile, CD45RA+CCR7− effector memory‐re‐expressing CD45RA T cells with early and intermediate maturation and differentiation characteristics predominated. Notably, CD8+ T cells from milder HFRS patients produced more interferon‐γ, interleukin‐2, and granzyme B, had a stronger proliferative potential, and were inversely linked with the amount of plasma HTNV virus load. Furthermore, HLA‐E‐restricted epitope‐specific CD8+ T cells demonstrated improved cytotoxic activity in vitro during the acute stage of HFRS. Taken together, the findings demonstrate the protective effects of HLA‐E‐restricted CD8+ T cells during HTNV infection, suggesting that HLA‐E‐targeted vaccines against HTNV might be developed for HLA‐diverse populations. HIGHLIGHTS Scientific question Hantaan virus (HTNV) infection can cause severe hemorrhagic fever with renal syndrome (HFRS) and poses a global health and security threat due to its high mortality rate and ease of transmission as a bioweapon. Inactivated vaccines against HTNV have shown incomplete protective effects on the progression of HFRS, highlighting the urgent need for more effective HTNV vaccines. Evidence before this study HLA-E molecules consist of two different isoforms, HLA-E*0101 and HLA-E*0103, which collectively account for over 99% of their frequency. HLA-E molecules have the ability to bind to pathogen-derived nonapeptides, enabling the recognition of CD8+ T cells and triggering a wide range of responses against pathogens. This property suggests the potential for the broad application of peptide vaccines. New findings This study identified HLA-E-restricted HTNV CD8+ T cell epitopes that can induce specific CD8+ T cell responses. Importantly, CD8+ T cells restricted by HLA-E, observed in milder HFRS patients, exhibited enhanced capabilities in producing IFN-, interleukin-2, and granzyme B, along with increased proliferation. These CD8+ T cells also exhibited an activating phenotype characterized by CD38+HLA-DR+ expression and demonstrated cytotoxicity. These findings suggest the protective effects of HLA-E-restricted CD8+ T cell responses during HTNV infection. Significance of the study This study not only identified HLA-E-restricted CD8+ T cell epitopes specific to HTNV but also elucidated the characteristics and protective roles of these epitope-specific CD8+ T cells in HFRS patients. These findings have implications for advancing the design of safe and effective HTNV peptide vaccines, particularly in HLA-diverse populations.

West Nile virus (WNV) is a mosquito‐transmitted flavivirus distributed globally for decades and can cause disease in humans and animals. So far, no WNV vaccine has been licensed for human use. Therefore, the development of novel candidate vaccines and the improvement of vaccination strategies is imperative. As the WNV envelope (E) glycoprotein plays an important role in mediating viral binding to cellular receptors and virus‐cell membrane fusion, it is a critical target for the host humoral response. Here, we prepared a recombinant truncated envelope protein of WNV (rWNV‐80E) and developed a WNV subunit vaccine formulation with a combination of aluminum hydroxide (alum) and a synthetic oligonucleotide CpG as adjuvants. C57BL/6 mice were immunized twice intramuscularly at 28‐day intervals with 5 µg purified rWNV‐80E adjuvanted with Alum/CpG. WNV E‐specific IgG was detected by enzyme‐linked immunosorbent assay and neutralizing antibodies (nAbs) was detected using single‐round infectious particles of WNV. Furthermore, T cell immunity was detected by enzyme‐linked immunospot assay and intracellular cytokine staining assay. Notably, rWNV‐80E was highly immunogenic and elicited potent humoral and cell immunity, as evidenced by significant levels of IFN‐γ and TNF‐α secretion in the T cells of mice. In summary, the Alum/CpG‐adjuvanted rWNV‐80E subunit vaccine elicited potent and balanced B‐ and T‐cell immunity in mice, and therefore it is a promising candidate vaccine that warrants further investigation for use in human or veterinary applications. HIGHLIGHTS Scientific question Although several novel West Nile virus (WNV) vaccines have been developed, none of the vaccines has been licensed for human use. Novel WNV candidate vaccines induced both humoral and cellular immunity is imperative. Evidence before this study The envelope protein of WNV is an important vaccine target. The protection conferred by WNV E subunit vaccines in mice has been described in previous reports. The appropriate adjuvant is an effective means to improve the WNV E subunit vaccine immunity. New findings We prepared a soluble recombinant truncated envelope protein of WNV based on the XJ11129 strain in a eukaryotic expression platform and developed a candidate vaccine formulation with Alum/CpG as adjuvants. The immunization results showed that Alum/CpG adjuvanted rWNV-80E vaccine not only elicited high and sustained titers of serum IgG and nAb but also significant levels of IFN-γ and TNF-α secretion of CD8+ T cells in mice. Significance of the study The recombinant truncated envelope protein of WNV adjuvanted with Alum/CpG induces potent humoral and T cell immunity in mice, providing a promising vaccine candidate for further investigation for human or veterinary applications.

Although inactivated vaccines against rabies have the advantage of high safety, effective protection against rabies virus (RABV) infection often requires multiple, high‐dose immunization. Incorporating a molecular adjuvant into the viral particles has been found to be a useful strategy to promote the immune effectiveness of inactivated vaccines. In this study, we constructed a recombinant virus, rCVS11‐LTB, which chimerically expresses a molecular adjuvant heat‐labile enterotoxin B subunit (LTB) protein on the surface of the RABV particles. Immunogenicity in vivo was found to be promoted by rCVS11‐LTB through the activation of dendritic cells (DCs). Our results demonstrated that inactivated rCVS11‐LTB was able to induce higher levels of virus‐neutralizing antibodies (VNAs) in both mice and dogs than the parent virus rCVS11, to enhance the cellular immune response and T cell immune memory in mice, and was also able to provide 100% protection in mice from lethal doses of rabies virus, indicating its potential as a safe and effective inactivated rabies vaccine candidate. HIGHLIGHTS Scientific question To reduce and eliminate the rabies epidemic, it is essential to improve the effectiveness of the rabies vaccine. Evidence before this study Many studies have demonstrated that adjuvants, particularly molecular adjuvants targeting the immune cells, play an important role in improving the immune efficacy of inactivated vaccines. Escherichia coli heat-labile enterotoxin B subunit (LTB) shows advantages in promoting the immune efficacy of vaccines by activating the dendritic cells. New findings A recombinant virus rCVS11-LTB was constructed in this study, which could display the LTB protein on the surface of viral particles. Inactivated rCVS11-LTB was able to induce the higher levels of virus-neutralizing antibodies (VNAs) in both mice and dogs, and to induce faster and stronger cellular immune responses and the production of CD4+ CTM in mice than rCVS11 post immunization. In addition, two doses of inactivated rCVS11-LTB could completely protect the mice from the challenge with a lethal dose of rabies virus. Significance of the study The recombinant virus rCVS11-LTB chimeric-expressing the molecular adjuvant LTB can induce high levels of humoral and cellular immune responses in vivo and provide 100% protection against RABV challenge in mice, demonstrating its potential as an effective inactivated rabies vaccine candidate.

The coronavirus disease 2019 (COVID‐19) pandemic is the third human disease outbreak caused by an emerging coronavirus in the 21st century. Caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the COVID‐19 pandemic has been the most devastating, with millions of deaths. Medical countermeasures are needed to limit the number of infections and fatalities. Here, we discuss advances in clinical and research‐based treatment methods for SARS‐CoV‐2 that were initially derived from treatments for other coronaviruses. Recent advances in SARS‐CoV‐2 treatments, from traditional drugs and immunotherapies to artificial intelligence to predict potential future treatment methods, are summarized and discussed.

During severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, activated macrophages, dendritic cells (D.C.), neutrophils, and natural killer (N.K.) cells are the first defense against infection. These immune effectors trap and ingest the virus, kill infected epithelial cells, or produce anti‐viral cytokines. Evidence suggests that aging, obesity, and mental illness can lead to weakened innate immunity and, thus, are all associated with elevated infection and severe disease progression of coronavirus disease 2019 (COVID‐19). Innate immune defense networks play a fundamental role in suppressing viral replication, infection establishment, and viral pathogenesis of SARS‐CoV‐2 and other respiratory viruses.