Viral immunology最新文献

La Crosse virus (LACV), a constituent of the California serogroup (CSG) within the genus Orthobunyavirus in the Peribunyaviridae family, is the causative agent of LACV encephalitis. This form of encephalitis stands as one of the most significant and burgeoning mosquito-borne diseases in the United States, ranking as the second most prevalent mosquito-borne illness following West Nile virus encephalitis. Predominantly identified in the Midwestern, Mid-Atlantic, and Southeastern regions of the United States, LACV primarily afflicts humans through the bites of Aedes triseriatus mosquitoes. Its genome, divided into three segments, encodes proteins that not only facilitate efficient replication within hosts but also hinder host immune responses. Infections by LACV can lead to a spectrum of neurological outcomes, ranging from mild aseptic meningitis to severe encephalitis with the potential for long-lasting neurological deficits. Despite the availability of diagnostic tools, several challenges persist. Currently, the management of LACV infection remains supportive, underscoring the importance of preventative measures in substantially mitigating the infection's incidence and severity. Moreover, global warming elevates the risk of LACV spreading to new territories. This review delves into recent advancements concerning the transmission and pathogenesis of LACV, drawing upon current knowledge regarding its genetic framework, transmission modes, geographical spread, phylogenetic relationships, clinical presentations and neuropathogenic effects, diagnostic approaches, treatment modalities, and prevention strategies.

Tick-borne viruses are an increasing global health concern due to their significant impact on humans and animals, as well as their expanding geographic distribution. Notable viruses in this group include the tick-borne encephalitis virus (TBEV), Crimean-Congo hemorrhagic fever virus (CCHFV), Heartland virus (HRTV), and Powassan virus (POWV). This review evaluates their geographic spread, clinical effects, diagnostic challenges, treatment options, and research gaps. These viruses are increasingly spreading due to climate change and shifting tick habitats. The TBEV is moving into new areas of Europe and Asia, while the CCHFV is advancing into the Balkans and Caucasus. The HRTV has become more common in the United States, and the POWV is emerging in new regions of North America. Symptoms can vary from mild fever to severe neurological and hemorrhagic conditions. Diagnostic difficulties stem from inconsistent test accuracy, and treatment options are scarce, with only a few vaccines available. Tick-borne viruses represent a significant and expanding health threat, given their diverse clinical outcomes and diagnostic difficulties. Developing more accurate and accessible diagnostic tools is critical for early identification and treatment. Additionally, creating effective vaccines will be essential to reducing the overall burden of these viruses. With the increasing spread of tick-borne viruses, enhanced surveillance, ongoing research efforts, and strategic public health interventions are necessary to effectively control their impact and prevent further outbreaks.

Evaluating the impact of cardiac surgery on humoral and cellular immunity in pediatric congenital heart disease patients with prior Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection or vaccination is crucial for postoperative care planning. This study enrolled 61 pediatric patients undergoing cardiac surgery with cardiopulmonary bypass at a single institution. Measurements were taken before the operation, immediately postoperation, and during the first follow-up examination at least 1 month later. The evaluations included SARS-CoV-2-specific immunoglobulin G (IgG) and neutralizing antibodies for humoral immunity assessment, as well as specific and nonspecific T-cell immune responses to gauge T-cellular immunity and functionality. The results demonstrated that the serum titers of IgG and neutralizing antibodies remained comparable postsurgery to preoperative levels. Nevertheless, significant decreases in specific and nonspecific T-cell immune responses, along with a decline in CD3⁺ T-cell numbers, were observed immediately following surgery. This was followed by a gradual recovery of immune response to preoperative levels approximately 1 month later. These findings suggest that in the first month following cardiac surgery in pediatric patients, residual specific antibodies, potentially derived from the original production or plasma transfusion, may provide partial protection against COVID-19 infection. Subsequently, T-cellular immunity gradually recovers and resumes its protective role. The study provides important insights into the dynamics of immune recovery following cardiac surgery in this vulnerable patient population, which may be essential for optimizing postoperative management and reducing the risk of COVID-19 infection.

Respiratory syncytial virus (RSV) is a significant cause of disease in the young and old. Recently, pre-fusion F protein vaccines for RSV have received food and drug administration (FDA) approval to protect adults aged 60 years and older; however, vaccines evaluated against RSV typically do not elicit complete or durable protective immunity. We previously showed that an RSV G protein central conserved domain (CCD) nanoparticle vaccine containing an S177Q mutation (NP-S177Q) induced favorable immunogenicity and RSV-neutralizing antibodies compared with RSV G protein vaccination alone in mice. Boosting BALB/c mice with NP-S177Q vaccines improved correlates of protection and reduced markers of immunopathology following RSV challenge. This study examined microparticle (MP) vaccines displaying the CCD with an RSV G S177Q mutation (MP-S177Q) adjuvanted with monophosphoryl lipid A (MPLA) in BALB/c mice. Our findings show that mice adjuvanted MP-S177Q vaccination develop effective viral neutralization compared with MP-WT and MP-S177Q vaccination and have improved bronchoalveolar Th1-type cytokine responses following the RSV challenge compared with MP-WT or vehicle-vaccinated mice. This study shows that a rationally mutated RSV G protein MP vaccine is safe, effective, and can advance precision RSV vaccines.

Interleukin-35 (IL-35) has an immunosuppressive function through the regulation of immune cells during infectious diseases, autoimmune disorders, and cancers. The modulatory role of IL-35 in T lymphocytes, which are involved in host immune responses during human immunodeficiency virus-1 (HIV-1) infection, has not been elucidated. The aim of the current study was to investigate the role of regulatory function of IL-35 to T-cell activity in patients living with chronic HIV-1 infection. Sixty-seven patients living with chronic HIV-1 infection and 17 controls were enrolled in the study. IL-35 levels were measured via an enzyme-linked immunosorbent assay. Purified CD4⁺ and CD8⁺ T cells were stimulated with recombinant human IL-35. The secretion of cytokines and cytotoxic molecules, the mRNA levels of IL-35 receptor subunits and transcription factors, the expression of immune checkpoint molecules, and cell proliferation were assessed to evaluate the effect of IL-35 on T lymphocyte function in vitro. Compared with controls, patients living with chronic HIV-1 infection presented increased plasma IL-35 levels. IL-35 stimulation did not affect either the expression of IL-35 receptor subunits or the proliferation of CD4⁺ and CD8⁺ T cells from either patients living with chronic HIV-1 infection or controls. IL-35 stimulation downregulated transcription factor mRNA expression and cytokine secretion by CD4⁺ T cells as well as cytotoxic molecule production by CD8⁺ T cells from both patients living with chronic HIV-1 infection and controls. This process was accompanied by increased expression of immune checkpoint molecules on CD4⁺ and CD8⁺ T cells. The addition of IL-35 also reduced perforin and granzyme B secretion by HIV-1-specific CD8⁺ T cells from patients living with chronic HIV-1 infection. Increased plasma IL-35 in patients living with chronic HIV-1 infection might dampen the activation of CD4⁺ and CD8⁺ T cells, leading to T-cell exhaustion.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, has been spreading and changing globally. Adjuvant-based vaccines can improve vaccine protection by enhancing the immune response. Bacterial flagellin is a potent adjuvant and promotes protective immune responses. Here, we successfully expressed and purified the S1 subunit of SARS-CoV-2. The adjuvanticity of flagellin (FliC) of Salmonella Typhimurium in mice was determined by combining it with the recombinant S1 subunit vaccine. FliC-adjuvanted S1 vaccine could induce significantly enhanced S1-specific Immunoglobulin G (IgG), IgG1 and IgG2a titers, SARS-CoV-2-neutralizing antibodies, and levels of Th1 type (TNF-α and IFN-γ) and Th2 type (Interleukin-5 (IL-5), IL-4, IL-10, and IL-13) cytokines in splenocytes compared with the S1 alone group. Additionally, the titers of S1-specific IgG antibodies in the FliC adjuvant group could maintain a high level for at least 2 months. These results indicated that the FliC-adjuvanted S1 subunit vaccine could trigger strong humoral and cellular immune responses, which could promote the ongoing development of COVID-19 vaccines.

The Heartland virus (HRTV) is a tick-borne human pathogenic phlebovirus that primarily causes leukopenia and thrombocytopenia. It is transmitted by Amblyomma americanum type of tick, that is, notable for their aggressive biting behavior, affinity for human hosts, and high prevalence. Developing vaccines or immunizations against HRTV is gaining importance as a public-health preventive strategy. The current study was planned to prioritize a multi-epitope stable mRNA vaccine model against HRTV from lead B-cell and T-cell epitopes (with IC₅₀ < 100 nM) of HRTV proteome following advanced immunoinformatics approaches. Model constructs were designed by linking the most potent, nonallergenic epitopes along with incorporation of human ribosomal protein adjuvant for immune response enhancement. The immunogenic potential of the coding vaccine molecule was examined via molecular docking against toll-like receptors immune receptors followed by normal mode analysis and molecular dynamics simulations-based energy minimization, molecular stability, and flexibility assessments. A robust, stable circular mRNA precursor of multi-epitopes vaccine model was designed by incorporating the Kozak consensus sequence, a start codon, and essential elements such as MHC class I trafficking domain (MITD), tPA, Goblin 5' and 3' Untranslated Region (UTRs), and a poly (A) tail. This strategic amalgamation ensures elevated immunogenicity and predicts a promising circular mRNA vaccine model against HRTV. The immune simulation predicted that the designed model vaccine is capable to elicit cell-mediated and humoral immune responses. The predicted circular mRNA vaccine precursor model is promising against HRTV to examine experimentally for its immunogenicity and safety features.

Dengue fever (DF) is a common mosquito-borne viral infection caused by any of the four dengue virus (DENV) serotypes. In recent years, the global incidence of DF has risen rapidly, which has widely threatened the health of millions of people in the United States, Southeast Asia, and the Western Pacific. The challenges for the prevention and control of DENV infection have become increasingly severe. Over the years, advances in the area of DF research have been continuously updating. In this review, we provide an updated and more in-depth overview of dengue epidemiology and pathogenesis, along with recent progress in diagnostic approaches (including methods to address cross-reactivity with other flaviviruses) and an expanded discussion of current dengue vaccine development, such as CYD-TDV (Dengvaxia), TV003/TV005, and the new TAK-003. This comprehensive perspective aims to offer references for the prevention, clinical diagnosis, and control of the disease.