Viral immunology最新文献

The aim of this study was to compare immune response against SARS-CoV-2 in Balb/C mice when self-amplifying RNA lipid nanoparticles (saRNA LNPs) combined with TLR4 Agonist (monophosphoryl lipid A) as the adjuvant 1 and TLR9 Agonist (CpG) as the adjuvant 2. Here, we found that the size distribution of saRNA LNPs was 88-165 nm with a mean size of 126 nm. Although TLR4 Agonist (adjuvant 1) and TLR9 Agonist (adjuvant 2) could increase the expression of S-protein in HEK293T/17 cells compared with saRNA LNPs alone, the combination of both adjuvants had a significant effect on the expression of the S-protein. Moreover, combining TLR4 Agonist (adjuvant 1) and TLR9 Agonist (adjuvant 2) increased the antibody (IgG and IgA) titer. Here, the ratio of IgG2a/IgG1 showed a T helper type 1-biased response. ELISpot test showed the mice vaccinated with saRNA LNPs+ TLR4 Agonist and TLR9 Agonist had significantly more secreting cells compared with other vaccinated mice (p < 0.05). The secretion of interleukin (IL)-4 and interferons (IFN)-γ by re-stimulated splenocytes confirmed these data. Significant differences in concentration of IL-4 and IFN-γ produced by activated splenocytes were also seen in the mice vaccinated with saRNA LNPs+ TLR4 Agonist and microparticles compared with other groups (p < 0.05). The highest quantity of S-protein was detected in the blood, followed by the small intestine and spleen. The interesting thing was that no significant difference was seen between the amount of S-protein induced by different formulations and the type of adjuvant did not affect the biodistribution.

Analysis of the viral load in respiratory syncytial virus (RSV) infection has focused on the nasopharyngeal site (NPS) near the lower respiratory tract, which is the primary lesion site, and the viral load in the anterior nasal site (ANS) near the nostrils has not been clarified in adults or children. The study evaluated the nasal distribution of RSV. A total of 49 patients, with 0 months to 71 years of age, participated in the study. A total of 774 specimens were collected from the ANS and NPS. In the pediatric group, the highest viral load in the NPS was 1.1 × 10¹⁰ copies/mL on day 1 of onset, and the highest in the ANS was 4.1 × 10⁹ copies/mL on day 2. Thereafter, the viral load at both sites decreased gradually over time. The adult group showed a peak viral load on the onset day, with 1.5 × 10¹⁰ copies/mL in the NPS and 8.4 × 10⁹ copies/mL in the ANS. By day 7 of onset, the viral load was 3.9 × 10⁸ copies/mL in the NPS and 1.3 × 10⁸ copies/mL in the ANS, indicating that the viral load at both sites remained parallel. We demonstrated that the RSV load was present in the ANS and NPS of children and adults from the date of onset. The ANS is closer to the nostrils and is a more promising specimen collection site than the NPS at all ages but has a lower viral load than the NPS.

Human metapneumovirus (HMPV) is a prominent respiratory pathogen causing significant morbidity and mortality worldwide, mostly in young teenagers, the old, and immunocompromised individuals. Despite its clinical impact, no licensed vaccine is currently available, highlighting the urgent need for effective prophylactic strategies. This research aimed to design a multiepitope vaccine (MEV) targeting conserved and immunodominant regions of HMPV, leveraging immunoinformatics tools to ensure broad coverage and efficacy against the virus and its diverse sublineages. Glycoproteins from HMPV genotypes A2a, A2b, and A2c were analyzed to identify 18 highly antigenic and overlapping epitopes capable of eliciting robust B-cell, T-cell, and interferon-gamma (IFN-γ)-mediated immune responses. Toxicity and allergenicity studies confirmed the safety of particular epitopes, which were incorporated into two vaccine constructs using immunogenic linkers and adjuvants. The chimeric vaccines displayed high antigenicity, molecular stability, and nonallergenic properties. Structural refinement and Ramachandran plot analyses established the stability and accuracy of the 3D models. Molecular docking studies verified strong interactions with immune receptors, particularly toll-like receptor (TLR)2, TLR3, TLR4, TLR8, and human leukocyte antigen molecules, indicating robust immune stimulation potential. Molecular dynamics simulations further validated the vaccine's stability and interaction dynamics, with immune simulations predicting promising responses. The designed vaccine constructs were shown to be highly soluble, stable, and suitable for recombinant expression in Escherichia coli, enabling further biochemical and immunoreactivity validation. These findings provide a foundation for next-generation vaccine development against HMPV, offering promising avenues for clinical application and future research. [Figure: see text].

Varicella Zoster Virus (VZV), a member of the herpes virus family, causes varicella (chicken pox) upon primary infection and later manifests as herpes zoster ([HZ] or shingles) upon reactivation. VZV-specific T-cell immunity acquired during primary infection aids recovery, with the virus lying latent in neuronal ganglia until it transports to the skin axonally during reactivation. It has been well-established that reduced T-cell recognition and proliferation, as well as immunosuppression more generally, contribute to VZV reactivation. It has also been discovered that seasonal variation, which is linked to ultraviolet radiation (UVR), correlates with increased HZ cases. This correlation may be explained by the direct immunosuppressant effects of UVR, with melanin offering photoprotective effects that decrease reactivation rates. However, an underexplored aspect of this correlation is the potential role of the skin microbiome in UVR-induced VZV reactivation. Vital for skin homeostasis and immune modulation, the skin microbiome has been found to influence various skin conditions. Preliminary evidence suggests that microbiome diversity may influence VZV reactivation rates, supported by antibiotic-induced effects on HZ incidence. Research also indicates the microbiome's modulating effect on UVR-induced immune suppression, emphasizing its potential significance in VZV reactivation. The skin microbiome's contribution may also help further explain sex and ethnicity-specific variations in VZV reactivation rates. Understanding the interplay between UVR, the skin microbiome, and VZV reactivation warrants further investigation and may help uncover preventive strategies for mitigating VZV reactivation.

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.