Search Results (4)

Hantaviruses are emerging pathogens with a worldwide distribution that can cause life-threatening diseases in humans. Monoclonal antibodies (MAbs) against hantavirus nucleocapsid (N) proteins are important tools in virus diagnostics, epidemiological studies and basic research studies on virus replication and pathogenesis. Here, we extend the collection of previously generated MAbs raised against a segment of Puumala orthohantavirus (PUUV) N protein harbored on virus-like particles (VLPs) and MAbs against N proteins of Sin Nombre orthohantavirus/Andes orthohantavirus by generating nine novel MAbs against N proteins of Dobrava-Belgrade orthohantavirus (DOBV), Tula orthohantavirus (TULV), Thottapalayam thottimvirus (TPMV) and PUUV. In order to have a wide collection of well-described hantavirus-specific MAbs, the cross-reactivity of novel and previously generated MAbs was determined against N proteins of 15 rodent- and shrew-borne hantaviruses by different immunological methods. We found that all MAbs, excluding TPMV-specific MAbs, demonstrated different cross-reactivity patterns with N proteins of hantaviruses and recognized native viral antigens in infected mammalian cells. This well-characterized collection of cross-reactive hantavirus-specific MAbs has a potential application in various fields of hantavirus research, diagnostics and therapy. Full article

Current vaccines against infectious diseases have primarily relied on attenuated or inactivated pathogens. However, self-assembled, virus-based nanoparticles (VNPs) are noninfectious multiprotein structures regarded as safe vaccine platforms for an efficient foreign antigen display within a host immune system. Currently, there is a low diversity of self-assembled, rod-shaped VNPs. Additionally, there is no information regarding the generation of tailed-bacteriophage nanotubes in yeast and their immunogenicity in mice. Here, we developed a novel tubular VNP-based vaccine platform utilizing a yeast-synthesized recombinant tail tube gp39 protein from bacteriophage vB_EcoS_NBD2 (NBD2). The diameter of these extremely flexible polytubes was ~12 nm, while the length varied from 0.1 µm to >3.95 µm. In this study, the immunogenicity of polytubes formed by the recombinant gp39 protein and the elicited antibody response were tested. The tubular structures formed by the recombinant gp39 protein were immunogenic in mice, although the addition of Freund’s adjuvant enhanced the anti-gp39 antibody response compared to the use of tubular structures alone. To further examine the applicability of novel polytubes as a carrier for foreign epitopes, the carboxy-terminal region within the gp39 protein was identified, allowing insertion of six histidine residues with no effect on the recombinant protein synthesis or structure self-assembly. This genetic insertion of a foreign epitope within the surface-exposed gp39 domains resulted in a repetitive display of the insert on the surface of NBD2 tail tube-originated polytubes. The combination of a repetitive, highly ordered display of foreign epitopes as well as tubular shape of nanoparticles can greatly enhance the immune response. Although more studies are needed, the flexible and extremely long polytubes formed by the recombinant tail tube gp39 protein represent a new potential platform for presenting target sequences on the exterior surface of the nanotubes. Full article

Nucleotides, peptides and proteins serve as a scaffold material for self-assembling nanostructures. In this study, the production of siphovirus vB_EcoS_NBD2 (NBD2) recombinant tail tube protein gp39 reached approximately 33% and 27% of the total cell protein level in Escherichia coli and Saccharomyces cerevisiae expression systems, respectively. A simple purification protocol allowed us to produce a recombinant gp39 protein with 85%–90% purity. The yield of gp39 was 2.9 ± 0.36 mg/g of wet E. coli cells and 0.85 ± 0.33 mg/g for S. cerevisiae cells. The recombinant gp39 self-assembled into well-ordered tubular structures (polytubes) in vivo in the absence of other phage proteins. The diameter of these structures was the same as the diameter of the tail of phage NBD2 (~12 nm). The length of these structures varied from 0.1 µm to >3.95 µm, which is 23-fold the normal NBD2 tail length. Stability analysis demonstrated that the polytubes could withstand various chemical and physical conditions. These polytubes show the potential to be used as a nanomaterial in various fields of science. Full article

The prevalence of allergic diseases is increasing in Lithuania as in the world. The prevalence of allergic sensitization is often higher than 50% of the population. The “hygiene hypothesis” proposed that reduced immune-stimulation by infections may have resulted in the more widespread clinical expression of atopic disease. However, it alone does not provide an adequate explanation for the observed increase of allergic diseases. Human rhinovirus infections are the major infections with a worldwide distribution. Viral infections of the respiratory tract are the most common triggers of acute asthma exacerbations. These exacerbations are poorly responsive to current asthma therapies and new approaches to therapy are needed. The aim of this review is to present the current knowledge and clinical implications of human rhinovirus infection in allergy and asthma development and needs for further research. Recent evidence has shown that the immune responses to human rhinoviruses differ between asthmatic and nonasthmatic subjects. Novel insights into the mechanisms of virus-induced asthma exacerbations support the possibility that viral infections may be involved in the epithelial cells damage, inflammation, and airway hyperresponsiveness as well as in profibrotic response and induction of airway remodeling. The data of original investigations support the concept that the immune stimulation by rhinovirus infections contributes to the development of asthma, when an atopic host is infected with human rhinoviruses. Early rhinoviral wheezing is the predictor of subsequent asthma development in high-risk children. Synergistic effect of allergic sensitization, allergen exposure, and viral infection was suggested in the increased risk of hospitalization for asthma in both children and adults. Timing of allergen exposure may be important in a synergistic outcome. The increased susceptibility to rhinovirus infections was identified in atopic asthma. This review also presents the current options on the treatment and prevention of virus-induced asthma. Further studies are needed in order to differentiate between the response to viruses of healthy and atopic or nonatopic asthmatic children and adults. New research data may lead to novel strategies in treatment and prevention of asthma exacerbations as well as prevention of asthma induction Full article