The PreS-Based Recombinant Vaccine VVX001 Induces Hepatitis B Virus Neutralizing Antibodies in a Low-Responder to HBsAg-Based HBV Vaccines.

Approximately 10-20% of subjects vaccinated with HBsAg-based hepatitis B virus (HBV) vaccines are non-responders. BM32 is a recombinant grass pollen allergy vaccine containing the HBV-derived preS surface antigen as an immunological carrier protein. PreS includes the binding site of HBV to its receptor on hepatocytes.

The cytoskeletal protein profilin is an important allergen in saltwort ().

Pollen from , i.e., saltwort, Russian thistle, is a major allergen source in the coastal regions of southern Europe, in Turkey, Central Asia, and Iran.

Trimeric Bet v 1-specific nanobodies cause strong suppression of IgE binding.

Background: Around 20% of the population in Northern and Central Europe is affected by birch pollen allergy, with the major birch pollen allergen Bet v 1 as the main elicitor of allergic reactions. Together with its cross-reactive allergens from related trees and foods, Bet v 1 causes an impaired quality of life. Hence, new treatment strategies were elaborated, demonstrating the effectiveness of blocking IgG antibodies on Bet v 1-induced IgE-mediated reactions.

Vaccine Based on Recombinant Fusion Protein Combining Hepatitis B Virus PreS with SARS-CoV-2 Wild-Type- and Omicron-Derived Receptor Binding Domain Strongly Induces Omicron-Neutralizing Antibodies in a Murine Model.

Background: COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a recurrent endemic disease affecting the whole world. Since November 2021, Omicron and its subvariants have dominated in the spread of the disease. In order to prevent severe courses of disease, vaccines are needed to boost and maintain antibody levels capable of neutralizing Omicron.

Coupling of a Major Allergen to the Surface of Immune Cells for Use in Prophylactic Cell Therapy for the Prevention of IgE-Mediated Allergy.

Up to a third of the world's population suffers from allergies, yet the effectiveness of available preventative measures remains, at large, poor. Consequently, the development of successful prophylactic strategies for the induction of tolerance against allergens is crucial. In proof-of-concept studies, our laboratory has previously shown that the transfer of autologous hematopoietic stem cells (HSC) or autologous B cells expressing a major grass pollen allergen, Phl p 5, induces robust tolerance in mice.

Albumins represent highly cross-reactive animal allergens.

Albumins from animals are highly cross-reactive allergens for patients suffering from immunoglobulin E (IgE)-mediated allergy. Approximately 20-30% of cat and dog allergic patients show IgE reactivity and mount IgE-mediated allergic reactions to cat and dog albumin. It is astonishing that allergic patients can develop specific IgE responses against animal albumins because these proteins exhibit a more than 70% sequence identity to human serum albumin (HSA) which is the most abundant protein in the blood of the human body.

Monomeric agonist peptide/MHCII complexes activate T-cells in an autonomous fashion.

Molecular crowding of agonist peptide/MHC class II complexes (pMHCIIs) with structurally similar, yet per se non-stimulatory endogenous pMHCIIs is postulated to sensitize T-cells for the recognition of single antigens on the surface of dendritic cells and B-cells. When testing this premise with the use of advanced live cell microscopy, we observe pMHCIIs as monomeric, randomly distributed entities diffusing rapidly after entering the APC surface. Synaptic TCR engagement of highly abundant endogenous pMHCIIs is low or non-existent and affects neither TCR engagement of rare agonist pMHCII in early and advanced synapses nor agonist-induced TCR-proximal signaling.

Natural human Bet v 1-specific IgG antibodies recognize non-conformational epitopes whereas IgE reacts with conformational epitopes.

Background: The nature of epitopes on Bet v 1 recognized by natural IgG antibodies of birch pollen allergic patients and birch pollen-exposed but non-sensitized subjects has not been studied in detail.

Objective: To investigate IgE and IgG recognition of Bet v 1 and to study the effects of natural Bet v 1-specific IgG antibodies on IgE recognition of Bet v 1 and Bet v 1-induced basophil activation.

Methods: Sera from birch pollen allergic patients (BPA, n = 76), allergic patients without birch pollen allergy (NBPA, n = 40) and non-allergic individuals (NA, n = 48) were tested for IgE, IgG as well as IgG and IgG reactivity to folded recombinant Bet v 1, two unfolded recombinant Bet v 1 fragments comprising the N-terminal (F1) and C-terminal half of Bet v 1 (F2) and unfolded peptides spanning the corresponding sequences of Bet v 1 and the apple allergen Mal d 1 by ELISA or micro-array analysis.

Nasal IL-13 production identifies patients with late-phase allergic responses.

Background: There is limited knowledge on how local cytokine secretion patterns after nasal allergen challenge correlate with clinical symptoms especially with regard to the "late allergic response," which occurs in approximately 40% to 50% of patients with allergy.

Objective: We sought to characterize the immunologic and clinical nasal responses to birch pollen allergen challenge with a special focus on the late allergic response.

Methods: In this randomized, double-blind, placebo-controlled trial, birch pollen-allergic participants were challenged with birch pollen extract (n = 20) or placebo (n = 10) on 3 consecutive days.

Bos d 13, A Novel Heat-Stable Beef Allergen.

Scope: Red meat, a staple food of Western diets, can also induce IgE-mediated allergic reactions. Yet, apart from the heat-labile protein serum albumin and the carbohydrate α-Gal, the molecules causing allergic reactions to red meat remain unknown.

Methods And Results: IgE reactivity profiles of beef-sensitized individuals are analyzed by IgE-immunoblotting with protein extracts from raw and cooked beef.

Optimizing cultivation conditions for the highest expression of fungal allergens.

Background: Any reliable allergy diagnosis depends on the quality of the testing material. In the case of fungal allergy, fungal extracts, typically used as test solutions, exhibit considerable differences in their allergenicity. Better knowledge of fungal allergen expression would enable the production of diagnostic fungal extracts of higher quality and, thus, improve the specificity and sensitivity of fungal allergy diagnosis.

Expression and regulation of Siglec-6 (CD327) on human mast cells and basophils.

Background: Mast cells (MC) and basophils are effector cells of allergic reactions and display a number of activation-linked cell surface antigens. Of these antigens, however, only a few are functionally relevant and specifically expressed in these cells.

Objective: We sought to identify MC- and basophil-specific surface molecules and to study their cellular distribution and regulation during cytokine-induced and IgE-dependent activation.

Isolation of nanobodies with potential to reduce patients' IgE binding to Bet v 1.

Background: Recent studies showed that a single injection of human monoclonal allergen-specific IgG antibodies significantly reduced allergic symptoms in birch pollen-allergic patients. Since the production of full monoclonal antibodies in sufficient amounts is laborious and expensive, we sought to investigate if smaller recombinant allergen-specific antibody fragments, that is, nanobodies, have similar protective potential. For this purpose, nanobodies specific for Bet v 1, the major birch pollen allergen, were generated to evaluate their efficacy to inhibit IgE-mediated responses.

Preventive Administration of Non-Allergenic Bet v 1 Peptides Reduces Allergic Sensitization to Major Birch Pollen Allergen, Bet v 1.

IgE-mediated allergy to birch pollen affects more than 100 million patients world-wide. Bet v 1, a 17 kDa protein is the major allergen in birch pollen responsible for allergic rhinoconjunctivitis and asthma in birch pollen allergic patients. Allergen-specific immunotherapy (AIT) based on therapeutic administration of Bet v 1-containing vaccines is an effective treatment for birch pollen allergy but no allergen-specific forms of prevention are available.

From Allergen Molecules to Molecular Immunotherapy of Nut Allergy: A Hard Nut to Crack.

Peanuts and tree nuts are two of the most common elicitors of immunoglobulin E (IgE)-mediated food allergy. Nut allergy is frequently associated with systemic reactions and can lead to potentially life-threatening respiratory and circulatory symptoms. Furthermore, nut allergy usually persists throughout life.

The Molecular Allergen Recognition Profile in China as Basis for Allergen-Specific Immunotherapy.

Approximately 30% of the world population suffers from immunoglobulin-E (IgE)-mediated allergy. IgE-mediated allergy affects the respiratory tract, the skin and the gastrointestinal tract and may lead to life-threatening acute systemic manifestations such as anaphylactic shock. The symptoms of allergy are mediated by IgE-recognition of causative allergen molecules from different allergen sources.

Neutralization of SARS-CoV-2 requires antibodies against conformational receptor-binding domain epitopes.

Background: The determinants of successful humoral immune response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are of critical importance for the design of effective vaccines and the evaluation of the degree of protective immunity conferred by exposure to the virus. As novel variants emerge, understanding their likelihood of suppression by population antibody repertoires has become increasingly important.

Methods: In this study, we analyzed the SARS-CoV-2 polyclonal antibody response in a large population of clinically well-characterized patients after mild and severe COVID-19 using a panel of microarrayed structurally folded and unfolded SARS-CoV-2 proteins, as well as sequential peptides, spanning the surface spike protein (S) and the receptor-binding domain (RBD) of the virus.

IgE Epitopes of the House Dust Mite Allergen Der p 7 Are Mainly Discontinuous and Conformational.

Background: Several studies indicate that Der p 7 is an important and clinically relevant allergen of which should be included in vaccines for treatment of house dust mite (HDM) allergy. Aim of this study was to characterize the IgE epitopes of Der p 7.

Methods: Recombinant Der p 7 was expressed and purified, analyzed for fold by circular dichroism and tested for its allergenic activity by basophil activation.

Microarray Technology May Reveal the Contribution of Allergen Exposure and Rhinovirus Infections as Possible Triggers for Acute Wheezing Attacks in Preschool Children.

Allergen exposure and rhinovirus (RV) infections are common triggers of acute wheezing exacerbations in early childhood. The identification of such trigger factors is difficult but may have therapeutic implications. Increases of IgE and IgG in sera, were shown against allergens and the N-terminal portion of the VP1 proteins of RV species, respectively, several weeks after allergen exposure or RV infection.

Dissociation of the respiratory syncytial virus F protein-specific human IgG, IgA and IgM response.

Human respiratory syncytial virus (RSV) is one of the most important causes of severe respiratory tract infections in early childhood. The only prophylactic protection is the neutralizing antibody, palivizumab, which targets a conformational epitope of the RSV fusion (F) protein. The F protein is generated as a F0 precursor containing two furin cleavage sites allowing excision of the P27 fragment and then gives rise to a fusion-competent version consisting of the N-terminal F2 subunit and the a C-terminal F1 subunits linked by two disulphide bonds.

Quantification, epitope mapping and genotype cross-reactivity of hepatitis B preS-specific antibodies in subjects vaccinated with different dosage regimens of BM32.

Background: Chronic hepatitis B virus (HBV) infections are a global health problem. There is a need for therapeutic strategies blocking continuous infection of liver cells. The grass pollen allergy vaccine BM32 containing the preS domain of the large HBV surface protein (LHBs) as immunogenic carrier induced IgG antibodies in human subjects inhibiting HBV infection in vitro.

Features of the Human Antibody Response against the Respiratory Syncytial Virus Surface Glycoprotein G.

Respiratory syncytial virus (RSV) infections are a major cause of serious respiratory disease in infants. RSV occurs as two major subgroups A and B, which mainly differ regarding the surface glycoprotein G. The G protein is important for virus attachment and G-specific antibodies can protect against infection.