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Background: SARS‐CoV‐2 has triggered a pandemic and contributes to long‐lasting morbidity. Several studies have investigated immediate cellular and humoral immune responses during acute infection. However, little is known about long‐term effects of COVID‐19 on the immune system. Methods: We performed a longitudinal investigation of cellular and humoral immune parameters in 106 non‐vaccinated subjects ten weeks (10 w) and ten months (10 m) after their first SARS‐CoV‐2 infection. Peripheral blood immune cells were analyzed by multiparametric flow cytometry, serum cytokines were examined by multiplex technology. Antibodies specific for the Spike protein (S), the receptor‐binding domain (RBD) and the nucleocapsid protein (NC) were determined. All parameters measured 10 w and 10 m after infection were compared with those of a matched, noninfected control group (n = 98). Results: Whole blood flow cytometric analyses revealed that 10 m after COVID‐19, convalescent patients compared to controls had reduced absolute granulocyte, monocyte, and lymphocyte counts, involving T, B, and NK cells, in particular CD3+CD45RA+CD62L+CD31+ recent thymic emigrant T cells and non‐class‐switched CD19+IgD+CD27+ memory B cells. Cellular changes were associated with a reversal from Th1‐ to Th2‐dominated serum cytokine patterns. Strong declines of NC‐ and S‐specific antibody levels were associated with younger age (by 10.3 years, p <.01) and fewer CD3−CD56+ NK and CD19+CD27+ B memory cells. Changes of T‐cell subsets at 10 m such as normalization of effector and Treg numbers, decline of RTE, and increase of central memory T cell numbers were independent of antibody decline pattern. Conclusions: COVID‐19 causes long‐term reduction of innate and adaptive immune cells which is associated with a Th2 serum cytokine profile. This may provide an immunological mechanism for long‐term sequelae after COVID‐19. [ABSTRACT FROM AUTHOR]

Background: IgE cross‐sensitization to major birch pollen allergen Bet v 1 and pathogenesis‐related (PR10) plant food allergens is responsible for the pollen‐food allergy syndrome. Methods: We designed a recombinant protein, AB‐PreS, consisting of non‐allergenic peptides derived from the IgE‐binding sites of Bet v 1 and the cross‐reactive apple allergen, Mal d 1, fused to the PreS domain of HBV surface protein as immunological carrier. AB‐PreS was expressed in E. coli and purified by chromatography. The allergenic and inflammatory activity of AB‐PreS was tested using basophils and PBMCs from birch pollen allergic patients. The ability of antibodies induced by immunization of rabbits with AB‐PreS and birch pollen extract‐based vaccines to inhibit allergic patients IgE binding to Bet v 1 and Mal d 1 was assessed by ELISA. Results: IgE‐binding experiments and basophil activation test revealed the hypoallergenic nature of AB‐PreS. AB‐PreS induced lower T‐cell activation and inflammatory cytokine production in cultured PBMCs from allergic patients. IgG antibodies induced by five injections with AB‐PreS inhibited allergic patients' IgE binding to Bet v 1 and Mal d 1 better than did IgG induced by up to 30 injections of six licensed birch pollen allergen extract‐based vaccines. Additionally, immunization with AB‐PreS induced HBV‐specific antibodies potentially protecting from infection with HBV. Conclusion: The recombinant AB‐PreS‐based vaccine is hypoallergenic and superior over currently registered allergen extract‐based vaccines regarding the induction of blocking antibodies to Bet v 1 and Mal d 1 in animals. [ABSTRACT FROM AUTHOR]

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. The sequence identity of cat albumin (Fel d 2) and dog albumin (Can f 3) and HSA are 82% and 80%, respectively. Given the high degree of sequence identity between the latter two allergens and HSA one would expect that immunological tolerance would prohibit IgE sensitization to Fel d 2 and Can f 3. Here we discuss two possibilities for how IgE sensitization to Fel d 2 and Can f 3 may develop. One possibility is the failed development of immune tolerance in albumin-allergic patients whereas the other possibility is highly selective immune tolerance to HSA but not to Fel d 2 and Can f 3. If the first assumption is correct it should be possible to detect HSAspecific T cell responses and HSA-containing immune complexes in sensitized patients. In the latter scenario few differences in the sequences of Fel d 2 and Can f 3 as compared to HSA would be responsible for the development of selective T cell and B cell responses towards Fel d 2 as well as Can f 3. However, the immunological mechanisms of albumin sensitization have not yet been investigated in detail although this will be important for the development of allergen-specific prevention and allergen-specific immunotherapy (AIT) strategies for allergy to albumin. [ABSTRACT FROM AUTHOR]

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. Results: S‐ and RBD‐specific antibody responses were dominated by immunoglobulin G (IgG), mainly IgG1, and directed against structurally folded S and RBD and three distinct peptide epitopes in S2. The virus neutralization activity of patients´ sera was highly correlated with IgG antibodies specific for conformational but not sequential RBD epitopes and their ability to prevent RBD binding to its human receptor angiotensin‐converting enzyme 2 (ACE2). Twenty percent of patients selectively lacked RBD‐specific IgG. Only immunization with folded, but not with unfolded RBD, induced antibodies against conformational epitopes with high virus‐neutralizing activity. Conformational RBD epitopes required for protection do not seem to be altered in the currently emerging virus variants. Conclusion: These results are fundamental for estimating the protective activity of antibody responses after natural infection or vaccination and for the design of vaccines, which can induce high levels of SARS‐CoV‐2–neutralizing antibodies conferring sterilizing immunity. [ABSTRACT FROM AUTHOR]

Keywords: COVID-19; immune complex; molecular interaction assay; protective antibodies; SARS-CoV-2; vaccine EN COVID-19 immune complex molecular interaction assay protective antibodies SARS-CoV-2 vaccine 878 883 6 03/09/21 20210301 NES 210301 Abbreviations ACE2 angiotensin-converting enzyme 2 COVID-19 coronavirus disease ELISA enzyme-linked immunosorbent assay HRP horseradish peroxidase IgG, IgA, IgM immunoglobulin G, A, M MERS middle east respiratory syndrome OD optical density RBD receptor-binding domain RNA ribonucleic acid RT-PCR reverse transcription polymerase chain reaction RV rhinovirus S spike protein S1 spike protein receptor-binding subunit S2 spike protein membrane fusion subunit SARS severe acute respiratory syndrome After the appearance of first cases in Wuhan, China in December 2019, the novel human coronavirus disease, COVID-19, has become the first coronavirus pandemic in history.1 On 16 July 2020, more than 13.5 million patients worldwide have been infected with the novel coronavirus, SARS-CoV-2, and more than 584.000 global deaths related to COVID-19 have been reported (see: The Center for Systems Science and Engineering (CSSE) at Johns Hopkins University, Baltimore: https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6). However, in 2002, severe acute respiratory syndrome (SARS) (Group IIb) and, in 2012, Middle East respiratory syndrome (MERS) (Group IIc) were shown to be caused by the novel coronaviruses, SARS-CoV and MERS-CoV, respectively, which caused high death rates in up to 10% of infected people.1 Like SARS-CoV, SARS-CoV-2 uses angiotensin-converting enzyme 2, ACE2 on human cells as its receptor2 and binds to it with its receptor-binding domain (RBD). It has been shown that COVID-19 patients develop SARS-CoV-2-specific antibodies but it is not known if and in how many infected subjects the virus-induced antibodies are protective. [Extracted from the article]

Background: SARS‐CoV‐2 has triggered a pandemic that is now claiming many lives. Several studies have investigated cellular immune responses in COVID‐19‐infected patients during disease but little is known regarding a possible protracted impact of COVID‐19 on the adaptive and innate immune system in COVID‐19 convalescent patients. Methods: We used multiparametric flow cytometry to analyze whole peripheral blood samples and determined SARS‐CoV‐2‐specific antibody levels against the S‐protein, its RBD‐subunit, and viral nucleocapsid in a cohort of COVID‐19 convalescent patients who had mild disease ~10 weeks after infection (n = 109) and healthy control subjects (n = 98). Furthermore, we correlated immunological changes with clinical and demographic parameters. Results: Even ten weeks after disease COVID‐19 convalescent patients had fewer neutrophils, while their cytotoxic CD8+ T cells were activated, reflected as higher HLA‐DR and CD38 expression. Multiparametric regression analyses showed that in COVID‐19‐infected patients both CD3+CD4+ and CD3+CD8+ effector memory cells were higher, while CD25+Foxp3+ T regulatory cells were lower. In addition, both transitional B cell and plasmablast levels were significantly elevated in COVID‐19‐infected patients. Fever (duration, level) correlated with numbers of central memory CD4+ T cells and anti‐S and anti‐RBD, but not anti‐NC antibody levels. Moreover, a "young immunological age" as determined by numbers of CD3+CD45RA+CD62L+CD31+ recent thymic emigrants was associated with a loss of sense of taste and/or smell. Conclusion: Acute SARS‐CoV‐2 infection leaves protracted beneficial (ie, activation of T cells) and potentially harmful (ie, reduction of neutrophils) imprints in the cellular immune system in addition to induction of specific antibody responses. [ABSTRACT FROM AUTHOR]

Allergen‐specific immunotherapy (AIT) is an allergen‐specific form of treatment for patients suffering from immunoglobulin E (IgE)‐associated allergy; the most common and important immunologically mediated hypersensitivity disease. AIT is based on the administration of the disease‐causing allergen with the goal to induce a protective immunity consisting of allergen‐specific blocking IgG antibodies and alterations of the cellular immune response so that the patient can tolerate allergen contact. Major advantages of AIT over all other existing treatments for allergy are that AIT induces a long‐lasting protection and prevents the progression of disease to severe manifestations. AIT is cost effective because it uses the patient´s own immune system for protection and potentially can be used as a preventive treatment. However, broad application of AIT is limited by mainly technical issues such as the quality of allergen preparations and the risk of inducing side effects which results in extremely cumbersome treatment schedules reducing patient´s compliance. In this article we review progress in AIT made from its beginning and provide an overview of the state of the art, the needs for further development, and possible technical solutions available through molecular allergology. Finally, we consider visions for AIT development towards prophylactic application. [ABSTRACT FROM AUTHOR]