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Background: Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is responsible for the ongoing global COVID‐19 pandemic. One possibility to control the pandemic is to induce sterilizing immunity through the induction and maintenance of neutralizing antibodies preventing SARS‐CoV‐2 from entering human cells to replicate in. Methods: We report the construction and in vitro and in vivo characterization of a SARS‐CoV‐2 subunit vaccine (PreS‐RBD) based on a structurally folded recombinant fusion protein consisting of two SARS‐CoV‐2 Spike protein receptor‐binding domains (RBD) fused to the N‐ and C‐terminus of hepatitis B virus (HBV) surface antigen PreS to enable the two unrelated proteins serving as immunologic carriers for each other. Results: PreS‐RBD, but not RBD alone, induced a robust and uniform RBD‐specific IgG response in rabbits. Currently available genetic SARS‐CoV‐2 vaccines induce mainly transient IgG1 responses in vaccinated subjects whereas the PreS‐RBD vaccine induced RBD‐specific IgG antibodies consisting of an early IgG1 and sustained IgG4 antibody response in a SARS‐CoV‐2 naive subject. PreS‐RBD‐specific IgG antibodies were detected in serum and mucosal secretions, reacted with SARS‐CoV‐2 variants, including the omicron variant of concern and the HBV receptor‐binding sites on PreS of currently known HBV genotypes. PreS‐RBD‐specific antibodies of the immunized subject more potently inhibited the interaction of RBD with its human receptor ACE2 and their virus‐neutralizing titers (VNTs) were higher than median VNTs in a random sample of healthy subjects fully immunized with registered SARS‐CoV‐2 vaccines or in COVID‐19 convalescent subjects. Conclusion: The PreS‐RBD vaccine has the potential to serve as a combination vaccine for inducing sterilizing immunity against SARS‐CoV‐2 and HBV by stopping viral replication through the inhibition of cellular virus entry. [ABSTRACT FROM AUTHOR]

Antibodies from convalescent patients inhibited the binding of RBD-Wuhan and of RBD-Delta to ACE2 significantly stronger than the binding of RBD-Omicron to ACE2 (Figure 1D). Significant differences between groups are indicated. p values: * <0.05, **<0.01, *** <0.001 gl The RBD-specific IgG levels were in agreement with the results obtained regarding the inhibition of the RBD-ACE2 interaction by serum antibodies (Figure 1D-F). In summary, we demonstrate that RBD-Omicron is recognized much less by IgG antibodies from convalescent patients and by subjects immunized with vaccines based on SARS-CoV-2 Wuhan, even when immunized three times. [Extracted from the article]

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]

Vaccines for infectious diseases have improved the life of the human species in a tremendous manner. The principle of vaccination is to establish de novo adaptive immune response consisting of antibody and T cell responses against pathogens which should defend the vaccinated person against future challenge with the culprit pathogen. The situation is completely different for immunoglobulin E (IgE)-associated allergy, an immunologically-mediated hypersensitivity which is already characterized by increased IgE antibody levels and T cell responses against per se innocuous antigens (i.e., allergens). Thus, allergic patients suffer from a deviated hyper-immunity against allergens leading to inflammation upon allergen contact. Paradoxically, vaccination with allergens, termed allergen-specific immunotherapy (AIT), induces a counter immune response based on the production of high levels of allergen-specific IgG antibodies and alterations of the adaptive cellular response, which reduce allergen-induced symptoms of allergic inflammation. AIT was even shown to prevent the progression of mild to severe forms of allergy. Consequently, AIT can be considered as a form of therapeutic vaccination. In this article we describe a strategy and possible road map for the use of an AIT approach for prophylactic vaccination against allergy which is based on new molecular allergy vaccines. This road map includes the use of AIT for secondary preventive vaccination to stop the progression of clinically silent allergic sensitization toward symptomatic allergy and ultimately the prevention of allergic sensitization by maternal vaccination and/or early primary preventive vaccination of children. Prophylactic allergy vaccination with molecular allergy vaccines may allow halting the allergy epidemics affecting almost 30% of the population as it has been achieved for vaccination against infectious diseases. [ABSTRACT FROM AUTHOR]