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 IgG 1 , 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.

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.

The blood proteomic signature of early-onset pediatric atopic dermatitis shows systemic inflammation and is distinct from adult long-standing disease.

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 IgG 1 responses in vaccinated subjects whereas the PreS‐RBD vaccine induced RBD‐specific IgG antibodies consisting of an early IgG 1 and sustained IgG 4 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.

Disclosure of potential conflict of interest K. Niespodziana receives grant support (grant no. P29398) from the Austrian Science Foundation (FWF). K. F. Chung has received honoraria for participating in advisory board meetings of GlaxoSmithKline (GSK), AstraZeneca, Novartis, Merck, Boehringer Ingelheim, and Teva regarding treatments for asthma and chronic obstructive pulmonary disease and has also been renumerated for speaking engagements. A. Custovic reports personal fees from Novartis,