Antibody profiling reveals gender differences in response to SARS-COVID-2 infection

<abstract> <p>The recent emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to an ongoing global COVID-19 pandemic and public health crisis. Detailed study of human immune response to SARS-CoV-2 infection is the important topic for a successful treatment of this disease. Our study was aimed to characterize immune response on the level of antibody profiling in convalescent plasma of patients in Georgia. Antibodies against the following SARS-CoV-2 proteins were studied: nucleocapsid and various regions of spike (S) protein: S1, S2 and receptor binding domain (RBD). Convalescent plasma of patients 6–8 weeks after initial confirmation of SARS-CoV-2 infection were tested. Nearly 80% out of 162 patients studied showed presence of antibodies against nucleocapsid protein. The antibody response to three fragments of S protein was significantly less and varied in the range of 20–30%. Significantly more females as compared to males were producing antibodies against S1 fragment, whereas the difference between genders by the antibodies against nucleocapsid protein and RBD was statistically significant only by one-tailed Fisher exact test. There were no differences between the males and females by antibodies against S2 fragment. Thus, immune response against some viral antigens is stronger in females and we suggest that it could be one of the factors of less female fatality after SARS-CoV-2 infection.</p> </abstract>

Macaque-human differences in SARS-CoV-2 Spike antibody response elicited by vaccination or infection

Macaques are a commonly used model for studying immunity to human viruses, including for studies of SARS-CoV-2 infection and vaccination. However, it is unknown whether macaque antibody responses recapitulate, and thus appropriately model, the response in humans. To answer this question, we employed a phage-based deep mutational scanning approach (Phage- DMS) to compare which linear epitopes are targeted on the SARS-CoV-2 Spike protein in humans and macaques following either vaccination or infection. We also used Phage-DMS to determine antibody escape pathways within each epitope, enabling a granular comparison of antibody binding specificities at the locus level. Overall, we identified some common epitope targets in both macaques and humans, including in the fusion peptide (FP) and stem helix- heptad repeat 2 (SH-H) regions. Differences between groups included a response to epitopes in the N-terminal domain (NTD) and C-terminal domain (CTD) in vaccinated humans but not vaccinated macaques, as well as recognition of a CTD epitope and epitopes flanking the FP in convalescent macaques but not convalescent humans. There was also considerable variability in the escape pathways among individuals within each group. Sera from convalescent macaques showed the least variability in escape overall and converged on a common response with vaccinated humans in the SH-H epitope region, suggesting highly similar antibodies were elicited. Collectively, these findings suggest that the antibody response to SARS-CoV-2 in macaques shares many features with humans, but with substantial differences in the recognition of certain epitopes and considerable individual variability in antibody escape profiles, suggesting a diverse repertoire of antibodies that can respond to major epitopes in both humans and macaques.Author summaryNon-human primates, including macaques, are considered the best animal model for studying infectious diseases that infect humans. Vaccine candidates for SARS-CoV-2 are first tested in macaques to assess immune responses prior to advancing to human trials, and macaques are also used to model the human immune response to SARS-CoV-2 infection. However, there may be differences in how macaque and human antibodies recognize the SARS-CoV-2 entry protein, Spike. Here we characterized the locations on Spike that are recognized by antibodies from vaccinated or infected macaques and humans. We also made mutations to the viral sequence and assessed how these affected antibody binding, enabling a comparison of antibody binding requirements between macaques and humans at a very precise level. We found that macaques and humans share some responses, but also recognize distinct regions of Spike. We also found that in general, antibodies from different individuals had unique responses to viral mutations, regardless of species. These results will yield a better understanding of how macaque data can be used to inform human immunity to SARS-CoV-2.

Association of Parvovirus B19 with Rheumatic Diseases

Human parvovirus B19 infections are well reported to be associated with different autoimmune disorders. They can either mimic or trigger autoimmune diseases, such as systemic lupus erythematous (SLE), rheumatoid arthritis (RA), and vasculitis. A lack of awareness about this infection can result in delays in diagnosis and poor care. In this review, the basic biology and clinical aspects of the parvovirus, human immune response, and the pathogenesis in the rheumatic diseases are discussed.

Characterization of an In Vivo Neutralizing Anti-Vaccinia Virus D8 Single-Chain Fragment Variable (scFv) from a Human Anti-Vaccinia Virus-Specific Recombinant Library

A panel of potent neutralizing antibodies are protective against orthopoxvirus (OPXV) infections. For the development of OPXV-specific recombinant human single-chain antibodies (scFvs), the IgG repertoire of four vaccinated donors was amplified from peripheral B-lymphocytes. The resulting library consisted of ≥4 × 108 independent colonies. The immuno-screening against vaccinia virus (VACV) Elstree revealed a predominant selection of scFv clones specifically binding to the D8 protein. The scFv-1.2.2.H9 was engineered into larger human scFv-Fc-1.2.2.H9 and IgG1-1.2.2.H9 formats to improve the binding affinity and to add effector functions within the human immune response. Similar binding kinetics were calculated for scFv-1.2.2.H9 and scFv-Fc-1.2.2.H9 (1.61 nM and 7.685 nM, respectively), whereas, for IgG1-1.2.2.H9, the Michaelis-Menten kinetics revealed an increased affinity of 43.8 pM. None of the purified recombinant 1.2.2.H9 formats were able to neutralize VACV Elstree in vitro. After addition of 1% human complement, the neutralization of ≥50% of VACV Elstree was achieved with 0.0776 µM scFv-Fc-1.2.2.H9 and 0.01324 µM IgG1-1.2.2.H9, respectively. In an in vivo passive immunization NMRI mouse model, 100 µg purified scFv-1.2.2.H9 and the IgG1-1.2.2.H9 partially protected against the challenge with 4 LD50 VACV Munich 1, as 3/6 mice survived. In contrast, in the scFv-Fc-1.2.2.H9 group, only one mouse survived the challenge.

In vitro analysis of human immune response (IgG) against salivary gland extract of dengue vector from dengue hemorrhagic fever (DHF) endemic area in Jember, Indonesia

The mosquito species Ae. aegyptiand Ae. albopictusare two potential vectors of dengue fever. The salivary glands of these species contain substances that play a role in the transmission of pathogens. These include vasodilators and immunomodulatory compounds. Immunomodulatory components can modulate the host immune system by producing specific antibodies (IgG). This study aims to investigate the human immune response (IgG) against the salivary gland extract of Ae. aegyptiand Ae. albopictus. Samples were collected from individuals who were Dengue patients, as well as healthy individuals and neonates from the Jember endemic area. Results show that the levels of IgG response vary across the individual. Generally, Dengue patients and healthy people in the DHF-endemic area had higher levels of IgG. The highest immune response was found in DHF patients, followed by healthy persons, and finally the neonate samples, respectively.

COVID-19 Mechanisms in the Human Body—What We Know So Far

More than one and a half years have elapsed since the commencement of the coronavirus disease 2019 (COVID-19) pandemic, and the world is struggling to contain it. Being caused by a previously unknown virus, in the initial period, there had been an extreme paucity of knowledge about the disease mechanisms, which hampered preventive and therapeutic measures against COVID-19. In an endeavor to understand the pathogenic mechanisms, extensive experimental studies have been conducted across the globe involving cell culture-based experiments, human tissue organoids, and animal models, targeted to various aspects of the disease, viz., viral properties, tissue tropism and organ-specific pathogenesis, involvement of physiological systems, and the human immune response against the infection. The vastly accumulated scientific knowledge on all aspects of COVID-19 has currently changed the scenario from great despair to hope. Even though spectacular progress has been made in all of these aspects, multiple knowledge gaps are remaining that need to be addressed in future studies. Moreover, multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have emerged across the globe since the onset of the first COVID-19 wave, with seemingly greater transmissibility/virulence and immune escape capabilities than the wild-type strain. In this review, we narrate the progress made since the commencement of the pandemic regarding the knowledge on COVID-19 mechanisms in the human body, including virus–host interactions, pulmonary and other systemic manifestations, immunological dysregulations, complications, host-specific vulnerability, and long-term health consequences in the survivors. Additionally, we provide a brief review of the current evidence explaining molecular mechanisms imparting greater transmissibility and virulence and immune escape capabilities to the emerging SARS-CoV-2 variants.

Host and Bacterial Iron Homeostasis, an Underexplored Area in Tuberculosis Biomarker Research

Mycobacterium tuberculosis (Mtb) “a human adapted pathogen” has found multiple ways to manipulate the host immune response during infection. The human immune response to Mtb infection is a highly complex cascade of reactions, with macrophages as preferred intracellular location. Interaction with the host through infection gives rise to expression of specific gene products for survival and multiplication within the host. The signals that the pathogens encounter during infection cause them to selectively express genes in response to signals. One strategy to identify Mtb antigens with diagnostic potential is to identify genes that are specifically induced during infection or in specific disease stages. The shortcomings of current immunodiagnostics include the failure to detect progression from latent infection to active tuberculosis disease, and the inability to monitor treatment efficacy. This highlights the need for new tuberculosis biomarkers. These biomarkers should be highly sensitive and specific diagnosing TB infection, specifically distinguishing between latent infection and active disease. The regulation of iron levels by the host plays a crucial role in the susceptibility and outcome of Mtb infection. Of interest are the siderophore biosynthetic genes, encoded by the mbt-1 and mbt-2 loci and the SUF (mobilization of sulphur) operon (sufR-sufB-sufD-sufC-csd-nifU-sufT), which encodes the primary iron-sulphur cluster biogenesis system. These genes are induced during iron limitation and intracellular growth of Mtb, pointing to their importance during infection.

Life span of Covid-19 antibodies following infection in a sample worker population in Qatar

Background: COVID-19 antibodies’ longevity following infection is still unclear. Early data brought hope that acquired immunity was possible but subsequent studies suggested that immune protection might be short-lived. The results of recent studies provide greater insight into the human immune response to COVID-19. The Qatar Gas medical department’s strategy in preventing spread of infection among offshore and onshore workers consisted of maximizing the opportunities for COVID-19 polymerise chain reaction (PCR) and antibody testing. A large amount of data revealing the possible lifespan of COVID-19 antibodies in the study population was collected. Methods: Out of hundreds of employees who volunteered in this study about seroprevalance of COVID-19 antibodies, 52 whose results were reactive were tested for COVID-19 PCR before being selected. Employees with reactive or inconclusive PCR test results were excluded. Age, medical/surgical/social history, apart from past COVID-19 infection, were not selection criteria. We measured the period of time between the date of diagnosis and the antibody test result, segregating those still reactive from those who tested non-reactive at any point in time. The reactive group were retested for antibodies every 90 days as long as results continued to be reactive. Any cured employee was retested if they developed symptoms or was exposed to a confirmed positive case, to rule out the possibility of re-infection during this timeframe. Results: Only one employee was non-reactive after 110 days of COVID-19 PCR positive test result. 22 employees tested reactive although their PCR result had been negative. 30 employees tested reactive after a positive PCR with an average duration of 145 days, the shortest and longest being 24 and 223 respectively. Conclusion: We determined that antibodies’ longevity may extend to more than 6 months following COVID-19 infection and that there may be an early decay of antibodies in a limited proportion of the population, however further studies are recommended on larger populations. We noticed no cases of COVID-19 reinfection.

Cross Talk on SARS-CoV-2 and Human Immunity

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19) is now the leading cause of death globally. This review elaborated the human immune response to SARSCoV-2 and its immune evasion mechanisms as well as factors that determine the case fatality rate and effective immunity using articles selected from PubMed, Medline, Google Scholar and Science Direct that provided an in-depth knowledge of the immunopathogenesis of SARS-CoV-2. Findings from the forty eligible reviewed articles revealed that the host-viral interaction to SARS-CoV-2 involves the recognition of SARS-CoV-2, recruitment of adaptor proteins and antigen presentation which activates both innate and adaptive immunity involved in inhibition of viral replication (interferons), destruction of virus-infected cells (natural killer cells and CD8 cells) and viral clearance. However, SARS-CoV-2 subverts human immunity using multiple strategies such as production of double membrane vesicles, repression of adaptor proteins, interferons and antigen presentation. Accumulating shreds of evidence have shown that several factors such as age, sex, comorbidities, obesity, and lifestyle factors affect immune responsiveness to SARS-CoV-2. Hence, better knowledge of the viral interactions with the host and factors determining prevalence and severity is fundamental to the management and development of effective and biocompatible prophylactic and therapeutic options.