Dynamics Of Humoral Immune Response Research Articles

Antibodies to SARS-CoV2 induced by vaccination and infection correlate with protection against the infection

The COVID-19 pandemic remained worldwide for almost three years, but little is known about the dynamics of humoral immune response to the third dose over time and its protection from infection. Our aim was to assess the humoral immune response after the third dose of the different vaccines administered to SARS-CoV-2 naive and previously infected individuals, and its correlation with protection in an academic community.For each person studied (185), three blood samples were taken between December 2021 and July 2022, one month apart. Anti-S antibodies were quantified by ELISA, while anti-N antibody levels were determined by ECLIA. Most of the participants had received two doses of viral vector-based, mRNA-based and virus-inactivated vaccines.Although anti-N antibody levels revealed that 80% of the individuals had been exposed to the virus before or during the study, only 42% reported having been diagnosed.When anti-S IgG levels were measured 3–5 months after the second dose of any vaccine, they were higher in those previously infected individuals. The same results were observed for anti-N IgG levels in those who received 2 doses of the virus-inactivated vaccine.When analyzing the dynamics of anti-S antibodies we observed that, although positive IgG antibody levels were detected 5–6 months after the second dose administration, those observed 30–60 days after the third dose were significantly higher and remained so for at least 8 months.Higher levels of anti-S IgG antibodies at the first sampling were associated with a lower incidence of subsequent infection. The same association was seen in people who received the booster compared with those who received two doses.This study provides further evidence that anti-S IgG antibodies remained at high levels over time, and both anti-S levels and the third dose of anti-SARS-CoV-2 vaccine correlate with protection against the infection. It also shows that infection acts as a booster of immunization, increasing levels of both anti-N and anti-S IgG.

Dynamics of Antibody Responses after Asymptomatic and Mild to Moderate SARS-CoV-2 Infections: Real-World Data in a Resource-Limited Country.

The dynamics of humoral immune responses of patients after SARS-CoV-2 infection is unclear. This study prospectively observed changes in anti-receptor binding domain immunoglobulin G (anti-RBD IgG) and neutralizing antibodies against the Wuhan and Delta strains at 1, 3, and 6 months postinfection between October 2021 and May 2022. Demographic data, clinical characteristics, baseline parameters, and blood samples of participants were collected. Of 5059 SARS-CoV-2 infected adult patients, only 600 underwent assessment at least once between 3 and 6 months after symptom onset. Patients were categorized as immunocompetent (n = 566), immunocompromised (n = 14), or reinfected (n = 20). A booster dose of a COVID-19 vaccine was strongly associated with maintained or increased COVID-19 antibody levels. The booster dose was also more strongly associated with antibody responses than the primary vaccination series. Among patients receiving a booster dose of a mRNA vaccine or a heterologous regimen, antibody levels remained steady or even increased for 3 to 6 months after symptom onset compared with inactivated or viral vector vaccines. There was a strong correlation between anti-RBD IgG and neutralizing antibodies against the Delta variant. This study is relevant to resource-limited countries for administering COVID-19 vaccines 3 to 6 months after infection.

Dynamics of humoral immune response in SARS-CoV-2 infected individuals with different clinical stages.

The COVID-19 pandemic remains a global health problem. As in other viral infections, the humoral immune response against SARS-CoV-2 is thought to be crucial for controlling the infection. However, the dynamic of B cells in the clinical spectrum of this disease is still controversial. This study aimed to characterize B cell subsets and neutralizing responses in COVID-19 patients according to disease severity through a one-month follow-up. A cohort of 71 individuals with SARS-CoV-2 infection confirmed by RT-PCR were recruited and classified into four groups: i) asymptomatic; ii) symptomatic outpatients; iii) hospitalized in ward, and iv) intensive care unit patients (ICU). Samples were taken at days 0 (inclusion to the study), 7 and 30. B cell subsets and neutralizing antibodies were assessed using multiparametric flow cytometry and plaque reduction neutralization, respectively. Older age, male gender and body mass index over 25 were common factors among hospitalized and ICU patients, compared to those with milder clinical presentations. In addition, those requiring hospitalization had more comorbidities. A significant increase in the frequencies of CD19+ cells at day 0 was observed in hospitalized and ICU patients compared to asymptomatic and symptomatic groups. Likewise, the frequency of plasmablasts was significantly increased at the first sample in the ICU group compared to the asymptomatic group, but then waned over time. The frequency of naïve B cells decreased at days 7 and 30 compared to day 0 in hospitalized and ICU patients. The neutralizing antibody titers were higher as the severity of COVID-19 increased; in asymptomatic individuals, it was strongly correlated with the percentage of IgM+ switched memory B cells, and a moderate correlation was found with plasmablasts. The humoral immune response is variable among SARS-CoV-2 infected people depending on the severity and time of clinical evolution. In severe COVID-19 patients, a higher plasmablast frequency and neutralizing antibody response were observed, suggesting that, despite having a robust humoral immunity, this response could be late, having a low impact on disease outcome.

Longitudinal determination of BNT162b2 vaccine induced strongly binding SARS-CoV-2 IgG antibodies in a cohort of Romanian healthcare workers

Mass vaccination against the disease caused by the novel coronavirus (COVID-19) was a crucial step in slowing the spread of SARS-CoV-2 in 2021. Even in the face of new variants, it still remains extremely important for reducing hospitalizations and COVID-19 deaths. In order to better understand the short- and long-term dynamics of humoral immune response, we present a longitudinal analysis of post-vaccination IgG levels in a cohort of 166 Romanian healthcare workers vaccinated with BNT162b2 with weekly follow-up until 35 days past the first dose and monthly follow-up up to 6 months post-vaccination. A subset of the patients continued with follow-up after 6 months and either received a booster dose or got infected during the Delta wave in Romania. Tests were carried out on 1694 samples using a CE-marked IgG ELISA assay developed in-house, containing S1 and N antigens of the wild type virus.Participants infected with SARS-CoV-2 before vaccination mount a quick immune response, reaching peak IgG levels two weeks after the first dose, while IgG levels of previously uninfected participants mount gradually, increasing abruptly after the second dose. Overall higher IgG levels are maintained for the previously infected group throughout the six month primary observation period (e.g. 36–65 days after the first dose, the median value in the previously infected group is 5.29 AU/ml, versus 3.58 AU/ml in the infection naïve group, p less than 0.001). The decrease of IgG levels is gradual, with lower median values in the infection naïve cohort even 7–8 months after vaccination, compared to the previously infected cohort (0.7 AU/ml versus 1.29 AU/ml, p = 0.006). Administration of a booster dose yielded higher median IgG antibody levels than post second dose in the infection naïve group and comparable levels in the previously infected group.

Longitudinal Dynamics of SARS-CoV-2 IgG Antibody Responses after the Two-Dose Regimen of BNT162b2 Vaccination and the Effect of a Third Dose on Healthcare Workers in Japan.

Analysis of longitudinal dynamics of humoral immune responses to the BNT162b2 COVID-19 vaccine might provide useful information to predict the effectiveness of BNT162b2 in preventing SARS-CoV-2 infection. Herein, we measure anti-RBD IgG at 1, 3 and 6 months (M) after the second dose of BNT162b2, and at 1 M after a third dose of BNT162b2 vaccination in 431 COVID-19-naïve healthcare workers (HCWs) in Japan. All HCWs mounted high-anti-RBD IgG responses after the two-dose regimen of BNT162b2 vaccinations. Older persons and males presented lower anti-RBD IgG responses than younger adults and females, respectively. The decay in anti-RBD IgG started from 1 M after the second dose of BNT162b2 and anti-RBD IgG titers dropped to nearly one-tenth at 6 M after the second vaccination. Subsequently, the participants received a third dose of BNT162b2 at 8 M after the second dose of BNT162b2 vaccine. Anti-RBD antibody titers 1 M after the third dose of BNT162b2 increased seventeen times that of 6 M after the second dose, and was twice higher than the peak antibody titers at 1 M after the second dose of vaccination. The negative effect of age for the male gender on anti-RBD IgG antibody titers was not observed at 1 M after the third dose of BNT162b2 vaccine. There were no notable adverse events reported, which required hospitalization in these participants. These results suggest that the third dose of BNT162b2 safely improves humoral immunity against SARS-CoV-2 with no major adverse events.

Evaluation of Spike Protein Epitopes by Assessing the Dynamics of Humoral Immune Responses in Moderate COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic is caused by a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The spike protein (S) of SARS-CoV-2 is a major target for diagnosis and vaccine development because of its essential role in viral infection and host immunity. Currently, time-dependent responses of humoral immune system against various S protein epitopes are poorly understood. In this study, enzyme-linked immunosorbent assay (ELISA), peptide microarray, and antibody binding epitope mapping (AbMap) techniques were used to systematically analyze the dynamic changes of humoral immune responses against the S protein in a small cohort of moderate COVID-19 patients who were hospitalized for approximately two months after symptom onset. Recombinant truncated S proteins, target S peptides, and random peptides were used as antigens in the analyses. The assays demonstrated the dynamic IgM- and IgG recognition and reactivity against various S protein epitopes with patient-dependent patterns. Comprehensive analysis of epitope distribution along the spike gene sequence and spatial structure of the homotrimer S protein demonstrated that most IgM- and IgG-reactive peptides were clustered into similar genomic regions and were located at accessible domains. Seven S peptides were generally recognized by IgG antibodies derived from serum samples of all COVID-19 patients. The dynamic immune recognition signals from these seven S peptides were comparable to those of the entire S protein or truncated S1 protein. This suggested that the humoral immune system recognized few conserved S protein epitopes in most COVID-19 patients during the entire duration of humoral immune response after symptom onset. Furthermore, in this cohort, individual patients demonstrated stable immune recognition to certain S protein epitopes throughout their hospitalization period. Therefore, the dynamic characteristics of humoral immune responses to S protein have provided valuable information for accurate diagnosis and immunotherapy of COVID-19 patients.

Efficacy of mRNA anti-SARS-CoV-2 vaccination and dynamics of humoral immune response in patients with solid tumors: results from the institutional registry of an Italian tertiary cancer center.

Background:Systemic immunosuppression characterizing cancer patients represents a concern regarding the efficacy of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, and real-world evidence is needed to define the efficacy and the dynamics of humoral immune response to mRNA-based anti-SARS-CoV-2 vaccines.Methods:We conducted an observational study that included patients with solid tumors who were candidates for mRNA anti-SARS-CoV-2 vaccination at the Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. The primary objective was to monitor the immunologic response to the mRNA anti-SARS-CoV-2 vaccination in terms of anti-spike antibody levels. All the patients received two doses of the mRNA-1273 vaccine or the BNT162b2 vaccine. Healthcare workers served as a control group of healthy subjects.Results:Among the 243 patients included in the present analysis, 208 (85.60%) and 238 (97.94%) resulted seroconverted after the first and the second dose of vaccine, respectively. Only five patients (2.06%) had a negative titer after the second dose. No significant differences in the rate of seroconversion after two vaccine doses were observed in patients as compared with the control group of healthy subjects. Age and anticancer treatment class had an independent impact on the antibody titer after the second dose of vaccination. In a subgroup of 171 patients with available data about the third timepoint, patients receiving immunotherapy with immune checkpoint inhibitors seem to have a higher peak of antibodies soon after the second dose (3 weeks after), but a more pronounced decrease at a late timepoint (3 months after).Conclusions:The systemic immunosuppression characterizing cancer patients did not seem to dramatically affect the humoral response to anti-SARS-CoV-2 mRNA vaccines in our population of patients with solid tumors. Further investigation is needed to dissect the interplay between immunotherapy and longitudinal dynamics of humoral response to mRNA vaccines, as well as to analyze the cellular response to mRNA vaccines in cancer patients.

Retrospective of International Serological Studies on the Formation and Dynamics of the Humoral Immune Response to SARS-CoV-2: from 2020 to 2021

Last year the COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has started. The new coronavirus is highly contagious and causes severe complications. The mechanisms of humoral immunity and kinetics of SARS-CoV-2 specific antibodies in a population are not well understood. Therefore, we aimed to summarize and analyze numerous global and Russian serological studies for understanding dynamics of the SARSCoV-2 humoral immune response and getting an accurate picture of the seroprevalence to SARS-CoV-2 in the world population. The PubMed and e-library databases were searched from February 2020 to March 2021 using terms “SARSCoV-2”, “antibodies”, “humoral immunity”. At the beginning of the pandemic first studies were cross-sectional by design and were responsible for determination of the seropositivity and for understanding the fundamental humoral immunity parameters of SARS-CoV-2. Since then, longitudinal seroepidemiological studies have been studying antibody kinetics. Seroconversion time for IgM, IgG antibodies varies, but most researchers report the seroconversion of IgM from the 1st to 14th days after the onset of clinical manifestations, and the seroconversion for IgG is around the 14th day with a concentration peak by the 21st day. Regarding seroprevalence we may say about low herd immunity at the COVID-19 pandemic. Thus, global seroprevalence is about 10 %, and more than 20 % for regions with high incidence and among healthcare workers. Seroprevalence studies have to be continued for more accurate monitoring of long-term humoral immunity to SARS-CoV-2, because the majority of the world’s population is still susceptible to SARS-CoV-2 infection.

The dynamics of humoral immune responses following SARS-CoV-2 infection and the potential for reinfection.

SARS-CoV-2 is a novel coronavirus that is the causative agent of coronavirus infectious disease 2019 (COVID-19). As of 17 April 2020, it has infected 2 114 269 people, resulting in 145 144 deaths. The timing, magnitude and longevity of humoral immunity is not yet understood for SARS-CoV-2. Nevertheless, understanding this is urgently required to inform the likely future dynamics of the pandemic, to guide strategies to allow relaxation of social distancing measures and to understand how to deploy limiting vaccine doses when they become available to achieve maximum impact. SARS-CoV-2 is the seventh human coronavirus to be described. Four human coronaviruses circulate seasonally and cause common colds. Two other coronaviruses, SARS and MERS, have crossed from animal sources into humans but have not become endemic. Here we review what is known about the human humoral immune response to epidemic SARS CoV and MERS CoV and to the seasonal, endemic coronaviruses. Then we summarize recent, mostly non-peer reviewed, studies into SARS-CoV-2 serology and reinfection in humans and non-human primates and summarize current pressing research needs.

Quantitative Mass Spectrometric Analysis of Autoantibodies as a Paradigm Shift in Autoimmune Serology.

Affecting ~7–9% of individuals worldwide (1), autoimmunity is a relatively common condition that can cause substantial morbidity and mortality (2). However, there are considerable challenges in finding robust and accurate biomarkers for this heterogeneous group of diseases. Serum autoantibodies have served as archetypal diagnostic biomarkers for autoimmune diseases over decades (3). As pathologic species, they can be used to monitor disease activity and treatment responses (4). Most diagnostic laboratory tests for autoantibodies utilize conventional assays such as the solid-phase enzyme immunoassay (EIA), enzyme-linked immunosorbent assay (ELISA), or radioimmunoassay (RIA). All of these assays quantitate amounts of autoantibodies in the bodily fluid but fail to delineate their molecular composition. Multiplex assays have emerged for autoantibody high-throughput screening that enable rapid identification of subsets of patients to facilitate diagnostic and predictive medicine (5). This is particularly important since multiple autoantibodies are often responsible for autoimmune disease (6). However, such conventional assays cannot unravel clonal evolution and dynamic autoimmune responses. Frustratingly, prediction of disease onset and flares with these biomarkers remains suboptimal. Mass spectrometry (MS) is an analytical technique which can identify proteins by determining the amino acid sequence of peptides derived from each protein. MS can also measure changes in relative abundance of specific proteins as a consequence of treatment, and with appropriate standards, quantify absolute abundance. MS has been used previously to analyze specific antibodies or the repertoire of antibodies in order to better understand the dynamics of humoral immune responses in vaccinated animals (7). This technology has been used to characterize autoantibodies in diseases such as systemic lupus erythematosus (SLE) and Sjogren's syndrome (SS) by identifying their immunoglobulin variable region (IgV) subfamily usage and mutational profiles at a molecular level (8). Despite conventional immunoassays determining stability in autoantibody profiles, MS-based quantitative proteomics has been used to uncover the dynamic changes in molecular signatures and levels of autoantibodies as the disease progresses (9). Subtle nuances in the molecular profile of patient autoantibodies can be identified, paving the way for new diagnostic biomarkers that can anticipate the onset or severity of disease before conventional biomarkers or immunoassays (10). This exciting technology hence offers a unique opportunity to identify pathogenic “rogue” and/or protective clonotypes that characterize autoimmune diseases. By deconstructing these clonotypes by quantitative proteomics and establishing a database of clonotypes with their corresponding pathogenicity, this would possibly facilitate identification of at-risk patients for deterioration, or predict response to targeted therapy.

Dynamics of humoral immune response in pregnant mares and foals vaccinated with Theileria equi recombinant EMA-2

ABSTRACT: Theileria equi is an infectious hemoprotozoan agent of equine piroplasmosis, a disease that has severe economic and sanitary impact internationally. In addition to its common clinical features, piroplasmosis can cause gestational losses and neonatal damage, which makes neonates susceptible to this disease. The aim of this study was to evaluate the dynamics of humoral immune response to recombinant EMA-2 of T. equi in pregnant mares and foals, as well as the transfer of vaccine antibodies through the colostrum ingested by sucking foals. For vaccine production, the EMA-2 expression gene was cloned and expressed in the yeast species, Pichia pastoris. Thirty-six horses were used, of which 18 were pregnant mares and 18 were foals. The mares were divided into control and vaccinated groups, and the vaccinated group received three doses of rEMA-2 every 21 days starting at 300 days of gestation. Foals from vaccinated and control groups were evaluated until the sixth month of life. The production of antibodies by foals on the rEMA-2 vaccination schedule was also evaluated from the second month of life. Foals in the vaccinated group had received three doses of the vaccine every 21 days. The method used to evaluate serum and colostrum samples was indirect ELISA, and plates were sensitized with the rEMA-2 protein. At the end of the vaccination schedule, vaccinated mares showed a 2.3-fold increase in antibody levels when compared to baseline values. The colostrum of vaccinated mares presented antibody levels of 1.0432±0.33. Foals delivered by vaccinated mares presented levels of antibodies greater than those of foals delivered by control mares after their first time sucking (at about twelve hours after birth). Foals vaccinated in the second month of life showed an 8.3-fold increase in antibody levels when compared to baseline values. The vaccination schedule with rEMA-2 was able to stimulate humoral immunity in pregnant mares. Vaccine immunoglobins were concentrated in the colostrum of vaccinated mares and foals delivered by these mares showed an increase in serum levels of vaccine antibodies after the first-time sucking.

Systemic and Local Antibody Responses after Experimental Infection withActinobacillus pleuropneumoniaein Piglets with Passive or Active Immunity

The objectives of the present study was to describe different dynamics of humoral immune responses to experimental infection in piglets of different stages of infection and immunity. Two groups of piglets originating from non-immune (group 1) and immune (group 2) sows at the age of 3 weeks were subdivided as follows: a half of each group of piglets was exposed to a low-dose infection with Actinobacillus pleuropneumoniae (APP) strain 9. At the age of 8 weeks, all four groups of piglets were challenged with a high infection dose of APP of the same strain. Isotype characterization of the specific antibodies in sera and in bronchoalveolar lavage fluids (BALF) to a lipopolysaccharide was carried out, besides monitoring clinical signs and post-mortem examinations. A typical primary immune response was observed in specific antibody-free piglets infected with a challenge infection. Colostrum-derived immunoglobulin-G (IgG) antibodies persisted in sera and BALF of piglets up to the age of 8 weeks. However, they did not prevent induction of specific-primary antibody response, either in 8 or 4 weeks of age, when levels of specific colostrum-derived antibodies were still high. It was demonstrated by the increase of specific IgM antibodies in sera. The infection induced an increase in the levels of IgA antibodies in BALF regardless the severity of infection and presence of specific colostrum-derived antibodies. The specific antibodies of IgG isotype increased only in BALF from piglets without colostrum-derived antibodies.

The role of serology in the diagnosis and prognosis of visceral leishmaniasis in patients coinfected with human immunodeficiency virus type-1.

To define the possible role of serology in the diagnosis and prognosis of visceral leishmaniasis (VL) in patients with human immunodeficiency virus type-1 (HIV-1) infection, the dynamics of humoral immune responses was investigated in 20 coinfected patients. Sequential sera obtained before, during, and after VL diagnosis were analyzed by an indirect immunofluorescent antibody test (IFAT), a recombinant ELISA (using the rK39 protein), and immunoblotting. During the active course of the disease, positive results were found by IFAT or ELISA in 22% of the cases and by immunoblotting in 78% of the cases. A great variability in the response was observed during the follow-up with a trend to more positive results near the time of VL diagnosis. Forty-six percent of the patients were positive by IFAT or ELISA on at least one time point before VL and 37.5% were positive during the period following treatment. These results confirm the limited usefulness of the IFAT and ELISA in the diagnosis of VL in coinfected patients and demonstrate their low ability to predict the development or the outcome of disease. In these patients, immunoblotting could be a useful tool for studying the natural course of leishmaniasis, although it has limited value for diagnosis or treatment control.