Specific IgG Levels Research Articles

Kinetics of Maternally Derived Anti-Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antibodies in Infants in Relation to the Timing of Antenatal Vaccination.

BackgroundSARS-CoV-2 infection during early infancy can result in severe disease. We evaluated the durability of maternally-derived anti-SARS-CoV-2 antibodies in infants and its relation to antenatal vaccination timing.MethodsSera were prospectively collected at birth and 3 months after delivery from mother-infant pairs following antenatal BNT162b2 vaccination. SARS-CoV-2 receptor binding domain (RBD)-specific IgG levels and neutralizing activity were evaluated.Results56 mother-infant pairs were included: 15 (26.8%) were vaccinated in the 1st trimester, 16 (28.6%) in the 2nd trimester, and 25 (44.6%) in the 3rd trimester.At the time of delivery, all neonates were positive for anti-RBD-specific IgG with a median concentration of 4046 [IQR 2446-7896] AU/mL, with the highest concentration found after 3rd trimester vaccination (median 6763 [IQR 3857-12561] AU/mL). At 3 months after delivery, anti RBD-specific IgG levels in infants significantly waned with a median concentration of 545 [IQR 344-810] AU/mL (P < 0.001). The half-life of anti-RBD-specific IgG was 66 days among mothers and 30 days among infants. While at the time of delivery, all neonates had detectable neutralizing activity regardless of gestational age at vaccination, at 3-months of age, a higher proportion of infants born to mothers vaccinated in 3rd trimester had persistent neutralizing activity as compared to those born to mothers vaccinated in 2nd trimester.ConclusionsMaternal vaccination leads to efficient transplacental antibody transfer, with persistent anti-SARS-CoV-2 antibodies detected at 3 months of age in all infants. The observed effect of antenatal immunization timing on the kinetics of maternally-derived antibodies may have implications for SARS-CoV-2 vaccination strategies.

Comparison of the humoral and cellular immunity in COVID-19 convalescents

The SARS-CoV-2 virus caused the COVID-19 pandemic is related to the SARS-CoV-1 and MERS coronaviruses, which were resulted in 2003 and 2012 epidemics. Antibodies in patients with COVID-19 emerge 714 days after the onset of symptoms and gradually increase. Because the COVID-19 pandemic is still in progress, it is hard to say how long the immunological memory to the SARS-CoV-2 virus may be retained. The aim of this study was to study a ratio between humoral and cellular immunity against the SARS-CoV-2 S protein in COVID-19 convalescents. There were enrolled 60 adults with mild to moderate COVID-19 2 to 12 months prior to the examination. The control group consisted of 15 adults without COVID-19 or unvaccinated. Specific antibodies to the SARS-CoV-2 virus were determined by ELISA with the SARS-CoV-2-IgG-ELISA-BEST kit. To determine the specific IgG and IgA subclasses, the anti-IgG conjugate from the kit was replaced with a conjugate against the IgG subclasses and IgA. Additional incubation with or without denaturing urea solution was used to determine the avidity of antibodies. Peripheral blood mononuclear cells were isolated by gradient centrifugation, incubated with or without coronavirus S antigen for 20 hours, stained by fluorescently labeled antibodies, and the percentage of CD8highCD107a cells was assessed on flow cytometer BD FACSCanto II. In the control group, neither humoral nor cellular immunity against the SARS-CoV-2 S protein was found. In the group of convalescents, the level of IgG antibodies against the SARS-CoV-2 S protein varies greatly not being strictly associated with the disease duration, with 57% and 43% of COVID-19 patients having high vs. low level of humoral response, respectively. A correlation between level of specific IgG and IgA was r = 0.43. The avidity of antibodies increased over time in convalescents comprising 49.9% at 612 months afterwards. No virus-specific IgG2 and IgG4 subclasses were detected, and the percentage of IgG1 increased over time comprising 100% 612 months after recovery. 50% of the subjects examined had high cellular immunity, no correlations with the level of humoral immunity were found. We identified 4 combinations of humoral and cellular immunity against the SARS-CoV-2 S protein: high humoral and cellular, low humoral and cellular, high humoral and low cellular, and vice versa, low humoral and high cellular immunity.

Durability of SARS-CoV-2 Specific IgG Antibody Responses Following Two Doses of Match and Mixed COVID-19 Vaccines Regimens in Saudi Population.

BackgroundSARS-CoV-2 pandemic continues to threaten the human population with millions of infections and deaths worldwide. Vaccination campaigns undertaken by several countries have resulted in a notable decrease in hospitalization and deaths. However, with the emergence of new virus variants, it is critical to determine the longevity and the protection efficiency provided by the current authorized vaccines.AimThe aims of this study are to provide data about the magnitude of immune responses in individuals fully vaccinated against COVID-19 in Riyadh province of Saudi Arabia. Also, to evaluate the continuity of specific IgG levels and compare the titers in individuals who have been received two doses of the matched and mixed vaccines, including Pfizer and AstraZeneca against SARS-CoV-2 during the period of three to six months. Moreover, we analyze the current state of immune response in terms of antibody responses in thepopulation postvaccination using homogenous or hetrogenous vaccine regimen.MethodsA total of 141 healthy volunteers were recruited to our study; blood (n=63) and the saliva samples (n=78) and were collected from fully vaccinated individuals in Riyadh city. We employed a specific ELISA assay in plasma and saliva of fully vaccinated individuals.ResultsIgG levels varied with age groups with the highest concentration in the age group 19–29 years, but the age group (≥50) had the lowest IgG concentration. The IgG levels in both serum and saliva were higher after three months and start to wane after six months. Individuals who received mixed types of vaccines had significantly better response than Pfizer vaccine alone.ConclusionThe current study investigates the status of humoral responses in different age groups, in terms of antibody measurements. These data will help to evaluate the need for further COVID-19 vaccine doses and to what extent a two-dose regimen will protect vaccinated individuals.

Natural and Induced Tolerance to Hymenoptera Venom: A Single Mechanism?

Inducing tolerance in Hymenoptera-allergic patients, bee venom immunotherapy (BVIT) is a widely accepted method to treat severe allergy to bee stings. In order to increase the existing knowledge on the underlying immunological mechanisms and look for possible biomarkers predictive of efficacy, a group of 20 bee-venom-allergic patients (AG) were thoroughly examined during their first year of BVIT. In addition, the results of treated patients with those of an untreated group of 20 tolerant beekeepers (TG) who had previously shown a firm suppressor-regulatory profile were compared. Tolerance in AG patients was invariably associated with a significant regulatory response characterised by the expansion of Helios− subpopulation and increased IL-10, specific IgG4 (sIgG4), and kynurenine levels. Although specific IgE (sIgE) levels increased transiently, surprisingly, the T helper type 2 (Th2) population and IL-4 levels rose significantly after one year of immunotherapy. Thus, the picture of two parallel phenomena emerges: a tolerogenic response and an allergenic one. Comparing these results with those obtained from the TG, different immunological mechanisms appear to govern natural and acquired tolerance to immunotherapy. Of particular interest, the kynurenine levels and T regulatory (Treg) Helios− population could be proposed as new biomarkers of response to BVIT.

Hyper-Immune Bovine Milk as an Immunological and Nutritional Supplement for COVID-19.

Many different strategies have been used to fight against the Coronavirus disease (COVID-19) pandemic as a therapeutics or prophylaxis approaches. However, not enough attention has been paid to general and specific immune factors and nutritional components found in hyper-immunized dairy products. Hyper-immune bovine colostrum (HBC) has been used against many different respiratory and gastrointestinal tracts infections during past decades. An isolated dairy farm was established, and nine mixed Holstein X Simmental dairy cattle in their 6–7 months of gestation period were chosen for hyper-immunization with inactivated Severe acute respiratory syndrome corona virus-2 (SARS-CoV-2). For this, six cows were inoculated with 2 ml of 109.4/ml (TCID50) of the virus. As a control group, three cows were inoculated with the carrier without virus. Specific IgG level against the SARS-CoV-2 was measured before and after immunization in the sera, and in the colostrum and milk following parturition in hyper-immunized cows using indirect Enzyme-linked immunosorbent assay (ELISA). Neutralizing antibodies in the serum and colostrum was measured by a quantitative ELISA. The safety of the product was determined in40 healthy volunteers aged between 18–65 years old (13 females and 27 males) in the phase 1 clinical trial (https://www.irct.ir/trial/51259). No adverse effects were observed in the experimental cows. A very high level of IgG was observed in the first colostrum that sharply decreased in the following 7 days in the milk. The titer of specific neutralizing antibody in the colostrum samples was 69 times higher than the sera. No adverse effects and clinical complications were reported by the authorized ethics committee, and an official certificate on the safety of the product was issued. Beside other strategies, this approach could be used for large-scale and low-cost production of immune components to be used as a nutritional supplement to confront current SARS-CoV-2 and future pandemics.Clinical Trial Registration[https://www.irct.ir/trial/51259].

Screening for Immunodeficiencies in Children With Invasive Pneumococcal Disease: Six-year Experience From a UK Children's Hospital.

A previous study showed that investigation of children with invasive pneumococcal disease (IPD) revealed an immunodeficiency in up to 10% of cases. Following this report, we implemented a protocol to investigate children with IPD, to assess the proportion with an immunodeficiency in our setting. We retrospectively identified patients who presented with IPD from January 2015 to November 2020 and collected data from medical records. Immunological investigations included complement C3 and C4 levels, classical and alternative pathway complement function, IgG, IgA and IgM levels, specific IgG levels (H. influenza B, tetanus and pneumococcal serotypes), peripheral blood film, lymphocyte subsets, and CD62L-shedding upon activation with Toll-like receptor-agonists in selected cases. We identified a total of 68 children with IPD, with a mortality of 6%. Immunological investigations were performed in 51 children. Four children (8%) had abnormal findings that were deemed of clinical significance. Two children had complement deficiencies (Factor I and C2 deficiency), one child had specific antibody deficiency, and another child had low IgM, low NK-cells and poor persistence of serotype-specific anti-pneumococcal IgG concentrations. Of the 17 children with IPD who were not tested for immunodeficiencies, 4 died and four had possible explanations for the infection. We identified clinically relevant abnormal immunological findings in 4/51 (8%) of children with IPD. Our results support the recommendation to perform immunological investigations in children with IPD, since this might reveal underlying immunodeficiencies, allowing for necessary preventive measures and close follow-up.

Production and Evaluation of a Novel Multi-Epitope Bivalent Vaccine Against Echinococcus multilocaularis Metacestode

Alveolar Echinococcosis is a globally widespread zoonotic disease caused by the larval stage of Echinococcus multilocularis (Em) and is seriously harmful to human health. In our previous studies, we found that Em-EMY162 had good prophylactic and therapeutic effects against Em infection and the dominant epitopes of Em-EMY162 and Em-TSP3 were also identified. In this study, a multi-epitope vaccine LTB-ETBM targeting both Em-EMY162 and Em-TSP3 was designed and constructed, and then the immunogenicity and protective efficacy were evaluated in Em infected mice. The results showed that LTB-ETBM could induce high levels of specific IgG against Em-EMY162 and Em-TSP3 and a mixed Th1/Th2 lymphocyte response to LTB-ETBM. Moreover, the LTB-ETBM significantly inhibited the formation of cysts in mice challenged with 1000 Em protoscoleces. In a therapeutic mouse model injected intraperitoneally with 1000 protoscoleces, vaccination with LTB-ETBM using either Freund's or CpG as an adjuvant significantly decreased the growth of protoscoleces and the formation of cysts. LTB-ETBM may be efficacious for use as a prophylactic or therapeutic agent against Em infection.

Динамика гуморального иммунного ответа к SARS-CoV-2 в профессионально однородной группе людей за двухлетний эпидемический период COVID-19

It is important to control the levels of specific IgG against SARS-CoV-2 to ensure the timely monitoring of immunity in patients with COVID-19. Yet it is unclear what antibody levels protect against new infection and how long the protection is maintained. The study was aimed to assess the dynamic changes in the levels of IgG against SARS-CoV-2 by the two-year controlled observation. Healthy individuals (n = 70), COVID-19 survivors (n = 42), and people vaccinated with Sputnik V (n = 43) were enrolled. They were followed-up from April 2020 to April 2022. Serum IgG levels were defined (n = 312) using immunochip and the commercially available test system. Significance of differences was estimated using the Mann–Whitney U test for р ≤ 0.05. IgG levels in the disease survivors (median 97.1; 95% CI: 80–162 BAU/mL) and vaccinated individuals (103.1; 78–139 BAU/mL) were significantly higher than in healthy people (4.3; 4.1–4.5 BAU/mL). Intensity of immune response significantly increased after vaccination of the disease survivors (up to 1023; 657–1191 BAU/mL) or administration of booster dose to vaccinated individuals (413; 213–545 BAU/mL). In elderly convalescents (60+), IgG levels were significantly higher, and in vaccinated people these were significantly lower, than in people under the age of 60. IgG levels decreased faster in vaccinated individuals (after 3–4 months), than in the disease survivors, and stabilized at &lt;100 BAU/mL in 60% of subjects within 5–9 months. Thus, intensity and duration of immune response in COVID-19 survivors and vaccinated people vary significantly depending on age, observation period, and additional vaccinations/revaccinations. Three cases of infection after full vaccination were reported over the entire follow-up period, including infection in a patient having a history of the disease and subsequent vaccination.

Lactobacillus casei Ghosts as a Vehicle for the Delivery of DNA Vaccines Mediate Immune Responses.

We developed Lactobacillus casei bacterial ghosts (BGs) as vehicles for delivering DNA vaccines and analyzed their effects on immune responses. Uptake of the plasmids encoding the enhanced green fluorescent protein (pCI-EGFP) and BGs loaded with pCI-EGFP by macrophages was investigated using fluorescence microscopy and flow cytometry. The results showed that pCI-EGFP-loaded L. casei BGs were efficiently taken up by macrophages. Lactobacillus casei BGs loaded with plasmids encoding VP6 protein of PoRV (pCI-PoRV-VP6) significantly upregulated the mRNA expression of interleukin (IL)-1β, IL-10, tumor necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS), arginase-1 (Arg-1), Mannose receptor (CD206) toll-like receptor (TLR)-2, TLR4, and TLR9 in macrophages. The levels of markers of M1 polarization (IL-10 and TNF-α) and M2 polarization (Arg-1 and CD206) were increased in macrophages incubated with pCI-PoRV-VP6-loaded BGs compared with the control group. The results of the enzyme-linked immunosorbent assay showed that the secretion of IL-1β, IL-10, and TNF-α in macrophages was significantly upregulated compared with the control group. Flow cytometry demonstrated that L. casei BGs loaded with pCI-PoRV-VP6 promoted the maturation of dendritic cells (DCs). Following incubation with pCI-PoRV-VP6-loaded BGs, the mRNA expression levels of IL-1β, IL-6 and interferon (IFN)-γ in DCs were significantly increased. ELISA assay showed the secretion of the IL-1β, IL-6, IFN-γ IL-10 and TNF-α in DCs were upregulated significantly. Thus, L. casei BGs promoted the maturation and activation of DCs. We analyzed the stimulatory capacity of DCs in a mixed lymphocyte reaction with allogeneic T cells. T cell proliferation increased upon incubation with DCs stimulated by BGs. After immunizing mice with BGs loaded with pCI-PoRV-VP6, the specific IgG levels in the serum were higher than those elicited by BGs loaded with pCI-PoRV-VP6. BGs loaded with pCI-PoRV-VP6 on Th1 and Th2 cytokines polarized T cells into the Th1 type and increased the proportion of CD4+/CD8+ T cells. These results indicate L. casei BGs effectively mediate immune responses and can be used as delivery system for DNA vaccination.

IgG Antibody Responses and Immune Persistence of Two Doses of BBIBP-CorV Vaccine or CoronaVac Vaccine in People Living with HIV (PLWH) in Shenzhen, China.

The purpose of this study was to preliminarily evaluate the immunogenicity and immune persistence of inactivated SARS-CoV-2 vaccines in PLWH in the real world. We collected blood samples from 132 PLWH aged 18–59 years who were vaccinated with two doses of BBIBP-CorV vaccine (Sinopharm) or CoronaVac vaccine (SinoVac) at 28 ± 7 days and 180 ± 20 days the after second dose, to detect the level of Spike receptor binding domain-protein specific IgG (S-RBD-IgG) by using chemiluminescence. We found that the BBIBP-CorV vaccine or the CoronaVac vaccine induced lower S-RBD-IgG antibody seropositivity rates and levels in PLWH than in healthy controls (HCs). The BBIBP-CorV vaccine or the CoronaVac vaccine induced lower humoral immune responses in PLWH, having lower CD4+T cell counts (<350 cells/μL) compared to PLWH, and having higher CD4+T cell counts (≥350 cells/μL) after a second dose of vaccination. The BBIBP-CorV vaccine or the CoronaVac vaccine induced lower S-RBD-IgG antibody levels in PLWH, having CD4+T cell counts ≥350 cells/μL compared to HCs. No negative effects were observed in terms of the CD4+T cell counts and HIV RNA viral load (VL) of PLWH after vaccination. Ninety-nine PLWH and eighty-three HCs completed a second blood collection for testing; we found a statistically significant decrease in the humoral immune response both in PLWH and HCs from 28 days to 180 days after a second dose of BBIBP-CorV vaccine or CoronaVac vaccine. The S-RBD-IgG antibody induced by the BBIBP-CorV vaccine or the CoronaVac vaccine declined faster in the PLWH population than in the healthy population, and two doses of the BBIBP-CorV vaccine or the CoronaVac vaccine may not be enough to provide PLWH with persistent immunity against SARS-CoV-2. It is necessary for PLWH to be prioritized for a third dose over the healthy population, but the immunogenicity of the third dose of the homologous or heterologous vaccine requires further study.

Comparison of BNT162b2-, mRNA-1273- and Ad26.COV2.S-Elicited IgG and Neutralizing Titers against SARS-CoV-2 and Its Variants.

Because the vaccine-elicited antibody and neutralizing activity against spike protein of SARS-CoV-2 are associated with protection from COVID-19, it is important to determine the levels of specific IgG and neutralization titers against SARS-CoV-2 elicited by the vaccines. While three widely used vaccine brands (Pfizer-BNT162b2, Moderna-mRNA-1273 and Johnson-Ad26.COV2.S) are effective in preventing SARS-CoV-2 infection and alleviating COVID-19 illness, they have different efficacy against COVID-19. It is unclear whether the differences are due to varying ability of the vaccines to elicit a specific IgG antibody response and neutralization activity against spike protein of the virus. In this study, we compared the plasma IgG and neutralization titers against spike proteins of wild-type SARS-CoV-2 and eight variants in healthy subjects who received the mRNA-1273, BNT162b2 or Ad26.COV2.S vaccine. We demonstrated that subjects vaccinated with Ad26.COV2.S vaccine had significantly lower levels of IgG and neutralizing titers as compared to those who received the mRNA vaccines. While the linear regression analysis showed a positive correlation between IgG levels and neutralizing activities against SARS-CoV-2 WT and the variants, there was an overall reduction in neutralizing titers against the variants in subjects across the three groups. These findings suggest that people who received one dose of Ad26.COV2.S vaccine have a more limited IgG response and lower neutralization activity against SARS-CoV-2 WT and its variants than recipients of the mRNA vaccines. Thus, monitoring the plasma or serum levels of anti-SARS-CoV-2 spike IgG titer and neutralization activity is necessary for the selection of suitable vaccines, vaccine dosage and regimens.

Analysis of immune response in BALB/c mice immunized with recombinant plasmids pMZ-X3-Ts14–3–3.3 and pMZ-X3-sp-Ts14–3–3.3 of Taenia solium

There is a lack of vaccine against human cysticercosis, thus making a huge population at the risk of infection. In this study, we chose a novel potential antigen molecule Taenia solium 14–3–3.3 (Ts14–3–3.3) and optimized it as sp-Ts14–3–3.3 (sp is immunoglobulin H chain V-region precursor, partial) in order to construct recombinant plasmids pMZ-X3-Ts14–3–3.3 and pMZ-X3-sp-Ts14–3–3.3. BALB/c mice were divided into four groups for immunization: pMZ-X3-Ts14–3–3.3, pMZ-X3-sp-Ts14–3–3.3, pMZ-X3 plasmid control group and PBS control group. Compared with two control groups, the proliferation level of splenic lymphocytes increased significantly in pMZ-X3-Ts14–3–3.3 and pMZ-X3-sp-Ts14–3–3.3 groups and reached the maximum in week 6. And the same case arose as cytokines associated with Th1 response, IFN-γ, and IL-2 while those with Th2 response, IL-4, IL-10 went up and reached the maximum in week 4. The levels of serum specific IgG, IgG1 and IgG2a rose and reached the maximum in week 6, 4 and 6, respectively. Meanwhile, the proportion of CD4+/CD8+ splenic T lymphocytes increased and reached the peak in week 6. The results indicated that the recombinant plasmids pMZ-X3-Ts14–3–3.3 and pMZ-X3-sp-Ts14–3–3.3 can induce specific cellular and humoral immune responses in BALB/c mice with immunization. Notably, the recombinant plasmid pMZ-X3-sp-Ts14–3–3.3 has a better immune effect, which proves that Ts14–3–3.3 enjoys a higher possibility as a potential antigen molecule to T. solium vaccine.

Early Cellular and Humoral Responses Developed in Oncohematological Patients after Vaccination with One Dose against COVID-19.

Individuals with oncohematological diseases (OHD) may develop an impaired immune response against vaccines due to the characteristics of the disease or to its treatment. Humoral response against SARS-CoV-2 has been described to be suboptimal in these patients, but the quality and efficiency of the cellular immune response has not been yet completely characterized. In this study, we analyzed the early humoral and cellular immune responses in individuals with different OHD after receiving one dose of an authorized vaccine against SARS-CoV-2. Humoral response, determined by antibodies titers and neutralizing capacity, was overall impaired in individuals with OHD, except for the cohort of chronic myeloid leukemia (CML), which showed higher levels of specific IgGs than healthy donors. Conversely, the specific direct cytotoxic cellular immunity response (DCC) against SARS-CoV-2, appeared to be enhanced, especially in individuals with CML and chronic lymphocytic leukemia (CLL). This increased cellular immune response, developed earlier than in healthy donors, showed a modest cytotoxic activity that was compensated by significantly increased numbers, likely due to the disease or its treatment. The analysis of the immune response through subsequent vaccine doses will help establish the real efficacy of COVID-19 vaccines in individuals with OHD.

Temporary antimetabolite treatment hold boosts SARS-CoV-2 vaccination-specific humoral and cellular immunity in kidney transplant recipients.

Transplant recipients exhibit an impaired protective immunity after SARS-CoV-2 vaccination, potentially caused by mycophenolate (MPA) immunosuppression. Recent data from patients with autoimmune disorders suggest that temporary MPA hold might greatly improve booster vaccination outcomes. We applied a fourth dose of SARS-CoV-2 vaccine to 29 kidney transplant recipients during a temporary (5 weeks) MPA/azathioprine hold, who had not mounted a humoral immune response to previous vaccinations. Seroconversion until day 32 after vaccination was observed in 76% of patients, associated with acquisition of virus-neutralizing capacity. Interestingly, 21/25 (84%) calcineurin inhibitor–treated patients responded, but only 1/4 belatacept-treated patients responded. In line with humoral responses, counts and relative frequencies of spike receptor binding domain–specific (RBD-specific) B cells were markedly increased on day 7 after vaccination, with an increase in RBD-specific CD27++CD38+ plasmablasts. Whereas overall proportions of spike-reactive CD4+ T cells remained unaltered after the fourth dose, frequencies were positively correlated with specific IgG levels. Importantly, antigen-specific proliferating Ki67+ and in vivo–activated programmed cell death 1–positive T cells significantly increased after revaccination during MPA hold, whereas cytokine production and memory differentiation remained unaffected. In summary, antimetabolite hold augmented all arms of immunity during booster vaccination. These data suggest further studies of antimetabolite hold in kidney transplant recipients.

MO836: Patients Receiving Haemodialysis Maintain Sars-Cov-2 Immunity Comparable With Healthy Individuals: A Prospective Cohort Study

Abstract BACKGROUND AND AIMS Patients with end-stage kidney disease receiving maintenance haemodialysis (HD) are at increased risk for mortality after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) compared with the general population. However, it is currently unknown whether the long-term SARS-CoV-2 humoral and cellular immune responses in patients receiving HD are comparable to individuals with normal kidney function. We aimed to investigate the 6-month kinetics of SARS-CoV-2 IgG antibody and specific T-cell levels in patients receiving HD compared with those in healthy individuals. METHOD The prospective cohort study included 24 patients treated with maintenance HD and 27 healthy controls with confirmed history of coronavirus disease (COVID-19). Nobody of them received vaccination before and during the study period. In all participants, the levels of specific IgG were quantified at three timepoints: 10, 18 and 26 weeks from disease onset. In a subgroup of patients, specific CD4+ and CD8+ T-lymphocyte responses were evaluated using IGRA test. RESULTS The incidence of COVID-19-related symptoms did not differ between the groups, except for the loss of smell, which occurred much more frequently among healthy subjects (70% versus 30.4% in HD group, P = 0.01). The seropositivity rate declined in healthy subjects over time and was 85% and 70.4% at weeks 18 and 26, respectively. All HD patients remained seropositive over the study period. Seropositivity rate at week 26 was greater among patients receiving HD: RR = 1.4 [95% confidence interval (95% CI): 1.17–1.94] (reciprocal of RR = 0.7, 95% CI: 0.52–0.86), P = 0.0064. In both groups, IgG levels decreased from week 10 to week 26, but antibodies vanished more rapidly in controls than in HD group (ANOVA P = 0.0012)—Figure 1. The magnitude of T-cell response was significantly lower in controls than in HD patients at weeks 10 (P = 0.019) and 26 (P = 0.0098) after COVID-19 diagnosis, but not at week 18—Figure 2. CONCLUSION Compared with healthy adults, patients receiving HD maintain significant long-term humoral and cellular immune responses following natural COVID-19. SARS-CoV-2 IgG antibodies did not decline more rapidly in patients receiving HD than in healthy controls over 6-months period.

MO856: Immunogenicity and Adverse Events After Vaccination With GAM-COVID-VAC (Sputnik V) in Patients on Maintenance Haemodialysis Compared With Healthy Controls: A Preliminary Report

Abstract BACKGROUND AND AIMS Recent studies evaluated safety and efficacy of vaccines against coronavirus disease (COVID-19), but none of them are currently approved in Russia. Here, we report results on immunogenicity of the recombinant adenovirus (rAd) 26 and rAd5 vector-based COVID-19 vaccine Gam-COVID-Vac (Sputnik V, developed by Gamaleya National Research Centre, Russia) in patients, receiving maintenance haemodialysis (HD). We aimed to compare the strength of humoral and cellular immunity after 2 doses of Gam-COVID-Vac in patients receiving HD and individuals with normal kidney function. METHOD The prospective cohort study (NCT: 04 805 632) included 23 patients treated with maintenance HD and 28 volunteers with normal kidney function. All participates were adult, had been fully vaccinated with Gam-COVID-Vac vaccine and had no prior history of suspected or confirmed COVID-19. Subjects were excluded if they had a history of confirmed SARS-CoV-2 infection, had underlying autoimmune disease, malignancies or concomitant immunosuppressive therapy. In all participants the levels of specific IgG were quantified at 4 weeks after second vaccine dose administration using a semi-quantitative SARS-CoV-2 S1 IgG enzyme-linked immunosorbent assay. In all subjects, specific CD4+ and CD8+ T-lymphocyte responses (count of spots to spike structural peptide of SARS-CoV-2 virus in IGRA test) were evaluated at the same timepoint. All the participants were asked to report adverse events (AEs) following first and second vaccine administration, included general malaise, fever, myalgia, headache, allergic reactions and injection site reactions. RESULTS Overall, the incidence of vaccine-associated AEs was less in HD patients than in healthy controls: 32% versus 75% after both first and second vaccine administrations, RR = 0.46 (95% confidence interval 0.24–0.79), P = 009 (Table 1). The most commonly reported AE in both groups was pain in the injection site. No severe or serious AEs occurred in both patients and healthy controls. The seroconversion rate in 4 weeks after second vaccine shot reached 100% (28 of 28) in healthy subjects and 87% (20 of 23) in patients receiving HD. IgG levels did not differ between groups: 4.7 [Q1-Q3: 3.37; 6.25] in HD patients versus 5.5 [Q1-Q3: 3.3; 7.2] in controls, P = 0.219 (Figure 1A). The T-test result was positive in 70% (16 of 23) of HD patients and in 79% (22 of 28) of controls. The magnitude of T-cell response was comparable between groups: 30 spots [Q1-Q3: 11; 48] in HD patients versus 30 spots [Q1-Q3: 14; 51] in controls, P = 0.745 (Figure 1B). CONCLUSION Patients receiving HD develop efficient humoral and cellular immune responses after complete vaccination against COVID-19 with Gam-COVID-Vac vaccine, which is comparable with those in healthy adults.

Features of the humoral response to immunization "Gam-COVID-Vac" and in patients with COVID-19

The paper present the results of a survey of people who have undergone immunization with a combined vector vaccine for the prevention of coronavirus infection COVID-19 «Sputnik V - Gam-COVID-Vac», as well as COVID-19 recovalents. Using a quantitative enzyme-linked immunosorbent assay, the levels of specific IgG were determined in persons who had had different degrees of severity before vaccination, in persons who were immuno-negative before immunization, as well as in convalescents who had undergone coronavirus infection of varying severity. The immunological targeting of antibodies against various SARS-CoV-2 proteins is considered.

Immunoglobulin G passive transfer from mothers to infants: total IgG, IgG subclasses and specific antipneumococcal IgG in 6-week Malawian infants exposed or unexposed to HIV

BackgroundThe impaired transplacental passage of IgG from mothers living with HIV to their infants could be one of the causes of the high vulnerability to infections of HIV-exposed uninfected (HEU) infants, but controversial results have been obtained in different settings. The aim of this study was to assess in 6-week old HEU and HIV-unexposed, uninfected (HUU) Malawian infants the total IgG levels, the subclasses profile and the concentrations of global anti-pneumococcal capsular polysaccharide (anti-PCP) IgG and IgG2.MethodsDried blood spots were collected from 80 infants (40 HEU, 40 HUU) and antibodies concentrations determined by nephelometric method (total IgG and subclasses), or using ELISA (anti-PCP total IgG and IgG2). Results are expressed as median levels with IQR, while the proportions of each subclass out of the total IgG are used to describe the subclasses profile.ResultsAt 6 weeks HEU infants had higher median levels of total IgG and IgG1 and a significantly lower level of IgG2 [0.376 (0.344–0.523) g/l vs 0.485 (0.374–0.781) g/l, p = 0.037] compared to the HUU counterparts. The IgG subclasses distribution confirmed the underrepresentation of IgG2 (IgG2 represented 5.82% of total IgG in HEU and 8.87% in HUU). The anti-PCP IgG and IgG2 levels were significantly lower in HEU infants [8.9 (5.4–15.1) mg/l vs 16.2 (9.61–25.8) mg/l in HUU, p < 0.001, and 2.69 (1.90–4.29) mg/l vs 4.47 (2.96–5.71) mg/l in HUU, p = 0.001, respectively].ConclusionCompared to HUU infants, HEU infants have IgG abnormalities mainly represented by low IgG2 levels, suggesting that despite maternal antiretroviral therapy, the mechanisms of IgG transplacental passage continue to be impaired in women living with HIV. HEU infants also showed a significantly lower level of specific anti-PCP IgG, possibly favouring a high vulnerability to S. pneumoniae infection at an age when protection is mostly depending on maternal IgG.

TTV Load is Associated with SARS-CoV-2 Vaccination Response in Lung Transplant Recipients

PurposeAlthough the currently approved COVID-19 vaccines are highly effective, SARS-CoV-2-specific immune responses are diminished in lung transplant recipients (LTR), probably due to immunosuppression (IS). There is currently no marker of IS that can be used to predict vaccination responses. Here, we study if torque tenovirus (TTV) can be used as a predictive marker.MethodsThe humoral response to the mRNA-1273 vaccine was assessed in 103 LTR, who were vaccinated 4 to 237 months after Lung transplantation. Spike (S)-specific IgG levels were measured at baseline, 28 days after first, and 28 days after the second vaccination. TTV loads were determined by RT-PCR and Pearson's correlation coefficient was calculated to correlate serological responses to TTV load.ResultsHumoral responses to the vaccine COVID-19 vaccination were found in 41/103 (40%) LTR at 28 days after the second vaccination. 62 /103 (60%) had no detectable antibodies. TTV loads at baseline correlated with S-specific antibodies and the percentage of responders (=<0.001) (Fig 1). TTV loads also strongly correlated with the time since transplantation, indicating that participants with lower TTV loads were longer after transplantation.ConclusionThis study shows an association between baseline TTV load and mRNA-1273-induced S-specific antibodies. If the TTV load is indeed a predictor of vaccination responses, this can be used in the future as a potential guidance for optimizing vaccination regimens. Therefore, we recommend that TTV load measurements are included in further vaccination efficacy studies in immunocompromised cohorts.

High torque tenovirus (TTV) load before first vaccine dose is associated with poor serological response to COVID-19 vaccination in lung transplant recipients.

BackgroundSerological responses to COVID-19 vaccination are diminished in recipients of solid organ transplants, especially in lung transplant recipients (LTR), probably as result of immunosuppressive treatment. There is currently no marker of immunosuppression that can be used to predict the COVID-19 vaccination response. Here, we study whether torque tenovirus (TTV), a highly prevalent virus can be used as an indicator of immunosuppression.MethodsThe humoral response to the mRNA 1273 vaccine was assessed in 103 LTR, who received a transplant between 4 and 237 months prior to vaccination, by measuring Spike (S)-specific IgG levels at baseline, 28 days after first, and 28 days after the second vaccination. TTV loads were determined by RT-PCR and Pearson's correlation coefficient was calculated to correlate serological responses to TTV load.ResultsHumoral responses to COVID-19 vaccination were observed in 41 of 103 (40%) LTR at 28 days after the second vaccination. Sixty-two of 103 (60%) were non-responders. Lower TTV loads at baseline (significantly) correlated with higher S-specific antibodies and a higher percentage of responders. Lower TTV loads also strongly correlated with longer time since transplantation, indicating that participants with lower TTV loads were longer after transplantation.ConclusionsThis study shows a better humoral response to the SARS-CoV-2 vaccine in subjects with a lower TTV load pre-vaccination. In addition, TTV load correlates with the time after transplantation. Further studies on the use of TTV load in vaccination efficacy studies in immunocompromised cohorts should provide leads for the potential use of this marker for optimizing vaccination response.