Waning of Anti-Spike IgG Antibody Titer after COVID-19 Vaccination: Myth or Reality?

This observational prospective study was conducted on 25 patients who had received a full 3-dose COVID-19 vaccination scheme with a follow-up ranging from 12 to 19 months after the last injection. The aim of the study was focused on a single biological indicator the anti-spike IgG antibody titer. The age of the patients ranged from 51 to 85 years old. 15 out 25 patients (60%) presented a comorbidity. Our data showed a persistent positive anti-spike IgG antibodies titer ranging from 105 to 5680 BAU/mL (mean: 2661 BAU/mL) in all patients. In view of these results, systematic administration of a SARS-CoV-2 vaccine booster is questionable and should be individually tailored according to the patient medical condition and the anti-spike IgG antibody level.

Anti- MSP-1_(19) antibody (IgG) and reactive oxygen species (ROS) response against malaria infection in pregnancy in South Western Nigeria

Objective:Although immunity to malaria is reduced in pregnancy,the maternal immune system still continues to respond to malaria infection by the production of antibodies.IgG has been reported to play significant role in immune response against P.falciparum.Anti-MSP-1_(19) antibody and reactive oxygen species have been shown to be protective against malaria infection in children.This work assessed the response of anti-MSP-1_(19) antibody(a promising blood stage vaccine candidate antigen) and oxidative stress in 250 pregnant women.Methods: Blood samples were collected in dry and wet seasons.Plasmodium falciparum infection was determined by microscopy, anti-MSP-1_(19) IgG level was investigated using ELISA.Malondiadelhyde(MDA) and reduced glutathione (GSH) were used as indicators of oxidative stress and they were quantified spectrophotometrically.Results: Parasitaemia was significantly higher(P<0.05) in wet than dry season and its level decreased with gravidity.There was a significant increase(P<0.05) in anti-MSP-1_(19) IgG and MDA levels in the dry than wet season.Anti-MSP-1_(19) IgG and MDA levels were significantly higher in P.falciparum positive primigravidae than P.falciparum negative primigravidae in both wet and dry seasons.In wet season anti-MSP-1_(19) IgG level was significantly increased(P<0.05) in P.falciparum positive multigravidae than P.falciparum negative. The anti-MSP-1_(19) IgG and MDA were significant higher in P.falciparum positive multigravidae than primigravidae. Reduced glutathione(GSH) level was significantly reduced(P<0.05) among malaria positive than malaria negative patients in both seasons.Conclusion:This study suggests that IgG and MDA response were positively associated with the presence of malaria infection.

Human IgM and IgG Responses to an Inactivated SARS-CoV-2 Vaccine

Objective:The ongoing COVID-19 pandemic warrants accelerated efforts to test vaccine candidates.To explore the influencing factors on vaccine-induced effects,antibody responses to an inactivated SARS-CoV-2 vaccine in healthy individuals who were not previously infected by COVID-19 were assessed.Methods:All subjects aged 18-60 years who did not have SARS-CoV-2 infection at the time of screening from June 19,2021,to July 02,2021,were approached for inclusion.All participants received two doses of inactivated SARS-CoV-2 vaccine.Serum IgM and IgG antibodies were detected using a commercial kit after the second dose of vaccination.A positive result was defined as 10 AU/mL or more and a negative result as less than 10 AU/mL.This retrospective study included 97 infection-naive individuals(mean age 35.6 years;37.1%male,62.9%female).Results:The seropositive rates of IgM and IgG antibody responses elicited after the second dose of inactivated SARS-CoV-2 vaccine were 3.1%and 74.2%,respectively.IgG antibody levels were significantly higher than IgM levels(P<0.0001).Sex had no effect on IgM and IgG antibody response after the second dose.The mean anti-IgG level in older persons(≥42 years)was significantly lower than that of younger recipients.There was a significantly lower antibody level at>42 days compared to that at 0-20 days(P<0.05)and 21-31 days(P<0.05)after the second dose.Conclusion:IgG antibody response could be induced by inactivated SARS-CoV-2 vaccine in healthy individuals(>18 years),which can be influenced by age and detection time after the second dose of vaccination.

Postoperative change of anti-Thomsen-Friedenreich and Tn IgG level: The follow-up study of gastrointestinal cancer patients

AIM: To study the influence of tumor removal on the serum level of IgG antibodies to tumor-associated Thomsen-Friedenreich (TF), Tn carbohydrate epitopes and xenogeneic αGal, and to elucidate on the change of the level during the follow-up as well as its association with the stage and morphology of the tumor and the values of blood parameters in gastrointestinal cancer. METHODS: Sixty patients with gastric cancer and 34 patients with colorectal cancer in stages Ⅰ-Ⅳ without distant metastases were subjected to follow- up. The level of antibodies in serum was determined by the enzyme-linked immunosorbent assay (ELISA) using synthetic polyacrylamide (PAA) glycoconjugates. Biochemical and haematological analyses were performed using automated equipment. RESULTS: In gastrointestinal cancer, the TF antibody level was found to have elevated significantly after the removal of G3 tumors as compared with the preoperative level (u = 278.5, P < 0.05). After surgery, the TF and Tn antibody level was elevated in the majority of gastric cancer patients (sign test, 20 vs 8, P < 0.05, and 21 vs 8, P < 0.05, respectively). In gastrointestinal cancer, the elevated postoperative level of TF, Tn and αGal antibodies was noted in most patients with G3 tumors (sign test, 22 vs 5, P < 0.01; 19 vs 6, P < 0.05; 24 vs 8, P < 0.01, respectively), but the elevation was not significant in patients with G1 + G2 resected tumors. The postoperative follow-up showed that the percentage of patients with G3 resected tumors of the digestive tract, who had a mean level of anti-TF IgG above the cut- off value (1.53), was significantly higher than that of patients with G1 + G2 resected tumors (χ2 = 3.89, all patients; χ2 = 5.34, patients without regional lymph node metastases; P < 0.05). The percentage of patients with a tumor in stage I, whose mean anti-TF IgG level remained above the cut-off value (1.26), was significantly higher than that of patients with the cancer in stages Ⅲ-Ⅳ (χ2 = 4.71, gastric cancer; χ2 = 4.11, gastrointestinal cancer; P < 0.05). The correlation was observed to exist between the level of anti-TF IgG and the count of lymphocytes (r = 0.517, P < 0.01), as well as between the level of anti- Tn IgG and that of serum CA 19-9 (r = 0.481, P < 0.05). No positive delayed-type hypersensitivity reaction in skin test challenges with TF-PAA in any of the fifteen patients, including those with a high level of anti-TF IgG, was observed. CONCLUSION: The surgical operation raises the level of anti-carbohydrate IgG in most patients, especially in those with the G3 tumor of the gastrointestinal tract. The follow-up demonstrates that after surgery the low preoperative level of TF antibodies may be considerably increased in patients with the carcinoma in its early stage but remains low in its terminal stages. The stage- and morphology-dependent immunosuppression affects the TF-antibody response and may be one of the reasons for unresponsiveness to the immunization with TF-antigens.

Universal chimeric Fcγreceptor T cells with appropriate affinity for IgG1 antibody exhibit optimal antitumor efficacy

Developing universal CARs with improved flexible targeting and controllable activities is urgently needed.While several studies have suggested the potential of CD16a in tandem with monoclonal antibodies to construct universal CAR-T cells,the weak affinity between them is one of the limiting factors for efficacy.Herein,we systematically investigated the impact of Fcγreceptor(FcγR)affinity on CAR-T cells properties by constructing universal CARs using Fcγreceptors with different affinities for IgG1 antibodies,namely CD16a,CD32a,and CD64.We demonstrated that the activities of these universal CAR-T cells on tumor cells could be redirected and regulated by IgG1 antibodies.In xenografted mice,64CAR chimeric Jurkat cells with the highest affinity showed significant antitumor effects in combination with herceptin in the HER2 low expression U251 MG model.However,in the CD20 high expression Raji model,64CAR caused excessive activation of CAR-T cells,which resulted in cytokine release syndrome(CRS)and the decline of antitumor activity,and 32CAR with a moderate affinity brought the best efficacy.Our work extended the knowledge about FcγR-based universal CAR-T cells and suggested that only the FcγRCAR with an appropriate affinity can offer the optimal antitumor advantages of CAR-T cells.

Seroprevalence of SARS-CoV-2 among Blood Donors in the Republic of Congo

Corona Virus Disease 2019 (COVID-19) is a highly transmissible and pathogenic viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which erupted in Wuhan, China, in 2019 and has spread worldwide [1]. The objective of this study was to assess the seroprevalence of SARS-CoV-2 among blood donors in the Republic of Congo. Method: This is an analytical and cross-sectional study that was carried out during the period from July to December 2021. Biological analyses were performed with the serological tests n2019 rapid IgG/IgM from Beijing Diagreat Biotechnologies and antigen tests from Abbot using the serum for the detection of anti-SARS-Cov-2 antibodies and nasal mucus for the detection of SARS-Cov-2 antigens. Statistical analysis was performed using SPSS version 22. The Results: Out of 2553 donors recruited in our study, we observed a predominance of male sex with 86.1% or a ratio of 6.19, the age group of 18 - 30 years was dominant with 45.9%, family donation represented 59.2%, the dominant profession was workers with 46.9% and the dominant blood group was O Rh positive with 54%. The prevalence of anti-SRAS-CoV-2 antibodies and antigens were respectively 31.4% for anti-SRAS CoV-2 IgG antibodies, 36.7% for anti-SRAS CoV-2 IgM antibodies and 2.93% for SARS-CoV-2 antigen.

Evaluation of the Therapeutic Potential of Warburgia ugandensis,Prunus africana,and Piliostigma thonningii against Leishmania donovani in vitro and in Balb/c Mice

Leishmaniasis is a zoonotic disease caused by protozoan parasites of the genus Leishmania.Conventional chemotherapy remains to be the most preferred measure against leishmaniasis despite being associated with high toxicity and relapse rates.They are also expensive and require hospitalization.Plant-based compounds provide a better treatment alternative because they are effective,cheap,and less associated with toxicity and resistance.This study examined the therapeutic potential of Warburgia ugandensis,Prunus africana,and Piliostigma thonningii against Leishmania donovani infection in BALB/c mice.Anti-promastigote and toxicity studies were evaluated by incubating the test compound with promastigotes and Vero cells,respectively.Serum was obtained from the mice for total immunoglobulin gamma(IgG)quantification.For in vivo studies,the mice were infected with virulent Leishmania donovani then treated with methanolic extracts of Warburgia ugandensis,Prunus africana,and Piliostigma thonningii and control drug,pentostam(sodium stibogluconate).Treatment with the plant extracts and standard drug resulted to significant reduction in parasite burden.Outcomes in the mice treated with plant extracts were comparable to those treated with pentostam(P≥0.05).In the promastigote assay,all the test compounds killed more than half of the promastigotes at the highest concentration(500μg/mL).Warburgia ugandensis,P.thonningii,and P.africana reduced the number of promastigotes from 2.0×10^(6) to 7.7×10^(3),72.0×10^(3),and 5.0×10^(3),respectively.Pentostam had the lowest IC50(210μg/mL),followed by Warburgia ugandensis(IC50 of 270μg/mL).Piliostigma thonningii and P.africana were less toxic with IC50 of 720μg/mL and 500μg/mL,respectively.There was low production of IgG antibodies following treatment with the plant extracts and high levels in the untreated control.

INFLUENCE OF IRON DEFICIENCY ON SERUM IgG SUBCLASS AND PNEUMOCOCCAL POLYSACCHARIDES SPECIFIC IgG SUBCLASS ANTIBODIES

The serum IgG subclass concentrations in 47 cases and specific IgG subclass antibodies against pneumococcal polysaccharides (PnPs) were measured in 18 cases with iron deficiency. IgG subclass deficiencies were found in 28 (59.6%) cases with the frequency in order as IgG4 (27.7%, 13 / 47), IgGl (21.3%, 10/47), IgG3 (14.9%, 7/47), and IgG2 (2.1%, 1 / 47). Compared with age-atched healthy children, the mean concentration of serum IgG4 and IgGl, and PnPs specific IgGl, IgG2 antibodies were decreased in children with iron deficiency. Decreased CD4 cells and CD4 / CD8 ratio in peripheral blood, low interleukin? (IL-6) activity, reduced lymphocyte proliferative responsiveness and increased recurrent respiratory tract infections (RRTI) were found in iron deticiency children. These results suggested that serum IgG subclass and PnPs specific IgG subclass antibody deficiencies caused by dysfunction of the regulation of T lymphocyte on B lymphocyte may be related to the susceptibility to RRTI in children with iron deficiency.

Infection with severe fever with thrombocytopenia virus in healthy population:a cohort study in a high endemic region,China

Background: Severe fever with thrombocytopenia (SFTS) caused by SFTS virus (SFTSV) was a tick-borne hemorrhagic fever that posed significant threat to human health in Eastern Asia. The study was designed to measure the seroprevalence of SFTSV antibody in healthy population residing in a high endemic region.Methods: A cohort study was performed on healthy residents in Shangcheng County in Xinyang City from April to December in 2018, where the highest SFTS incidence in China was reported. Anti-SFTSV IgG was measured by indirect enzyme-linked immunosorbent assay and neutralizing antibody (NAb) was detected by using PRNT50. The logistic regression models were performed to analyze the variables that were associated with seropositive rates.Results: Totally 886 individuals were recruited. The baseline seroprevalence that was tested before the epidemic season was 11.9% (70/587) for IgG and 6.8% (40/587) for NAb, which was increased to 13.4% (47/350) and 7.7% (27/350) during the epidemic season, and further to 15.8% (80/508) and 9.8% (50/508) post epidemic. The IgG antibody-based seropositivity was significantly related to the patients aged ≥ 70 years old [adjusted odds ratio (OR) = 2.440, 95% confidence interval (CI): 1.334-4.461 compared to the group of < 50 years old,P = 0.004], recent contact with cats (adjustedOR = 2.195, 95%CI: 1.261-3.818,P = 0.005), and working in tea garden (adjustedOR = 1.698, 95%CI: 1.002-2.880,P = 0.049) by applying multivariate logistic regression model. The NAb based seropositivity was similarly related to the patients aged ≥ 70 years old (adjustedOR = 2.691, 95%CI: 1.271-5.695 compared to the group of < 50 years old,P = 0.010), and recent contact with cats (OR = 2.648, 95%CI: 1.419-4.941,P = 0.002). For a cohort of individuals continually sampled with 1-year apart, the anti-SFTSV IgG were maintained at a stable level, while the NAb level reduced.Conclusions: Subclinical infection might not provide adequate immunity to protect reinfection of SFTSV, thus highlighting the ongoing threats of SFTS in endemic regions, which called for an imperative need for vaccine development. Identification of risk factors might help to target high-risk population for public health education and vaccination in the future.

Highly sensitive,scalable,and rapid SARS-CoV-2 biosensor based on In_(2)O_(3)nanoribbon transistors and phosphatase

Developing convenient and accurate SARS-CoV-2 antigen test and serology test is crucial in curbing the global COVID-19 pandemic.In this work,we report an improved indium oxide(In2O3)nanoribbon field-effect transistor(FET)biosensor platform detecting both SARS-CoV-2 antigen and antibody.Our FET biosensors,which were fabricated using a scalable and cost-efficient lithography-free process utilizing shadow masks,consist of an In_(2)O_(3)channel and a newly developed stable enzyme reporter.During the biosensing process,the phosphatase enzymatic reaction generated pH change of the solution,which was then detected and converted to electrical signal by our In_(2)O_(3)FETs.The biosensors applied phosphatase as enzyme reporter,which has a much better stability than the widely used urease in FET based biosensors.As proof-of-principle studies,we demonstrate the detection of SARS-CoV-2 spike protein in both phosphate-buffered saline(PBS)buffer and universal transport medium(UTM)(limit of detection[LoD]:100 fg/mL).Following the SARS-CoV-2 antigen tests,we developed and characterized additional sensors aimed at SARS-CoV-2 IgG antibodies,which is important to trace past infection and vaccination.Our spike protein IgG antibody tests exhibit excellent detection limits in both PBS and human whole blood((LoD):1 pg/mL).Our biosensors display similar detection performance in different mediums,demonstrating that our biosensor approach is not limited by Debye screening from salts and can selectively detect biomarkers in physiological fluids.The newly selected enzyme for our platform performs much better performance and longer shelf life which will lead our biosensor platform to be capable for real clinical diagnosis usage.

Misdiagnostic analysis of clinically diagnosed severe acute respiratory syndrome after following up 197 convalescent patients

The severe acute respiratory syndrome （SARS） is an emerging and highly contagious infection caused by a newly discovered strain of coronavirus. Since the clinical case definition of SARS is similar to other severe atypical pneumonias, specific laboratory tests that can accurately diagnose SARS-associated coronavirus （SARS-CoV） infection are important. However, published data are insufficient to investigate whether clinically diagnosed SARS patients may include some non-SARS pneumonia. Therefore, we aimed to determine clinical and laboratory features to differentiate SARS patients from non-SARS pneumonias that could reduce misdiagnosis of SARS. A retrospective analysis of clinical and laboratory characteristics after the initial onset of SARS, as well as its convalescent-phase, was examined from clinically diagnosed 197 SARS patients.

Evaluating seroprevalence to circumsporozoite protein to estimate exposure to three species of Plasmodium in the Brazilian Amazon

Background:Brazil has seen a great decline in malaria and the country is moving towards elimination.However,for eventual elimination,the control program needs efficient tools in order to monitor malaria exposure and transmission.In this study,we aimed to evaluate whether seroprevalence to the circumsporozoite protein(CSP)is a good tool for monitoring the exposure to and/or evaluating the burden and distribution of Plasmodium species in the Brazilian Amazon.Methods:Cross-sectional surveys were conducted in a rural area of Porto Velho,Rondônia state.Parasite infection was detected by microscopy and polymerase chain reaction.Antibodies to the sporozoite CSP repeats of Plasmodium vivax,P.falciparum,and P.malariae(PvCS,PfCS,and PmCS)were detected using the enzyme-linked immunosorbent assay technique.Human leukocyte antigen(HLA)-DRB1 and DQB1 genes were typed using Luminex®xMAP®technology.Results:The prevalence of immunoglobulin G against P.vivax CSP peptide(62%)was higher than P.falciparum(49%)and P.malariae(46%)CSP peptide.Most of the studied individuals had antibodies to at least one of the three peptides(72%),34%had antibodies to all three peptides and 28%were non-responders.Although the majority of the population was not infected at the time of the survey,74.3%of parasite-negative individuals had antibodies to at least one of the CSPs.Importantly,among individuals carrying the haplotypes DRB1*04~DQB1*03,there was a significantly higher frequency of PfCS responders,and DRB1*16~DQB1*03 haplotype for PvCS and PfCS responders.In contrast,HLA-DRB1*01 and HLA-DQB1*05 allelic groups were associated with a lack of antibodies to P.vivax and P.falciparum CSP repeats,and the haplotype DRB1*01~DQB1*05 was also associated with non-responders,including non-responders to P.malariae.Conclusions:Our results show that in low transmission settings,naturally acquired antibody responses against the CSP repeats of P.vivax,P.falciparum,and P.malariae in a single cross-sectional study may not represent a valuable marker for monitoring recent malaria exposure,especially in an area with a high prevalence of P.vivax.Furthermore,HLA class II molecules play an important role in antibody response and require further study with a larger sample size.It will be of interest to consider HLA analysis when using serosurveillance to monitor malaria exposure among genetically diverse populations.

A COVID-19 Patient Discharged According to Strict Discharge Standards:Viral Negativity in Both Nasopharynx and Feces

Severe acute respiratory syndrome Coronavirus 2(SARS-CoV-2)currently has spread all over the world.However,the dynamic characteristics of SARS-CoV-2 infections have not previously been described in detail.Here,we report a cured patient in West China Hospital,and describe the dynamic detection of SARS-CoV-2-RNA in different specimens and viral specific IgM and IgG antibodies in blood.The findings suggest that the fecal SARS-CoV-2-RNA negativity may be considered as a new standard for de isolation.Serum IgM and IgG antibodies detection were helpful for early diagnosis of SARS-CoV-2 infection and judgment of patients in recovery stage,respectively.