Higher IgG Levels Research Articles

The serological immunogenicity of the third and fourth doses of COVID-19 vaccine in patients with inflammatory rheumatic diseases on different biologic or targeted DMARDs: a Swedish nationwide study (COVID-19-REUMA).

Results from this study provide further evidence that additional doses of COVID-19 vaccines are immunogenic and result in satisfactory antibody response in a majority of patients with inflammatory rheumatic diseases (IRD) receiving potent immunomodulating treatments such as biological or targeted disease-modifying anti-rheumatic drugs (DMARDs) given as monotherapy or combined with traditional DMARDs. We observed that rituximab treatment, both as monotherapy and combined with csDMARDs, impaired antibody response, and only roughly 50% of patients developed a satisfactory antibody response including response to omicron subvariants after the third vaccine. In addition, higher IgG levels at the last rituximab course before the third vaccine dose and a longer time after the last rituximab treatment increased the chance of a satisfactory antibody response. These results indicate that rituximab-treated patients should be prioritized for additional vaccine doses. EudraCT (European Union Drug Regulating Authorities Clinical Trials Database) with number 2021-000880-63.

A subunit-based influenza/SARS-CoV-2 Omicron combined vaccine induced potent protective immunity in BALB/c mice.

Infection with influenza A virus (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a significant risk to human life, health, and the global economy. Vaccination is one of the most effective strategies in the fight against infectious viruses. In this study, we, for the first time, have evaluated the immunogenicity and protective effect of an influenza/SARS-CoV-2 Omicron subunit combined vaccine adjuvanted with MF59 and administered to BALB/c mice. Results showed that the combined vaccine induced high levels of IgG, IgG1 , and IgG2a antibodies, as well as influenza A H1N1/California/2009 virus-specific hemagglutination-inhibiting antibodies in BALB/c mice. Moreover, this subunit combined vaccine induced high titers of neutralization antibodies against SARS-CoV-2 Omicron sublineage BA.5 pseudovirus and effectively reduced the viral load of authentic SARS-CoV-2 Omicron sublineage BA.5.2 in the cell culture supernatants. These results suggested that this subunit combined vaccine achieved protective effect against both H1N1 A/California/07/2009 strain and SARS-CoV-2 Omicron BA.5.2 variant. It is therefore expected that this study will establish the scientific foundation for the next-step development of combined vaccines against other strains or variants of IAV and SARS-CoV-2.

Inhalable hybrid nanovaccines with virus-biomimetic structure boost protective immune responses against SARS-CoV-2 variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with different antigenic variants, has posed a significant threat to public health. It is urgent to develop inhalable vaccines, instead of injectable vaccines, to elicit mucosal immunity against respiratory viral infections. We reported an inhalable hybrid nanovaccine (NVRBD-MLipo) to boost protective immunity against SARS-CoV-2 infection. Nanovesicles derived from genetically engineered 293T cells expressing RBD (NVRBD) were fused with pulmonary surfactant (PS)-biomimetic liposomes containing MPLA (MLipo) to yield NVRBD-MLipo, which possessed virus-biomimetic structure, inherited RBD expression and versatile properties. In contrast to subcutaneous vaccination, NVRBD-MLipo, via inhalable vaccination, could efficiently enter the alveolar macrophages (AMs) to elicit AMs activation through MPLA-activated TLR4/NF-κB signaling pathway. Moreover, NVRBD-MLipo induced T and B cells activation, and high level of RBD-specific IgG and secretory IgA (sIgA), thus elevating protective mucosal and systemic immune responses, while reducing side effects. NVRBD-MLipo also demonstrated broad-spectrum neutralization activity against SARS-CoV-2 (WT, Delta, Omicron) pseudovirus, and protected immunized mice against WT pseudovirus infection. This inhalable NVRBD-MLipo, as an effective and safe nanovaccine, holds huge potential to provoke robust mucosal immunity, and might be a promising vaccine candidate to combat respiratory infectious diseases, including COVID-19 and influenza.

Semiquantitative 18F-FDG PET/CT in monitoring glucocorticoid response of immunoglobulin G4-related effusive constrictive pericarditis: a case report

BackgroundImmunoglobulin G4 (IgG4)-related effusive constrictive pericarditis (ECP) is a rare manifestation of IgG4-related disease (IgG4-RD). It can lead to persistent pericardial fibrosis, resulting in cardiac tamponade, diastolic dysfunction, and heart failure. Glucocorticoids are the primary treatment for effectively reducing inflammation and preventing fibrosis. However, guidelines for monitoring treatment response are lacking and tapering glucocorticoid therapy for specific target organs remains a challenge. Recent studies on IgG4-RD have demonstrated that semiquantitative measurements of fluorine-18 fluorodeoxyglucose (18F-FDG) uptake in the main involved organs in positron emission tomography/computed tomography (PET/CT) scanning are correlated to disease activity. We present a case of IgG4-related ECP to demonstrate the usefulness of 18F-FDG PET/CT for diagnosing and treatment follow-up of IgG4-related ECP.Case presentationHerein, a 66-year-old woman diagnosed with IgG4-related ECP presented with breathlessness, leg swelling, rales, and fever. Laboratory tests revealed markedly elevated levels of C-reactive protein, and transthoracic echocardiography revealed constrictive physiology with effusion. High IgG4 levels suggested an immune-related pathogenesis, while viral and malignant causes were excluded. Subsequent pericardial biopsy revealed lymphocyte and plasma cell infiltration in the pericardium, confirming the diagnosis of IgG4-related ECP. 18F-FDG PET/CT revealed increased uptake of 18F-FDG in the pericardium, indicating isolated cardiac involvement of IgG4-RD. Treatment with prednisolone and colchicine led to a rapid improvement in the patient’s condition within a few weeks. Follow-up imaging with 18F-FDG PET/CT after 3 months revealed reduced inflammation and improved constrictive physiology on echocardiography, leading to successful tapering of the prednisolone dose and discontinuation of colchicine.ConclusionThe rarity of IgG4-related ECP and possibility of multiorgan involvement in IgG4-RD necessitates a comprehensive diagnostic approach and personalized management. This case report highlights the usefulness of 18F-FDG PET/CT in the diagnosis and treatment follow-up of isolated pericardial involvement in IgG4-RD.

Diagnostic challenges of the idiopathic plasmacytic lymphadenopathy (IPL) subtype of idiopathic multicentric Castleman disease (iMCD): Factors to differentiate from IgG4-related disease

Aims and methodsIdiopathic multicentric Castleman disease (iMCD) is currently considered to be classified into three clinical subtypes, including idiopathic plasmacytic lymphadenopathy (IPL), thrombocytopaenia, anasarca, fever, reticulin fibrosis/renal dysfunction, organomegaly (TAFRO)...

Predictive roles of NETs and IgG in neoadjuvant chemotherapy for muscle-invasive bladder cancer.

659 Background: Cisplatin-based chemotherapy is the recommended therapy for muscle-invasive bladder cancer (MIBC), in the neoadjuvant setting. However, the efficacy of MIBC for chemotherapy is only about 40%. Therefore, predictors of therapy response are urgently needed. Neutrophils form neutrophil extracellular traps (NETs), a network structure, and growing evidence indicated that it could be a prognostic and predictive marker in cancer. Besides, NETs and IgG could reflect the immune response, even may induce immune tolerance. In MIBC, the predictive role of NETs or IgG in chemotherapy resistance is unclear. Methods: This study included 54 patients with MIBC undergoing neoadjuvant chemotherapy. Immunohistochemical staining with NETs was performed on tumor primary lesions before chemotherapy, and the staining intensity was scored. Serum IgG levels in the pre-treatment baseline and 1 month after chemotherapy were also measured for these patients. Results: Citrullinated histone H3 (H3Cit) as a hallmark of NETs, was an independent predictor of chemotherapy resistance as determined by the multivariate logistic regression analyses [OR=5.94, 95% CI 1.20–45.50, P=0.045]. Additionally, in patients with favorable chemotherapy response, serum IgG levels significantly decreased after 1 month of treatment (P=0.0018), while in those with poor response, there was no significant change. Conclusions: The baseline levels of NETs and the change of IgG after 1-month treatment demonstrated predictive capabilities during neoadjuvant chemotherapy, possibly reflecting the immune status. MIBC patients with high NETs and IgG levels were resistant to neoadjuvant chemotherapy, providing new insights into the treatment of MIBC. However, these results require further validation through larger sample studies. Further validation of our findings could provide a theoretical basis regarding NETs inhibitors or IgG antibodies combined with chemotherapy strategy.

Interactive effects of dietary protein and nano-chitosan on growth performance, immune response, and histological aspects of lymphoid organs in broiler chickens

A feeding trial was conducted to assess the effect of partial replacement of dietary soybean meal by three plant protein sources: coconut, rocket seed, and black cumin meals with their combination in the presence or absence of nano-chitosan (NCH) on growth performance and immune response in broiler chickens. Five starter and grower diets were formulated and used from 1 to 42 days of age. The NCH was added to starter and grower diets at 1.0 g/kg. Five-hundred-fifty-day-old Arbor Acres Plus broiler chicks were randomly divided into ten treatments with five equal replications. Final body weight (FBW), body weight gain (BWG), feed intake (FI), feed conversion ratio (FCR), and blood plasma parameters were investigated. Histological aspects of lymphoid organs (thymus: T, bursa of Fabricius: B, and spleen: S) were characterized. Apart from added NCH, the FBW, BWG, and FCR of broilers fed the diets containing the tested plant proteins were significantly superior to the control ones. However, FI of birds fed the diets containing CM alone or combined with RSM plus BCM was significantly reduced. All experimental broilers displayed high plasma levels of IgG compared with the control group. There were significant increases in plasma concentrations of IgM, IgA, and T4 for groups that fed the diets containing RSM, BCM, and mixture of CM, RSM, and BCM compared with their controls. The T3 levels of broilers fed the tested plant proteins were significantly increased compared with the controls. Aside from plant protein source, broilers fed the NCH-enriched diets achieved significant increases in levels of IgM, TAC, and FSH and activities of CAT and SOD but reduced the MDA level compared with control. The interactions between plant protein source and added nano-chitosan were not interrelated. Furthermore, CM, RSM, and BCM can be used as complementary dietary proteins singly or combined with NCH with no adverse effects on growth performance. Addition of NCH molecules has a positive effect on live body weight and increases feed intake compared with control chicks.Graphical

The Anti-SARS-CoV-2 IgG1 and IgG3 Antibody Isotypes with Limited Neutralizing Capacity against Omicron Elicited in a Latin Population a Switch toward IgG4 after Multiple Doses with the mRNA Pfizer-BioNTech Vaccine.

The aim of this study was to analyze the profiles of IgG subclasses in COVID-19 convalescent Puerto Rican subjects and compare these profiles with those of non-infected immunocompetent or immunocompromised subjects that received two or more doses of an mRNA vaccine. The most notable findings from this study are as follows: (1) Convalescent subjects that were not hospitalized developed high and long-lasting antibody responses. (2) Both IgG1 and IgG3 subclasses were more prevalent in the SARS-CoV-2-infected population, whereas IgG1 was more prevalent after vaccination. (3) Individuals that were infected and then later received two doses of an mRNA vaccine exhibited a more robust neutralizing capacity against Omicron than those that were never infected and received two doses of an mRNA vaccine. (4) A class switch toward the "anti-inflammatory" antibody isotype IgG4 was induced a few weeks after the third dose, which peaked abruptly and remained at high levels for a long period. Moreover, the high levels of IgG4 were concurrent with high neutralizing percentages against various VOCs including Omicron. (5) Subjects with IBD also produced IgG4 antibodies after the third dose, although these antibody levels had a limited effect on the neutralizing capacity. Knowing that the mRNA vaccines do not prevent infections, the Omicron subvariants have been shown to be less pathogenic, and IgG4 levels have been associated with immunotolerance and numerous negative effects, the recommendations for the successive administration of booster vaccinations to people should be revised.

Fatigue and sleep quality in Chinese adults with connective tissue disease: A cross-sectional study.

This study aims to evaluate fatigue and sleep quality among adults with connective tissue disease (CTD), and the interrelationship. From April 2020 to February 2021, adult CTD patients hospitalized were invited to complete sociodemographic and disease-related data, Fatigue Severity Scale (FSS), and Pittsburgh Sleep Quality Index (PSQI), as well as laboratorydetection through computer query. Statistical analysis was performed using SPSS 22.0. A total of 363 patients with CTD were included in the study. Of which, 313 patients were accompaniedby single CTD (systemic lupus erythematosus (SLE) = 109, Sjogren's syndrome (SS) = 51, rheumatoidarthritis (RA) = 44, idiopathic inflammatory myopathies (IIM) = 36, Vasculitis = 17, systemic sclerosis (SSc) = 14, other = 42, respectively), and 50 patients had CTD ≥ 2. Compared with CTD = 1, patients with CTD ≥ 2 had longer disease duration, higher erythrocyte sedimentation rate, and higher IgG level (all P < 0.05). The prevalence of poor sleep quality in 363 CTD patients was 61.2%, among which, 59.1% for CTD = 1 and 74.0% for CTD ≥ 2, with significant difference (P = 0.045). Additionally, 75.5% experienced fatigue, and 75.4% for CTD = 1, 76.0% for CTD ≥ 2 (P = 0.927). Fatigue and sleep quality interacted in CTD patients (r = 0.236, P < 0.01; χ2 = 11.302, P = 0.001). Interestingly, no significant differences were found in the prevalence of fatigue and poor sleep quality among CTD subgroups, as well as the FSS score, the seven components of sleep quality and total PSQI score (P > 0.05). More than 3/5 CTD patients experience fatigue and poor sleep quality, and not different among CTD subgroups. Targeted interventions are needed to reduce fatigue, improve sleep quality, and ultimately improve the prognosis of patients with CTD.

Immunogenicity and protective efficacy of a trimeric full-length S protein subunit vaccine for porcine epidemic diarrhea virus

Porcine epidemic diarrhea virus (PEDV) has caused serious economic losses to the pig husbandry worldwide, and the effects of existing commercialized vaccines are suboptimal. Therefore, research to develop an efficacious vaccine for prevention and control of PEDV is essential. In this study, we designed and produced trimerized proteins of full-length PEDV spike (S) protein, S1 subunit, and a tandem of multiple epitopes of S protein using an efficient mammalian expression vector system in HEK 293F cells. The immunogenicity of two commercial adjuvants, M401 and M103, was also evaluated in mice. Enzyme-linked immunosorbent assays demonstrated that all immunized mice generated highly systemic PEDV S-specific IgG and IgA antibodies. Mice in S/M103-immunized group generated the highest neutralizing antibody titer with 1:96. Compared with control group, the subunit vaccines elicited multifunctional CD3+CD4+ and CD3+CD8+ T cells, B220+CD19+ B cells, and CD3-CD49b+ natural killer cells in the spleen. PEDV S/M103 vaccine, which had the best immune effect, was selected for further evaluation in piglets. Immunization with S/M103 vaccine induced high levels of S-specific IgG, IgA, and neutralizing antibodies, and increased the proliferation of peripheral blood mononuclear cells and the expression levels of interferon-γ and interleukin-4 in peripheral blood of piglets. Virus challenge test results showed significantly lower diarrheal index scores and fecal viral loads, and less pathological damage to the intestines in S/M103-immunized piglets than in controls, indicating that S/M103 provides good protection against the virulent virus challenge. Our findings suggest that trimeric PEDV S/M103 has potential as a clinical vaccine candidate.

Molecular, Immunological, and Clinical Characterization of SARS-CoV-2 Infection in Breakthrough-Infected Healthcare Workers During the Last Wave of The Pandemic in Shiraz, Iran

Background: The coronavirus disease 2019 (COVID-19) poses a threat to the global economy and public health. Mutations in the spike protein of the virus can impact the functional characteristics and effectiveness of vaccines. Objectives: This study aimed to analyze mutations in three key regions of the spike protein, investigate clinical presentations, and assess protective immune levels in healthcare workers (HCWs) who had received full vaccine doses but were re-infected. Methods: In this cross-sectional study, 49 breakthrough-infected HCWs were included from November 2021 to May 2022. After confirming COVID-19 reinfection, the SARS-CoV-2 genome was extracted using the ROJE extraction kit, and genetic variation analysis was performed through Sanger sequencing. Blood samples were collected with prior consent, and ELISA tests were performed to determine antibody levels. Clinical presentations were recorded, and independent t-tests revealed no significant gender-based differences in the C-terminal point mutation. Results: In this study, 75.5% (37/49) of the included HCWs were female (P-value &lt; 0.05), and 25 were qualified for PCR and gene sequencing. Mutations were observed in 25, 10, and 1 sequence(s) of the C-terminal domain, N-terminal domain, and RBD regions of the S1 gene, respectively. The mutations had no significant correlation with the patient's gender, age, or occupation, but they were significantly more prevalent in those with underlying diseases. 63.3% (31/49) of patients had high or very high IgG levels, and none had undetectable antibody levels at the time of reinfection. Loss of the sense of smell (69.4% - 34/49), sore throat (65.3% - 32/49), headache (59.2% - 29/49), and cough (57.1% - 28/49) were the most prevalent clinical manifestations (P &gt; 0.05) in breakthrough-infected HCWs, aligning with the pattern of symptoms seen in the Omicron wave. However, the loss of the sense of taste showed significant results concerning clinical manifestation (P &lt; 0.05). The examination of mutations revealed the presence of the Omicron variant in the majority of individuals. Point mutations in the C-terminal region did not significantly vary based on age, gender, or vaccine type. No significant difference was observed between vaccine types and clinical symptoms. Conclusions: In conclusion, this study identified spike protein mutations in reinfections among vaccinated healthcare workers. While mutations were prevalent, no significant correlations were found with demographics or vaccine types. Symptoms resembled the Omicron variant, notably with the loss of the sense of taste as a significant marker. Detectable antibody levels post-reinfection suggest that vaccine-induced immunity remains robust. Continuous monitoring of virus variants is crucial for optimizing vaccination strategies in the face of evolving strains.

Intranasal HD-Ad-FS vaccine induces systemic and airway mucosal immunities against SARS-CoV-2 and systemic immunity against SARS-CoV-2 variants in mice and hamsters.

The outbreak of coronavirus disease 19 (COVID-19) has highlighted the demand for vaccines that are safe and effective in inducing systemic and airway mucosal immunity against the aerosol transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, we developed a novel helper-dependent adenoviral vector-based COVID-19 mucosal vaccine encoding a full-length SARS-CoV-2 spike protein (HD-Ad-FS). Through intranasal immunization (single-dose and prime-boost regimens), we demonstrated that the HD-Ad-FS was immunogenic and elicited potent systemic and airway mucosal protection in BALB/c mice, transgenic ACE2 (hACE2) mice, and hamsters. We detected high titers of neutralizing antibodies (NAbs) in sera and bronchoalveolar lavages (BALs) in the vaccinated animals. High levels of spike-specific secretory IgA (sIgA) and IgG were induced in the airway of the vaccinated animals. The single-dose HD-Ad-FS elicited a strong immune response and protected animals from SARS-CoV-2 infection. In addition, the prime-boost vaccination induced cross-reactive serum NAbs against variants of concern (VOCs; Beta, Delta, and Omicron). After challenge, VOC infectious viral particles were at undetectable or minimal levels in the lower airway. Our findings highlight the potential of airway delivery of HD-Ad-FS as a safe and effective vaccine platform for generating mucosal protection against SARS-CoV-2 and its VOCs.

The Expression of Non B Cell-Derived Immunoglobulins.

Although V(D)J recombination and immunoglobulin (Ig) production are traditionally recognised to occur only in B lymphocytes and plasma cells, the expression of Igs in non-lymphoid cells, which we call nonB cell-derived Igs (nonB Igs), has been documented by growing studies. It has been demonstrated that nonB-Igs can be widely expressed in most cell types, including, but not limited to, epithelial cells, cardiomyocytes, hematopoietic stem/progenitor cells, myeloid cells, and cells from immune-privileged sites, such as neurons and spermatogenic cells. In particular, malignant tumour cells express high level of IgG. Moreover, different from B-Igs that mainly localised on the B cell membrane and in the serum and perform immune defence function mainly, nonB-Igs have been found to distribute more widely and play critical roles in immune defence, maintaining cell proliferation and survival, and promoting progression. The findings of nonB-Igs may provide a wealthier breakthrough point for more therapeutic strategies for a wide range of immune-related diseases.

Expression and Clinical Significance of Non B Cell-Derived Immunoglobulins in the Urinary System and Male Reproductive System.

The urinary system comprises kidneys, ureters, bladder, and urethrawith its primary function being excretion, referring to the physiological process of transporting substances that are harmful or surplus out of the body. The male reproductive system consists of gonads (testis), vas deferens, and accessory glands such as the prostate. According to classical immunology theory, the tissues and organs mentioned above are not thought to produce immunoglobulins (Igs), and any Ig present in the relevant tissues under physiological and pathological conditions is believed to be derived from B cells. For instance, most renal diseases are associated with uncontrolled inflammation caused by pathogenic Ig deposited in the kidney. Generally, these pathological Igs are presumed to be produced by B cells. Recent studies have demonstrated that renal parenchymal cells can produce and secrete Igs, including IgA and IgG. Glomerular mesangial cells can express and secrete IgA, which is associated with cell survival and adhesion. Likewise, human podocytes demonstrate the ability to produce and secrete IgG, which is related to cell survival and adhesion. Furthermore, renal tubular epithelial cells also express IgG, potentially involved in the epithelial-mesenchymal transition (EMT). More significantly, renal cell carcinoma, bladder cancer, and prostate cancer have been revealed to express high levels of IgG, which promotes tumour progression. Given the widespread Ig expression in the urinary and male reproductive systems, continued efforts to elucidate the roles of Igs in renal physiological and pathological processes are necessary.

Role of Pre-Farrow Natural Planned Exposure of Gilts in Shaping the Passive Antibody Response to Rotavirus A in Piglets.

Natural planned exposure (NPE) remains one of the most common methods in swine herds to boost lactogenic immunity against rotaviruses. However, the efficacy of NPE protocols in generating lactogenic immunity has not been investigated before. A longitudinal study was conducted to investigate the dynamics of genotype-specific antibody responses to different doses (3, 2 and 1) of Rotavirus A (RVA) NPE (genotypes G4, G5, P[7] and P[23]) in gilts and the transfer of lactogenic immunity to their piglets. Group 1 gilts received three doses of NPE at 5, 4 and 3 weeks pre-farrow (WPF), group 2 received two doses at 5 and 3 WPF, group 3 received one dose at 5 WPF, and group 4 received no NPE (control group). VP7 (G4 and G5) and truncated VP4* (P[7] and P[23]) antigens of RVA were expressed in mammalian and bacterial expression systems, respectively, and used to optimize indirect ELISAs to determine antibody levels against RVA in gilts and piglets. In day-0 colostrum samples, group 1 had significantly higher IgG titers compared to the control group for all four antigens, and either significantly or numerically higher IgG titers than groups 2 and 3. Group 1 also had significantly higher colostrum IgA levels than the control group for all antigens (except G4), and either significantly or numerically higher IgA levels compared to groups 2 and 3. In piglet serum, group 1 piglets had higher IgG titers for all four antigens at day 0 than the other groups. Importantly, RVA NPE stimulated antibodies in all groups regardless of the treatment doses and prevented G4, G5, P[7] and P[23] RVA fecal shedding prior to weaning in piglets in the absence of viral challenge. The G11 and P[34] RVA genotypes detected from pre-weaning piglets differed at multiple amino acid positions with parent NPE strains. In conclusion, the results of this study suggest that the group 1 NPE regimen (three doses of NPE) resulted in the highest anti-RVA antibody (IgG and IgA) levels in the colostrum/milk, and the highest IgG levels in piglet serum.

Characteristics of innate, humoral and cellular immunity in children with non-severe SARS-CoV-2 infection

The symptoms of children infected with SARS-CoV-2 are mainly asymptomatic, mild, moderate, and a few severe cases. To understand the immune response characteristics of children infected with SARS-COV-2 who do not develop severe cases, 82 children infected with the SARS-CoV-2 delta strain were recruited in this study. Our results showed that high levels of IgG, IgM, and neutralization antibodies appeared in children infected with SARS-CoV-2. SARS-CoV-2 induced upregulation of both pro-inflammatory factors including TNF-α and anti-inflammatory factors including IL-4 and IL-13 in the children, even IL-10. The expression of INF-α in infected children also showed a significant increase compared to healthy children. However, IL-6, one of the important inflammatory factors, did not show an increase in infected children. It is worth noting that a large number of chemokines reduced in the SARS-CoV-2-infected children. Subsequently, TCR Repertoire, TCRβ bias, and preferential usage were analyzed on data of TCR next-generation sequencing from 8 SARS-CoV-2-infected children and 8 healthy controls. We found a significant decrease in TCR clonal diversity and a significant increase in TCR clonal expansion in SARS-CoV-2-infected children compared to healthy children. The most frequent V and J genes in SARS-CoV-2 children were TRBV28 and TRBJ2-1. The most frequently VβJ gene pairing in SARS-CoV-2 infected children was TRBV20-1-TRBJ2-1. The strong antiviral antibody levels, low expression of key pro-inflammatory factors, significant elevation of anti-inflammatory factors, and downregulation of many chemokines jointly determine that SARS-CoV-2-infected children rarely develop severe cases. Overall, our findings shed a light on the immune response of non-severe children infected with SARS-CoV-2.

Evaluation of a new fusion antigen, cd loop and HAP2-GCS1 domain (cd-HAP) of Plasmodium falciparum Generative Cell Specific 1 antigen formulated with various adjuvants, as a transmission blocking vaccine

BackgroundMalaria is a major global health challenge, and for the elimination and eradication of this disease, transmission-blocking vaccines (TBVs) are a priority. Plasmodium falciparum Generative Cell Specific 1 (PfGCS1), a promising TBV candidate, is essential for gamete fertilization. The HAP2-GCS1 domain of this antigen as well as its cd loop could induce antibodies that partially inhibit transmission of P. falciparum.MethodsIn the current study, a new synthetic fusion antigen containing cd loop and HAP2-GCS1 domain (cd-HAP) of PfGCS1 was evaluated as a transmission blocking vaccine candidate. Initially, the profile of naturally acquired IgG antibodies to the cd-HAP antigen was analysed in Iranian individuals infected with P. falciparum, to confirm that this new fusion protein has the appropriate structure containing common epitopes with the native form of PfGCS1. Then, the immunogenicity of cd-HAP was evaluated in BALB/c mice, using different adjuvant systems such as CpG, MPL, QS-21, and a combination of them (CMQ). Furthermore, the blocking efficacy of polyclonal antibodies induced against these formulations was also assessed by oocyst intensity and infection prevalence in the Standard Membrane Feeding Assay (SMFA).ResultsThe naturally acquired antibodies (dominantly IgG1 and IgG3 subclasses) induced in P. falciparum-infected individuals could recognize the cd-HAP antigen which implies that the new fusion protein has a proper conformation that mimics the native structure of PfGCS1. Concerning the immunogenicity of cd-HAP antigen, the highest IgG levels and titers, by a Th1-type immune profile, and elevated antibody avidity were induced in mice immunized with the cd-HAP antigen formulated with a combination of adjuvants (P < 0.0001). Additionally, cytokine profiling of the immunized mice displayed that a high level of IFN-γ response, a Th1-type immune response, was produced by splenocytes from immunized mice that received cd-HAP antigen in combination with CMQ adjuvants (P < 0.0001). This formulation of cd-HAP antigen with CMQ adjuvants could reduce oocyst intensity and infection prevalence by 82%, evidenced by the SMFA and hold significant implications for future malaria vaccine development.ConclusionAltogether, the results showed that cd-HAP antigen formulated with a combination of the adjuvants (CMQ), could be a promising formulation to develop a PfGCS1-based transmission-blocking vaccine.

Evaluation of immunogenicity-induced DNA vaccines against different SARS-CoV-2 variants

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 and caused the coronavirus disease 2019 (COVID-19) pandemic worldwide. As of September 2023, the number of confirmed coronavirus cases has reached over 770 million and caused nearly 7 million deaths. The World Health Organization assigned and informed the characterization of variants of concern (VOCs) to help control the COVID-19 pandemic through global monitoring of circulating viruses. Although many vaccines have been proposed, developing an effective vaccine against variants is still essential to reach the endemic stage of COVID-19. We designed five DNA vaccine candidates composed of the first isolated genotype and major SARS-CoV-2 strains from isolated Korean patients classified as VOCs, such as Alpha, Beta, Gamma, and Delta. To evaluate the immunogenicity of each genotype via homologous and heterologous vaccination, mice were immunized twice within a 3-week interval, and the blood and spleen were collected 1 week after the final vaccination to analyze the immune responses. The group vaccinated with DNA vaccine candidates based on the S genotype and the Alpha and Beta variants elicited both humoral and cellular immune responses, with higher total IgG levels and neutralizing antibody responses than the other groups. In particular, the vaccine candidate based on the Alpha variant induced a highly diverse cytokine response. Additionally, we found that the group subjected to homologous vaccination with the S genotype and heterologous vaccination with S/Alpha induced high total IgG levels and a neutralization antibody response. Homologous vaccination with the S genotype and heterologous vaccination with S/Alpha and S/Beta significantly induced IFN-γ immune responses. The immunogenicity after homologous vaccination with S and Alpha and heterologous vaccination with the S/Alpha candidate was better than that of the other groups, indicating the potential for developing novel DNA vaccines against different SARS-CoV-2 variants.

Serological Survey of Severe Acute Respiratory Syndrome Coronavirus -2 (Sars-Cov-2) among Frontline Health Workers in Northwest Nigeria

Background: Serological testing of SARS-CoV-2-specific IgG/IgM antibodies is an important complement to Real Time-PCR (RT-PCR) for surveillance and outbreak investigations. The study therefore aimed to assess the serological survey of SARS-COV-2 among frontline health workers using specific IgG/IgM antibodies.&#x0D; Methods: The study was a cross-sectional design. A self-administered questionnaire was used to obtain biodata. Rapid diagnostic test kits were used for the study in which samples reacted with COVID-19 antigen-coated particles in the test cassette and the complex formed produced readable bands indicating the presence of SARS-COV19 in the tested subject. Data obtained were analyzed using Stata v15.&#x0D; Results: The prevalence of SARS-CoV-2 among the study sample was 39.0% and 14.9% for IgG and IgM respectively. Prevalence was highest in the outpatient department (IgG; 70.0%, IgM; 17.1%). IgG positivity was observed more among doctors while positivity for IgG was seen in 78.6% of persons with previous diagnoses. IgM was significantly associated with contact with patients having shortness of breath, p-value &lt; 0.05.&#x0D; Conclusion: This study demonstrated a high level of SARS-COV19 IgG indicating past infection and IgM suggesting recent exposure or ongoing infection among this group of workers compared to others within the hospital settings. The role of serological testing cannot be over-emphasized in the periodic screening and prompt treatment of health workers before they manifest symptoms or become capable of spreading the disease to innocent patients and or co-health workers.

The effect of long-term traditional Chinese medicine treatment on extra-articular lesions of rheumatoid arthritis patients based on propensity score matching: A retrospective cohort study

ObjectiveTo explore the efficacy of long-term traditional Chinese medicine (TCM) treatment on the occurrence of extra-articular lesions in rheumatoid arthritis (RA) patients. MethodsOur retrospective cohort study included patients diagnosed with RA between January 2018 to December 2019. Patients were divided into TCM treatment group and control group according to whether they received TCM treatment for more than three months. Propensity score matching (PSM) was used to balance covariates between groups. The occurrence time of extra-articular lesions, including interstitial lung disease, Sjögren's syndrome, and anemia, was calculated for both groups after PSM. Additionally, clinical indicators that may affect the occurrence of extra-articular lesions in RA were included in Cox multivariate regression analysis to explore prognostic factors related to RA. ResultsA total of 883 RA patients were initially included in our study, with 481 in the TCM treatment group and 279 in the control group. TCM treatment improved all clinical indicators of RA patients, and there was a higher degree of support, confidence, and lift between TCM treatment and the improvement of clinical indicators. There was no significant difference in the rate of extra-articular lesions occurrence between the two groups. After PSM, the median occurrence time of interstitial lung disease, Sjögren's syndrome and anemia in the TCM treatment group were 30.767, 21.370 and 31.970 months, respectively. While in the control group, it was 15.911, 14.667 and 11.825 months, respectively. Cox multivariate regression analysis indicated that TCM treatment was a protective factor for the occurrence of extra-articular lesions in RA, while abnormally high level of IgG was an independent factor for interstitial lung disease and C4 was an independent factor for Sjögren's syndrome. Moreover, a longer duration of TCM usage was associated with a later occurrence of extra-articular lesions. ConclusionLong-term TCM treatment not only positively affects the occurrence time of extra-articular lesions in RA patients, but also helps reduce the risk of extra-articular lesions occurrence. TCM can be applied flexibly throughout the treatment process for RA patients.