Serum Antibody Levels Research Articles

Efficacy evaluation of B cell targeting drugs and the involved mechanism of action study in humanized BAFF transgenic SLE mice model

Abstract The B cell activating factor (BAFF) functions as a crucial factor in B cell survival, and heightened BAFF expression can augment the presence of autoreactive B cells, thereby fostering autoimmunity like Systemic Lupus Erythematosus (SLE). This study introduces transgenic mouse strains with human BAFF overexpression, offering insights into SLE mechanisms and B cell-targeting therapies. Human BAFF overexpression in B6-hBAFF mice led to a substantial rise in Igs and anti-dsDNA levels from 6 weeks of age, persistently escalating with time compared to wild-type mice. A heightened population of B cells but a reduced ratio of T cells was observed. At week 25 of age, B6-hBAFF mice developed lupus nephritis. Belimumab, a BAFF antibody administrated to BAFF transgenic mice demonstrated the effectively reduced serum antibody levels after 16 weeks of dosing. Belimumab ameliorated kidney function by decreasing urine albumin-to-creatinine ratio and IgA deposition after 20 weeks of treatment. Mice were also treated with Enpatoran (TLR7/8 inhibitors) and BTK inhibitor Orelabrutinib. Only the BTK inhibitor Orelabrutinib significantly eliminated serum Igs levels. Enpatoran exhibited a similar ability to Orelabrutinib in reducing T follicular helper cell and plasma cell populations spleen and lymph nodes. In summary, the humanized BAFF transgenic SLE model proves to be a valuable tool for preclinical efficacy studies in SLE treatment and understanding pathogenesis.

Recombinant Human Proteoglycan Aggrecan-G1 Domain-induced Arthritis (GIA) Mouse Model.

The recombinant human proteoglycan aggrecan-G1 domain (rhG1)-induced arthritis (GIA) mouse model is a complex model of rheumatoid arthritis (RA). In GIA, autoimmune arthritis is induced by repeated intraperitoneal immunization of genetically susceptible BALB/c mice with the rhG1 antigen emulsified in the adjuvant dimethyldioctadecylammonium (DDA). This article describes the steps for producing and purifying the rhG1 antigen, the immunization protocol, methods for following the clinical picture of arthritis, and the evaluation of relevant laboratory parameters. In this model, the autoimmune arthritis develops stepwise, similar to RA: First is the preclinical stage (after the first immunization, days 0-20) with no sign of inflammation but detectable T and B cell activation; next, the stage of early arthritis (after the second immunization, days 21-41), where the first definitive signs of arthritis appear together with autoantibody production; and then the severe late-stage arthritis (after the third immunization, after day 42), which presents with massive inflammation of the limbs, leading to cartilage and bone destruction and finally ankylosis. The protocols described here provide sufficient information for investigators to use the GIA model to study different aspects of autoimmune arthritis. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol: Induction of recombinant human proteoglycan aggrecan-G1 domain (rhG1)-induced arthritis (GIA) Support Protocol 1: Production of rhG1-Xa-mFc2a fusion protein with CHOK1 mammalian expression system Support Protocol 2: Purification of the rhG1-Xa-mFc2a fusion protein by affinity chromatography Support Protocol 3: Preparation of DDA adjuvant Support Protocol 4: Clinical assessment of arthritis Support Protocol 5: Measurement of serum antibody levels and cytokines Support Protocol 6: Measurement of rhG1-induced proliferation and cytokine production in spleen cell culture Support Protocol 7: Histological assessment of arthritic limbs Support Protocol 8: Evaluation of arthritis with micro-computed tomography.

JMJD6 Autoantibodies as a Potential Biomarker for Inflammation-Related Diseases.

Inflammation is closely associated with cerebrovascular diseases, cardiovascular diseases, diabetes, and cancers, and it is accompanied by the development of autoantibodies in the early stage of inflammation-related diseases. Hence, it is meaningful to discover novel antibody biomarkers targeting inflammation-related diseases. In this study, Jumonji C-domain-containing 6 (JMJD6) was identified by the serological identification of antigens through recombinant cDNA expression cloning. In particular, JMJD6 is an antigen recognized in serum IgG from patients with unstable angina pectoris (a cardiovascular disease). Then, the serum antibody levels were examined using an amplified luminescent proximity homogeneous assay-linked immunosorbent assay and a purified recombinant JMJD6 protein as an antigen. We observed elevated levels of serum anti-JMJD6 antibodies (s-JMJD6-Abs) in patients with inflammation-related diseases such as ischemic stroke, acute myocardial infarction (AMI), diabetes mellitus (DM), and cancers (including esophageal cancer, EC; gastric cancer; lung cancer; and mammary cancer), compared with the levels in healthy donors. The s-JMJD6-Ab levels were closely associated with some inflammation indicators, such as C-reactive protein and intima-media thickness (an atherosclerosis index). A better postoperative survival status of patients with EC was observed in the JMJD6-Ab-positive group than in the negative group. An immunohistochemical analysis showed that JMJD6 was highly expressed in the inflamed mucosa of esophageal tissues, esophageal carcinoma tissues, and atherosclerotic plaques. Hence, JMJD6 autoantibodies may reflect inflammation, thereby serving as a potential biomarker for diagnosing specific inflammation-related diseases, including stroke, AMI, DM, and cancers, and for prediction of the prognosis in patients with EC.

Establishment of a mouse allergy model for Culicoides (Diptera: Ceratopogonidae).

Culicoides is a genus of ubiquitous biting midges (Ceratopogonidae). Female midges have blood-sucking habit. They not only bite and harass humans and animals but also may be an important vector of disease transmission. Therefore, building an animal allergy model caused by Culicoides biting is very beneficial for studying its pathogenesis and exploring the therapeutic methods. Kunming mice were used in this study to build the model and sensitised by two-step injection of midge extracts. Scratching behaviour and histological examination were used to check the immediate and delayed responses. Immunoglobulin E (IgE) and Immunoglobulin G (IgG) were detected using indirect enzyme-linked immunosorbent assay (ELISA) assay. Splenic cell proliferation and cytokine production were determined using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) and ELISA assays. The response of cytokine gene expression to midge stimulation was analysed through quantitative real-time polymerase chain reaction (qPCR). Behavioural results revealed a significant increase in scratching frequency among the midge-sensitised animals (p < 0.05). Histological examination showed more inflammatory cytokine infiltration at the injection site of midge-sensitised mice comparing to the ones in the control group. The serum levels of IgE and IgG1 antibodies in the midge-sensitised group were significantly elevated (p < 0.05). After splenocytes were stimulated in vitro with midge extracts, the midge-sensitised group's splenocyte count significantly increased in comparison to the control group. The midge-sensitised group's qPCR data revealed a down-regulation of tumor necrosis factor alpha (TNF-α) expression and an increase in the expression of interleukin (IL)-4, IL-5, IL-10 and IL-13 but not in the control group (p < 0.05). In this study, an animal model of Culicoides-mouse sensitisation was successfully constructed using a two-step method. The mode of administration of the model was in good agreement with the natural immune pathway, and the immune response induced by the sensitisation of the model was similar to that produced by the bite of a midge.

Higher correlation between neutralizing antibodies and surrogate neutralizing or binding antibodies in COVID-19 patients than vaccine recipients.

This study determined the seropositive rates and levels of antibodies to severe acute respiratory syndrome coronavirus-2 in 50 patients and 108 vaccinees using microneutralization test (MNT), surrogate virus neutralization test (sVNT), chemiluminescent microparticle immunoassay (CMIA), and electrochemiluminescence immunoassay (ECLIA). MNT, as the reference method, employed living clade S and Delta viruses to measure neutralizing (NT) antibodies, while sVNT employed wild type strain and Delta receptor-binding domains (RBD) as the test antigens to measure sVNT antibodies. CMIA and ECLIA employed only one version of RBD to measure the binding antibodies. Our study performed S gene sequencing of the test virus to exclude undesired mutants that might lead to changes in antibody levels in MNT assay. We showed that spike protein amino acid sequences of our Delta virus contained 13 amino acid changes, with 3 related to the reduced neutralization. The MNT assay showed a significant reduction in seropositive rates and antibody levels in the patients' sera when the Delta variant replaced clade S as the test virus. In contrast, the seropositive rates determined by sVNT assay using wild type strain RBD and Delta RBD were non-significantly different, suggesting that sVNT assay could not identify the difference between the antigenicity of wild type RBD and Delta RBD. Furthermore, the correlation between the levels of NT and sVNT antibodies was moderate with the patients' sera but modest with the post-vaccination sera. The seropositive rates in the patients, as determined by CMIA or ECLIA, were not different from the MNT assay using clade S, but not Delta, as the test virus. In all analyses, the correlations between the antibody levels measured by MNT and the other 3 assays were modest to moderate, with the r-values of 0.3500-0.7882.

Evaluation of Immune Protection of a Bivalent Inactivated Vaccine against Aeromonas salmonicida and Vibrio vulnificus in Turbot

The Aeromonas salmonicida is responsible for causing furunculosis in various fish species. Furunculosis is a ubiquitous disease that affects the aquaculture industry and causes the mass mortality of turbot. Vibrio vulnificus is a pathogen that causes skin ulcers and hemorrhagic septicemia in fish, resulting in significant mortality in aquaculture. In this study, we have established a bivalent inactivated vaccine against A. salmonicida and V. vulnificus with Montanide™ ISA 763 AVG as an adjuvant. This bivalent inactivated vaccine was used to immunize turbot by intraperitoneal injection, and the relevant immune indexes were detected. The results demonstrate that the bivalent inactivated vaccine exhibited a relative percent survival (RPS) of 77% following A. salmonicida and V. vulnificus intraperitoneal challenge. The vaccinated group exhibited higher levels of acid phosphatase activity and lysozyme activity compared to the control group. ELISA results showed a significant increase in serum antibody levels in immunized turbot, which was positively correlated with immunity. In the kidney tissue, related immune genes (TLR5, CD4, MHCI and MHCII) were up-regulated significantly, showing that the vaccine can induce cellular and humoral immune responses in turbot. In conclusion, the bivalent inactivated vaccine against A. salmonicida and V. vulnificus was immunogenic, efficiently preventing turbot from infection, which has the potential to be applied in aquaculture.

Macrophage membrane-coated Eucommia ulmoides polysaccharides-loaded PLGA nanoparticles as an effective antigen-targeted delivery system

Polysaccharides derived from Eucommia ulmoides leaves have immune-regulating, hypoglycemic, anti-tumor, and other beneficial functions. As a drug delivery system, polylactic-glycolic acid copolymer (PLGA) offers advantages like immunogenicity enhancement, improved drug absorption, and increased drug bioavailability. Currently, macrophage membranes are successfully employed in biomimetic nanomaterials to enhance drug utilization and extend drug administration time in the body, exhibiting good immunogenicity and organ targeting. In this study, we developed biomimetic PsEUL PLGA nanoparticles (NPs) coated with macrophage membrane (MM-PPsEUL) and examined their immune activity in vitro and in vivo. In vitro, MM-PPsEUL increased the phagocytic efficiency of macrophages without affecting their activity. In vivo, MM-PPsEUL significantly elevated the immune organ index of mice and upregulated the level of ovalbumin-specific IgG antibodies in serum. Simultaneously, it increased the expressions of cytokines IFN-γ and IL-4, as well as the levels of TLR4, MyD88, TRAF6, and NF-κB p65 proteins in mice spleen. MM-PPsEUL also exhibited a targeting effect on inguinal lymph nodes and slowed down the release rate of antigens, thereby inducing a prolonged immune response. In summary, MM-PPsEUL provides sustained release capabilities and can induce both humoral and cellular immune responses. This makes MM-PPsEUL NPs a promising antigen-targeted delivery system.

Investigation of an Mpox Outbreak Affecting Many Vaccinated Persons in Chicago, Illinois-March 2023-June 2023.

After months of few mpox cases, an increase in cases was reported in Chicago during May 2023, predominantly among fully vaccinated (FV) patients. We investigated the outbreak scope, differences between vaccinated and unvaccinated patients, and hypotheses for monkeypox virus (MPXV) infection after vaccination. We interviewed patients and reviewed medical records to assess demographic, behavioral, and clinical characteristics; mpox vaccine status; and vaccine administration routes. We evaluated serum antibody levels after infection and compared patient viral genomes with MPXV sequences in available databases. We discussed potential vaccine compromise with partners who manufactured, handled, and administered the vaccine associated with breakthrough infections. During 18 March-27 June 2023, we identified 49 mpox cases; 57% of these mpox patients were FV. FV patients received both JYNNEOS doses subcutaneously (57%), intradermally (7%), or via heterologous administration (36%). FV patients had more median sex partners (3; interquartile range [IQR] = 1-4) versus not fully vaccinated patients (1; IQR = 1-2). Thirty-six of 37 sequenced specimens belonged to lineage B.1.20 of clade IIb MPXV, which did not demonstrate any amino acid changes relative to B.1, the predominant lineage from May 2022. Vaccinated patients demonstrated expected humoral antibody responses; none were hospitalized. No vaccine storage excursions were identified. Approximately 63% of people at risk for mpox in Chicago were FV during this period. Our investigation indicated that cases were likely due to frequent behaviors associated with mpox transmission, even with relatively high vaccine effectiveness and vaccine coverage. Cases after vaccination might occur in similar populations.

Francisella tularensis-specific antibody levels in sera from Swedish patients with suspected tularemia during a 13-year period.

For a majority of tularemia patients, serology is the basis for the diagnosis. The aim of this study was to perform an analysis of the samples analyzed at a Swedish reference laboratory for the presence of Francisella tularensis-specific antibody levels in sera from individuals with suspected tularemia. Annual and monthly variations of the total number of samples and proportions of positive samples were analyzed, as well as the influence of age and gender. We performed a retrospective analysis of the presence of F. tularensis-specific antibodies in serological samples from patients with suspected tularemia analyzed during the period 2010 - 2022 at the University Hospital of Umeå in Sweden, a national reference laboratory, by use of various statistical methods. In total, some 15,100 serum samples had been analyzed for the presence of IgG and IgM antibodies by ELISA during the 13-year period. Overall, there were higher number of samples with IgG positive or borderline titers, 2,522 and 921, respectively, than with IgM positive or borderline titers, 1,802 and 409, respectively. Repeated samples were obtained from some 1,930 individuals and approximately a third of the cases, which were initially seronegative, had seroconverted when resampled. Peak number of monthly samples were recorded in August and September, > 3,000. Annual numbers varied greatly and peak numbers were observed in 2015 and 2019, 1,832 and 2,250, respectively, whereas some other years the numbers were 700 - 800. There was also much variation in the annual and monthly percentages of positive samples and they varied between less than 10% to greater than 20%. The highest percentages of positive samples were recorded in September and October. IgG and IgM titers declined with age and these differences were highly significant for IgG titers, with decreasing average titers for each 20-year interval. Collectively, the data demonstrate the marked annual and seasonal variations in tularemia sampling occurring in Sweden. Also, the proportion of positive samples increased during months and years with peak number of samples. Another notable finding was that average antibody titers decreased with increased age.

Experimental trials of predicted CD4+ and CD8+ T-cell epitopes of respiratory syncytial virus.

Respiratory syncytial virus (RSV) is the most common cause of viral lower respiratory tract infections (LRTIs) in young children around the world and an important cause of LRTI in the elderly. The available treatments and FDA-approved vaccines for RSV only lessen the severity of the infection and are recommended for infants and elderly people. We focused on developing a broad-spectrum vaccine that activates the immune system to directly combat RSV. The objective of this study is to identify CD4+ and CD8+ T-cell epitopes using an immunoinformatics approach to develop RSV vaccines. The efficacy of these peptides was validated through in-vitro and in-vivo studies involving healthy and diseased animal models. For each major histocompatibility complex (MHC) class-I and II, we found three epitopes of RSV proteins including F, G, and SH with an antigenic score of >0.5 and a projected SVM score of <5. Experimental validation of these peptides on female BALB/c mice was conducted before and after infection with the RSV A2 line 19f. We found that the 3RVMHCI (CD8+) epitope of the F protein showed significant results of white blood cells (19.72 × 103 cells/μl), neutrophils (6.01 × 103 cells/μl), lymphocytes (12.98 × 103 cells/μl), IgG antibodies (36.9 µg/ml), IFN-γ (86.96 ng/L), and granzyme B (691.35 pg/ml) compared to control at the second booster dose of 10 µg. Similarly, 4RVMHCII (CD4+) of the F protein substantially induced white blood cells (27.08 × 103 cells/μl), neutrophils (6.58 × 103 cells/μl), lymphocytes (16.64 × 103 cells/μl), IgG antibodies (46.13 µg/ml), IFN-γ (96.45 ng/L), and granzyme B (675.09 pg/ml). In-vitro studies showed that 4RVMHCII produced a significant level of antibodies in sera on day 45 comparable to mice infected with the virus. 4RVMHCII also induced high IFN-γ and IL-2 secretions on the fourth day of the challenge compared to the preinfectional stage. In conclusion, epitopes of the F protein showed considerable immune response and are suitable for further validation.

Expression and clinical significance of pattern recognition receptor-associated genes in hand, foot and mouth disease

Objective: To explore which pattern recognition receptors (PRRs) play a key role in the development of hand, foot, and mouth disease (HFMD) by analyzing PRR-associated genes. Methods: We conducted a comparative analysis of PRR-associated gene expression in human peripheral blood mononuclear cells (PBMCs) infected with enterovirus 71 (EV-A71) which were derived from patients with HFMD of different severities and at different stages. A total of 30 PRR-associated genes were identified as significantly upregulated both over time and across different EV-A71 isolates. Subsequently, ELISA was employed to quantify the expression of the six most prominent genes among these 30 identified genes, specifically, BST2, IRF7, 1FI16, TRIM21, MX1, and DDX58. Results: Compared with those at the recovery stage, the expression levels of BST2 (P=0.027), IFI16 (P=0.016), MX1 (P=0.046) and DDX58 (P=0.008) in the acute stage of infection were significantly upregulated, while no significant difference in the expression levels of IRF7 (P=0.495) and TRIM21 (P=0.071) was found between different stages of the disease. The expression levels of BST2, IRF7, IFI16 and MX1 were significantly higher in children infected with single pathogen than those infected with mixed pathogens, and BST2, IRF7, IFI16 and MX1 expression levels were significantly lower in coxsackie B virus (COXB) positive patients than the negative patients. Expression levels of one or more of BST2, IRF7, IFI16, TRIM21, MX1 and DDX58 genes were correlated with PCT levels, various white blood cell counts, and serum antibody levels that reflect disease course of HFMD. Aspartate aminotransferase was correlated with BST2, MX1 and DDX58 expression levels. Conclusions: PRR-associated genes likely initiate the immune response in patients at the acute stage of HFMD.

Analysis of the level of protective serum antibody after third dose of different COVID-19 vaccines

A new coronavirus (SARS-CoV-2), causing COVID-19 (coronavirus disease 2019), is a member of the Coronaviridae family. The benefits of the primary COVID-19 vaccination far outweigh the risks. Nevertheless, the risks associated with too early and too frequent boosters should be considered, especially when vaccines have immune-mediated effects like myocarditis, which is more commonly associated with the second dose of some mRNA vaccines. Booster vaccinations against SARS-CoV-2 are needed because of either reduced immunity to the original vaccine or evolved viruses producing immunity to the initial vaccine antigens. So, the aim of this study was to detect the difference in neutralizing anti-RBD antibodies between the third and second doses of COVID-19 vaccines. A study was performed among 29 eligible participants in Birjand (Iran). Blood samples were taken from all participants 2–4 weeks after the third dose. In the next step, humoral responses were assessed with a kit detecting neutralization of SARS-CoV-2. SPSS software version 22.0 (SPSS Inc., Chicago, IL) was used to analyze the data. The mean age of cases was 35.62±8.72 years, with a range of 21–53 years. The obtained results showed that all vaccines significantly had a higher efficacy in the third dose than the second. Participants who received Vaxzevria in the second dose and PastoCovac Plus in the third dose had more immunogenicity. According to the results of this study, a third dose of the vaccine should be given to persons aged ≥20 years to provide an increased level of protection against COVID-19. Especially, participants who received Sputnik-V and Vaxzevria in the second dose and PastoCovac Plus in the third dose showed a more effective immune response against the virus.

Analysis of the level of protective serum antibody after third dose of different COVID-19 vaccines

A new coronavirus (SARS-CoV-2), causing COVID-19 (coronavirus disease 2019), is a member of the Coronaviridae family. The benefits of the primary COVID-19 vaccination far outweigh the risks. Nevertheless, the risks associated with too early and too frequent boosters should be considered, especially when vaccines have immune-mediated effects like myocarditis, which is more commonly associated with the second dose of some mRNA vaccines. Booster vaccinations against SARS-CoV-2 are needed because of either reduced immunity to the original vaccine or evolved viruses producing immunity to the initial vaccine antigens. So, the aim of this study was to detect the difference in neutralizing anti-RBD antibodies between the third and second doses of COVID-19 vaccines. A study was performed among 29 eligible participants in Birjand (Iran). Blood samples were taken from all participants 2–4 weeks after the third dose. In the next step, humoral responses were assessed with a kit detecting neutralization of SARS-CoV-2. SPSS software version 22.0 (SPSS Inc., Chicago, IL) was used to analyze the data. The mean age of cases was 35.62±8.72 years, with a range of 21–53 years. The obtained results showed that all vaccines significantly had a higher efficacy in the third dose than the second. Participants who received Vaxzevria in the second dose and PastoCovac Plus in the third dose had more immunogenicity. According to the results of this study, a third dose of the vaccine should be given to persons aged ≥20 years to provide an increased level of protection against COVID-19. Especially, participants who received Sputnik-V and Vaxzevria in the second dose and PastoCovac Plus in the third dose showed a more effective immune response against the virus.

HERPES SIMPLEX VIRUS-1 SUSCEPTIBILITY AS A RISK FACTOR FOR SEPSIS, WITH CYTOMEGALOVIRUS SUSCEPTIBILITY ELEVATING SEVERITY: INSIGHTS FROM A BIDIRECTIONAL MENDELIAN RANDOMIZATION STUDY.

Objective: We conducted a two-sample bidirectional Mendelian randomization (MR) study to investigate the causal relationships between herpes viruses and sepsis. Methods: Publicly available genome-wide association study data were used. Four viruses, HSV-1, HSV-2, EBV, and CMV, were selected, with serum positivity and levels of antibody in serum as the herpes virus data. Results: In forward MR, susceptibility to HSV-1 was a risk factor for sepsis. The susceptibility to CMV showed a severity-dependent effect on sepsis and was a risk factor for the 28-day mortality from sepsis, and was also a risk factor for 28-day sepsis mortality in critical care admission. The EBV EA-D antibody level after EBV infection was a protective factor for 28-day sepsis mortality in critical care admission, and CMV pp28 antibody level was a risk factor for 28-day sepsis mortality in critical care admission. No statistically significant causal relationships between HSV-2 and sepsis were found. No exposures having statistically significant association with sepsis critical care admission as an outcome were found. In reverse MR, the sepsis critical care admission group manifested a decrease in CMV pp52 antibody levels. No causal relationships with statistical significance between sepsis exposure and other herpes virus outcomes were found. Conclusion: Our study identifies HSV-1 susceptibility as a sepsis risk, with CMV susceptibility elevating severity. Varied effects of EBV and CMV antibodies on sepsis severity are noted. Severe sepsis results in a decline in CMV antibody levels. Our results help prognostic and predictive enrichment and offer valuable information for precision sepsis treatment.

Field testing of recombinant subunit vaccines against Teladorsagia circumcincta in lambing ewes demonstrates a lack of efficacy in the face of a multi-species parasite challenge

IntroductionWe previously demonstrated efficacy of an 8-antigen recombinant subunit vaccine against a single species homologous Teladorsagia circumcincta challenge in lambs and in lambing ewes in pen trials. We subsequently demonstrated efficacy of a simplified, 2-antigen, version of this vaccine in lambs in pen trials. Here, we test both vaccines in lambing ewes in a field setting.MethodsIn the work presented here, 12 adjacent plots were seeded with a mixed infection of several common species of parasitic nematodes of sheep in temperate regions, including T. circumcincta. Ewes (n = 144), in groups of 12, grazed for 2 years on these plots and, in the first year, six of these groups of ewes were vaccinated with a 2-antigen prototype vaccine against T. circumcincta prior to mating and then again prior to lambing. In the following year these ewes were immunised again, this time with the 8-antigen prototype vaccine against T. circumcincta prior to mating and then prior to lambing. Throughout both seasons antigen-specific serum antibody levels in ewes and faecal worm egg counts (FEC) in ewes and their lambs were monitored, along with nematode species diversity at lambing.ResultsImmunised ewes produced elevated serum antibody levels to each of the vaccine antigens following immunisation but their FEC levels were not statistically significantly impacted by vaccination with either vaccine. FEC levels were also not impacted in lambs co-grazing the pastures with these immunised ewes. Nematode species diversity was not significantly impacted by vaccination in either year.DiscussionThe immunosuppressive effects of co-infecting gastrointestinal nematodes, the absence of vaccine cross-protection against co-infecting species and the influence of the periparturient relaxation in immunity probably all contributed to the inability of either vaccine to protect against T. circumcincta infection in field trials in the work presented here.

Comparison of the efficacy of Aeromonas veronii ΔhisJ vaccine in Carassius auratus via different immunization routes.

Aeromonas veronii is a significant pathogen to various aquatic life. Infections in fish can lead to high mortality rates, causing substantial economic losses in aquaculture. Vaccination is proposed as a substitute for antibiotics in aquaculture to decrease disease-related mortality and morbidity. Our study previously constructed a hisJ-deleted strain of A. veronii, which provided protective effect to Loach. To further assess the vaccine's applicability, this study evaluated its genetic stability and safety, and the immune protective effects in Carassius auratus through four distinct administration routes: intraperitoneal injection, intramuscular injection, oral administration, and immersion, to determine the efficacy of these administration routes. The results showed that the vaccine remained genetically stable after 45 generations. Immunization via these administration routes was safe for Carassius auratus, with intraperitoneal and intramuscular injections causing stronger adverse reactions. Immersion immunization resulted in mild adverse reactions, and no significant adverse reactions were observed following oral immunization. Immunizing Carassius auratus at safe concentrations via these routes enhanced the phagocytic activity in serum, increased the levels of non-specific immune-related enzymes (ACP, AKP, C3, C4, LZM, SOD, and IgM), and improved specific serum antibody levels. It also elevated levels of cytokines related to inflammatory responses (IL-1β, IL-10, TNF-α, TGF-β) in organ tissues (liver, spleen, kidney, mid-post intestine, and gills). The survival rates of Carassius auratus were measured after challenging with the virulent strain A. veronii TH0426, resulting in the relative survival rates of 64% for Intraperitoneal vaccine group, 56% for Intramuscular vaccine group, 52% for oral vaccine group, and 48% for immersion vaccine group. Analysis of bacterial load in the liver, spleen, and kidney post-challenge showed a decreasing trend in the control group, indicating that the vaccine strain ΔhisJ could gradually restrict the rapid proliferation of bacteria in these tissues, thereby providing a certain level of immune protection against A. veronii. In brief, the vaccine strain ΔhisJ can serve as a safe live attenuated vaccine for Carassius auratus, and this study lays the foundation for the development of live attenuated vaccines against Aeromonas veronii.

Comparative Immunogenicity and Neutralization Potency of Four Approved COVID-19 Vaccines in BALB/c Mice.

Since the outbreak of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), several vaccine candidates have been developed within a short period of time. Although the potency of these vaccines was evaluated individually, their comparative potency was not comprehensively evaluated. To compare the immunogenicity and neutralization efficacy of four approved COVID-19 vaccines in Iran, including: PastoCovac Plus, Sinopharm, SpikoGen, and Noora in BALB/c mice. Different groups of female BALB/c mice were vaccinated with three doses of each vaccine. The serum levels of antibodies against the viral receptor binding domain (anti-RBD) and spike (anti-spike) protein as well as the vaccine formulation (anti-vaccine) were evaluated using enzyme-linked immunosorbent assay (ELISA). The neutralization efficacy of these four vaccines was assessed through four neutralization assays: conventional virus neutralization test (cVNT), pseudotype virus neutralization test (pVNT), surrogate virus neutralization test (sVNT), and inhibition flow cytometry. All four vaccines induced seroconversion in vaccinated animals. All vaccines successfully induced high levels of anti-vaccine antibody; however, PastoCovac Plus and Sinopharm vaccines induced significantly higher levels of anti-RBD antibody titer compared to Noora and SpikoGen. Moreover, the results of the antibody response were corroborated by the virus neutralization tests, which revealed very weak neutralization potency by Noora and SpikoGen in all tests. Our results indicate significant immunogenicity and neutralization efficacy induced by PastoCovac Plus and Sinopharm, but not by Noora and SpikoGen. This suggests the need for additional comparative assessment of the potency and efficacy of these four vaccines in vaccinated subjects.

Hybrid Immunity and SARS-CoV-2 Antibodies: Results of the HEROES-RECOVER Prospective Cohort Study.

There are limited data on whether hybrid immunity differs by count and order of immunity-conferring events (infection with severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] or vaccination against coronavirus disease 2019 [COVID-19]). From a multi-site cohort of frontline workers, we examined the heterogeneity of the effect of hybrid immunity on SARS-CoV-2 antibody levels. Exposures included event count and event order, categorized into 7 permutations. Outcome was level of serum antibodies against receptor-binding domain (RBD) of the ancestral SARS-CoV-2 spike protein (total RBD-binding immunoglobulin). Means were examined up to 365 days after each of the first to seventh events. Analysis included 5793 participants measured from 7 August 2020 to 15 April 2023. Hybrid immunity from infection before 1 or 2 vaccine doses elicited modestly superior antibody responses after the second and third events (compared with infections or vaccine doses alone). This superiority was not repeated after additional events. Among adults infected before vaccination, adjusted geometric mean ratios (95% confidence interval [CI]) of anti-RBD early response (versus vaccinated only) were 1.23 (1.14-1.33), 1.09 (1.03-1.14), 0.87 (.81-.94), and 0.99 (.85-1.15) after the second to fifth events, respectively. Post-vaccination infections elicited superior responses; adjusted geometric mean ratios (95% CI) of anti-RBD early response (versus vaccinated only) were 0.93 (.75-1.17), 1.11 (1.06-1.16), 1.17 (1.11-1.24), and 1.20 (1.07-1.34) after the second to fifth events, respectively. Evidence of heterogeneity in antibody levels by permutations of infection and vaccination history could inform COVID-19 vaccination policy.

Effect of GnRH Active Immunisation on Reproductive Performance of Male Sprague Dawley Rats.

To investigate the effect of active immunisation with gonadotropin-releasing hormone (GnRH) on the reproductive function in male Sprague Dawley (SD) rats, 24 42-day-old rats were randomly assigned to treatment with GnRH6-MAP, GnRH-OVA, a surgical castration group, and a blank control group. Each rat in the treatment groups was intramuscularly injected at 6, 8, and 10 weeks of age. The serum concentrations of testosterone (T), follicle-stimulating hormone (FSH), luteinising hormone (LH), and anti-GnRH antibodies were determined using enzyme-linked immunosorbent assays. The results showed that active immunisation with recombinant GnRH6-MBP and GnRH-OVA significantly increased the serum levels of anti-GnRH antibodies and reduced the serum concentrations of testosterone compared to the black control. Eight weeks after immunisation, the rats' testes were surgically removed for morphological evaluation, showing atrophy of the convoluted vasculature, relative emptying of the lumen, and insignificant differentiation of spermatogonial cells, which were increased in weight and volume compared with the blank control group. These findings indicated that active immunisation with GnRH can lead to testicular atrophy and reduce gonadal hormone concentrations, suggesting that GnRH is a highly effective immunogen.

The Association Between Thyroid Hormones and Renal Function in Euthyroid Chinese Individuals: A Population-Based Cross-Sectional Study.

Objective This population-based cross-sectional study aimed to investigate the association between thyroid hormones and renal function in euthyroid Chinese individuals, as the relationship between thyroid hormones and renal function in this population remains unclear. Methods A total of 661 participants were included in the study after excluding individuals with thyroid diseases, incomplete clinical measurements, or those taking medications affecting thyroid function. Participants were categorized into three groups based on serum thyroid hormone and antibody levels. The study adjusted for covariates and assessed the glomerular filtration rate (GFR) and urine albumin-to-creatinine ratio (ACR) in relation to thyroid hormone levels. Results After adjusting for covariates, the study found a significant increase in GFR in the middle and highest tertiles of free triiodothyronine (FT3) and the highest tertile of total triiodothyronine (TT3). Serum FT3 and TT3 levels were significantly associated with GFR. Additionally, the study observed a significantly lower GFR in the highest tertile of thyroid-stimulating hormone (TSH) compared to the lowest tertile. However, thyroid hormone and antibody levels were not associated with the ACR. Furthermore, the highest tertiles of TT3 and total thyroxine (TT4) were associated with a decreased risk of chronic kidney disease (CKD). Conclusion In our study among euthyroid Chinese individuals, we observed a significant association between thyroid functionand GFR. Specifically, lower FT3, TT3, and higher TSH were associated with reduced GFR, indicating a potential role for thyroid hormones in maintaining renal function. Furthermore, lower levels of TT3and TT4were associated with an increased risk of CKD. These findings suggest a direct link between thyroid and renal function, even in euthyroid individuals, emphasizing the need for further investigation to elucidate the underlying mechanisms and potential therapeutic implications.