Low Antibody Levels Research Articles

Adults with low opsonic natural antibody levels against Streptococcus pneumoniae show enhanced response to PPSV23 vaccination

ABSTRACT Background Pneumococcal diseases pose a significant public health concern globally, particularly among young children and the elderly. Vaccination plays a crucial role in their prevention. This study evaluated the functional immune responses to Pneumococcal polysaccharide vaccine serotypes in healthy Indian adults before and after administering a single dose of PPSV23 immunization. Methods A total of 125 healthy participants aged 18–65 received the PPSV23 vaccine, and their pre- and post-immunization sera were analyzed by MOPA. Opsonic Index, Geometric mean OPA titers and fold increase for each serotype was calculated. Results The highest baseline OPA GMTs were observed for serotypes 33F,17F,9N,20, and 6B. The lowest OPA GMTs were noted against types 1 and 12F. OPA GMTs post-vaccination increased significantly for all serotypes, with geometric mean fold rise (GMFR) ranging from 4.3 to 267.5. Participants with low pre-immunization OPA titers (<8 & <64) showed significant increases in OI fold raise across all tested serotypes post-vaccination. This robust immune response was consistent across serotypes, indicating highly effective seroconversion in individuals with low baseline antibody levels. Conclusion The PPSV23 vaccine elicits a strong immunogenic response in individuals with low pre-immunization OPA titers, achieving substantial increases in opsonic index fold raise across various serotypes.

Monkeypox virus A29L protein as the target for specific diagnosis and serological analysis

The unexpected monkeypox (Mpox) outbreak has been reported in many non-endemic countries and regions since May 2022. The mutant strains of Mpox virus (MPXV) were found with higher infectivity and greater capability for sustained human-to-human transmission, posing a significant public health threat. MPXV A29L, a protein homolog of vaccinia virus (VACV) A27L, plays an important role in viral attachment to host cell membranes. Therefore, MPXV A29L is considered the diagnostic target and the potential vaccine candidate for eliciting neutralizing antibodies and protective immune responses. In response to the escalating Mpox outbreak, three monoclonal antibodies (mAbs) (2-9B, 3-8G, and 2-5H) targeting the different domains of MPXV A29L have been developed in the study. Among them, 2-5H is highly specific for MPXV A29L without exhibiting cross-reactivity with VACV A27L. The antibody pairing composed of 2-5H and 3-8G has been developed as the lateral flow immunochromatographic assay for specific detection of MPXV A29L. However, these three mAbs were unable to inhibit A29L binding to heparin column or prevent MPXV infection in the neutralization test assays. The results of the serological assays using the truncated A29L fragments as the antigens showed that the Mpox patient sera contained significantly lower levels of antibodies targeting the N-terminal 1–34 residues of A29L, suggesting that the N-terminal portion of A29L is less immunogenic upon natural infection.Key points• MAbs 2-9B, 3-8G, and 2-5H neither interrupted A29L binding to heparin nor neutralized MPXV.• The LFIA composed of 3-8G and 2-5H can specifically distinguish MPXV A29L from VACV A27L.• Mpox patient sera contained lower levels of antibodies targeting the N-terminal portion of A29L.

Neutralizing antibody correlate of protection against severe-critical COVID-19 in the ENSEMBLE single-dose Ad26.COV2.S vaccine efficacy trial

Assessment of immune correlates of severe COVID-19 has been hampered by the low numbers of severe cases in COVID-19 vaccine efficacy (VE) trials. We assess neutralizing and binding antibody levels at 4 weeks post-Ad26.COV2.S vaccination as correlates of risk and of protection against severe-critical COVID-19 through 220 days post-vaccination in the ENSEMBLE trial (NCT04505722), constituting ~4.5 months longer follow-up than our previous correlates analysis and enabling inclusion of 42 severe-critical vaccine-breakthrough cases. Neutralizing antibody titer is a strong inverse correlate of severe-critical COVID-19, with estimated hazard ratio (HR) per 10-fold increase 0.35 (95% CI: 0.13, 0.90). In a multivariable model, HRs are 0.31 (0.11, 0.89) for neutralizing antibody titer and 1.22 (0.49, 3.02) for anti-Spike binding antibody concentration. VE against severe-critical COVID-19 rises with neutralizing antibody titer: 63.1% (95% CI: 40.0%, 77.3%) at unquantifiable [<4.8975 International Units (IU)50/ml], 85.2% (47.2%, 95.3%) at just-quantifiable (5.2 IU50/ml), and 95.1% (81.1%, 96.9%) at 90th percentile (30.2 IU50/ml). At the same titers, VE against moderate COVID-19 is 32.5% (11.8%, 48.4%), 33.9% (19.1%, 59.3%), and 60.7% (40.4%, 76.4%). Protection against moderate vs. severe disease may require higher antibody levels, and very low antibody levels and/or other immune responses may associate with protection against severe disease.

Immune history shapes human antibody responses to H5N1 influenza viruses.

Avian H5N1 influenza viruses are circulating widely in cattle and other mammals and pose a risk for a human pandemic. Previous studies suggest that older humans are more resistant to H5N1 infections due to childhood imprinting with other group 1 viruses (H1N1 and H2N2); however, the immunological basis for this is incompletely understood. Here we show that antibody titers to historical and recent H5N1 strains are highest in older individuals and correlate more strongly with year of birth than with age, consistent with immune imprinting. After vaccination with an A/Vietnam/1203/2004 H5N1 vaccine, both younger and older humans produced H5-reactive antibodies to the vaccine strain and to a clade 2.3.4.4b isolate currently circulating in cattle, with higher seroconversion rates in young children who had lower levels of antibodies before vaccination. These studies suggest that younger individuals might benefit more from vaccination than older individuals in the event of an H5N1 pandemic.

Modulatory effects of inorganic mercury (Hg (II)) and lead (Pb (II)) on immune responses of Pekin ducklings (Anas platyrhynchos domesticus) upon a viral-like immune challenge

Trace metal contamination is ubiquitous around the world and may affect the health of wildlife. Divalent trace metals, including ions of mercury (Hg) and lead (Pb), have been shown to be immunotoxic to avian species. However, little is known about the immunomodulatory effects of trace metal exposure on viral infections, especially in young birds, who may be more sensitive. Therefore, the objective of the current study is to provide more insights in the causality between trace metal exposure and the effects of exposure on the immune responses in young waterfowls. Pekin duckling was used as an animal model to investigate the effects of inorganic divalent Hg (II) and Pb (II) on avian immune responses upon a viral-like challenge with double-stranded RNA. Our results indicate that Hg (II) altered the immune gene expression 24 h post-challenge, as reflected by induction of pro-inflammatory genes IL-8, iNOS, TLR3 and TLR7, and a significant decrease of microRNA-155. Ducklings exposed to Pb (II) showed lower levels of natural antibodies, reduced white blood cell counts and lower heterophil proportions 24 h post-challenge. Although inorganic divalent Hg (II) and Pb (II) showed specific differential effects on the immune response of Pekin ducklings, the overall adverse immunomodulatory outcomes in both cases point to inflammation, impaired B-cell function, and weaker immunocompetence.

Infection-Associated Flares in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is characterised by generalised immune dysfunction, including infection susceptibility. Infection-associated flares (IAFs) are common and might rapidly self-resolve, paralleling infection resolution, but their specific clinical phenotype is poorly understood. Therefore, we screened 2039 consecutive visits and identified 134 flares, defined as a loss of the lupus low disease activity state (LLDAS), from 1089 visits at risk spanning over multiple follow-up years, yielding an average yearly LLDAS deterioration rate of 17%. Thirty-eight IAFs were isolated from the total flares and were mostly related to bacterial and herpesvirus infections. When compared to other flares (OFs; n = 98), IAFs showed no milder patterns of organ involvement and similar rates of long-term damage accrual, as estimated by conventional clinimetrics. Arthritis in IAFs was more severe than that in OFs [median (interquartile range) DAS-28 2.6 (2.3-4.1) vs. 2.0 (1.6-2.7); p = 0.02]. Viral IAFs were characterised by atypically lower levels of anti-DNA antibodies (p < 0.001) and possibly abnormally high complement levels when compared to flares of different origin. These data suggest that IAFs are of comparable or even higher severity than OFs and may subtend distinct pathophysiological mechanisms that are poorly tackled by current treatments. Further research is needed to confirm these data.

Clinical Pathology Evaluation in Pet Rabbits Vaccinated Against Rabbit Hemorrhagic Disease Virus 2 (RHDV2).

A recombinant vaccine for rabbit hemorrhagic disease virus 2, a highly pathogenic virus, was granted emergency use authorization in the United States after the detection and spread of the virus starting in 2018. The goal of the current study was to assess pet rabbits (n = 29) through physical examination and routine clinical pathology testing using repeated assessments post-vaccination. In addition, seroconversion was also monitored after the initial vaccination and booster vaccination. Neither owners nor clinicians detected any physical abnormalities in relationship to the vaccine protocol. Hematological and clinical biochemistry testing showed some changes although median values were within species specific reference intervals. A significant increase in antibody levels was observed at day 21 (post-initial vaccination) and day 49 (post-booster vaccination) versus that present at baseline (p < 0.0001). However, variability in study rabbits was noted with some individuals showing low antibody levels as well as a lower overall response in older rabbits (r = -0.56, p = 0.006). A second cohort of rabbits was assessed at 11-12 months post-initial vaccination. In this second group, antibody levels were not significantly different from baseline levels (p = 0.21). Additional studies should be conducted to further define the variability in seroconversion and the term of protection in pet rabbits as the industry moves forward in the optimization of RHDV2 vaccines.

Durable Immune Response and Long-term Efficacy of COVID-19 Vaccination in Children With Inflammatory Bowel Disease.

Children with inflammatory bowel disease (IBD) may have diminished serologic response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and increased risk for subsequent severe coronavirus disease 2019 (COVID-19) infection. We sought to describe outcomes among those who developed SARS-CoV-2 infection following vaccination, characterize SARS-CoV-2 antibodies 1 year post-vaccination, and identify factors associated with durable serologic response. We recruited children with IBD who received ≥2 doses of SARS-CoV-2 vaccine and prospectively collected data on (1) demographics, IBD characteristics, and therapy and (2) SARS-CoV-2 vaccination, testing, and infection symptoms. Serum was obtained for measurement of anti-receptor-binding domain IgG antibodies following a 2-part immunization at 12 and 52 weeks. We enrolled 298 participants (mean age 11.9 ± 3.82, 50% female, 67% Crohn's disease). Symptomatic COVID-19 infection after vaccination occurred in half of the participants, although only 2 (1%) required hospitalization. Anti-tumor necrosis factor alpha (TNF-α) was associated with higher likelihood of symptomatic COVID-19 infection, with an adjusted hazard ratio of 2.7 (95% CI, 1.5-5.0; P = .001). Nearly all participants (99%) had detectable antibody at Week 52. Children aged 1-5 years had lower 52-week antibody level compared to older children (P = .04), as did those on anti-TNF-α therapy (P = .007) and those who received only 2 vaccine doses prior to Week 52 (P < .001). SARS-CoV-2 vaccination provides lasting serologic response and protection against severe COVID-19 for most children with IBD, despite the use of lower vaccine doses in younger children and wide-ranging classes of immunosuppressive therapies.

Evaluation of the Anti-Inflammatory/Immunomodulatory Effect of Teucrium montanum L. Extract in Collagen-Induced Arthritis in Rats.

The anti-inflammatory/immunomodulatory effects of Teucrium montanum L. (TM), a plant distributed in the Mediterranean region, have been insufficiently examined. The effects of the TM ethanol extract were tested in a rat collagen-induced arthritis (CIA) model of rheumatoid arthritis. LC-MS was used for the phytochemical analysis of the TM extract. Dark Agouti rats were immunized with bovine type II collagen (CII) in incomplete Freund's adjuvant for CIA, and treated with 100 or 200 mg/kg of TM extract daily via oral administration. Clinical and histopathological evaluations and a flow cytometric analysis of the phenotypic and functional characteristics of splenocytes and draining lymph node cells were performed. The cytokines in the paw tissue culture supernatants and anti-CII antibodies in serum were determined by ELISA. The TM extract, with the dominant components verbascoside and luteolin 7-O-rutinoside, reduced the arthritic score and ankle joint inflammation in CIA rats, promoted the antioxidant profile in serum, and lowered pro-inflammatory TNF-α, IL-6 and IL-1β production. It suppressed the activation status of CD11b+ cells by lowering CD86, MHCII and TLR-4 expression, and promoted the Th17/T regulatory cell (Tregs) balance towards Tregs. A lower frequency of B cells was accompanied by a lower level of anti-CII antibodies in treated rats. These findings imply the favorable effect of TM extract on the clinical presentation of CIA, suggesting its anti-inflammatory/immunomodulatory action and potential therapeutic effect.

Clustering Analysis Identified Distinct Clinical Phenotypes among Hemodialysis Patients in Their Immunological Response to the BNT162b2 mRNA Vaccine against SARS-CoV-2.

Background: The 2019 coronavirus disease (COVID-19) pandemic induced a major health crisis worldwide, notably among end-stage kidney disease (ESKD) patients. Vaccination against SARS-CoV-2, especially with messenger RNA (mRNA) vaccines, is highly effective and reduces hospitalization and mortality in both the general and ESKD populations. Age and previous COVID-19 infection have been identified as major determinants of the vaccine response in both the general population and ESKD patients. Methods: To determine the specific phenotype of ESKD patients in relation to their vaccine response, a clustering approach was used in a cohort of 117 fully vaccinated patients. Results: Clustering revealed three distinct clinical phenotypes among hemodialysis patients in terms of immunological response. Two clusters, consisting of either women with a long dialysis history or male subjects with diabetes with a moderate history of dialysis, exhibited low levels of IgG anti-spike antibodies. The third cluster consisted of non-diabetic middle-aged men with a moderate dialysis vintage and a very good serological response to vaccination. Conclusions: These vaccinal phenotypes of dialysis patients are easily identifiable in current practice, allowing for differential serological follow-up and tailored booster SARS-CoV-2 vaccination.

Assessment of post-COVID-19 vaccination neutralizing antibodies in kidney transplant and hemodialysis patients versus the general population

Background Patients receiving hemodialysis (HD) and kidney transplant recipients are immunocompromised populations prioritized for coronavirus disease 2019 (COVID-19) vaccination, however, there were few clinical trials with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine responses. Compared with controls, individuals with chronic kidney disease and those on immunosuppressants have lower antibody titers and rates of seroconversion after vaccination. There is a lack of data on their humoral response to COVID-19 immunization. To study the effect of different types of available COVID-19 vaccines in Egypt (AstraZeneca, Sinopharm, Pfizer/BioNTech, and Sputnik) on neutralizing antibodies against COVID-19 in HD and kidney transplantation patients compared with the healthy population. Patients and methods A total of 84 participants; 28 HD patients, 28 kidney transplant recipients, and 28 healthy medical staff members were recruited to test the serological reaction. Six months following the second dose of the COVID-19 vaccine, we evaluated antibody titers against SARS-CoV-2 by Elecsys Anti-SARS-CoV-2 S (Roch) and collected data from the patients, including their comorbidities and the length of time since their kidney transplant. Results All the study groups were comparable as regards age, sex, and BMI, however, hemoglobin was significantly higher in the control group. Antibody response to vaccination was strongest in the control group (100%), followed by HD patients (85%), with transplant recipients showing a significantly weaker response (60%). The Pfizer vaccine generated higher neutralizing antibody levels compared with other vaccines in this study. Yet, the difference was not statistically significant. Additionally, no significant difference in response between the different vaccine types. the transplant group displayed significantly lower levels compared with the control group (P&lt;0.001) and a trend towards lower levels compared with the dialysis group (P=0.06). Conclusion Our study found that all tested vaccines generated comparable levels of neutralizing antibodies in healthy individuals and those with chronic kidney disease (dialysis patients). While 85% of dialysis patients achieved seroconversion (positive antibody test) similar to the healthy control group, only 60% of kidney transplant recipients did. the duration post-transplant may be associated with higher rate of seroconversion. the transplant group displayed lower levels of antibodies compared with the control and the dialysis group which suggests a weaker immune response in transplant patients.

Aging brought additional immune response alterations after breakthrough infections with the Omicron BA.5/BF.7 variants: Protein immune mechanism

The global spread of the Omicron variant strain BA.5/BF.7 has led to an increase in breakthrough infections. The elderly population shows different immune responses after infection due to the aging of the immune system, which has not been fully studied. The aim of this study was to investigate the effect of aging on immune response after breakthrough infection of Omicron BA.5/BF.7 variant, especially the changes of protein immune mechanism. The study analyzed the concentration of antibodies in serum and their ability to neutralize the mutant strain by comparing the immune response of the elderly population and the young population after infection. Proteomics techniques were used to assess differences in the expression of key proteins in immune cells of different age groups. The study found that older subjects produced lower levels of antibodies after infection than younger subjects and showed a significantly reduced ability to neutralize against BA.5/BF.7. In addition, proteomic analysis showed that the expression of proteins related to inflammation and apoptosis significantly increased in the immune cells of the elderly, while the proteins related to antiviral response and cell repair significantly decreased. These findings provide new ideas for immune intervention strategies in the elderly population, and emphasize the targeted research of anti-virus vaccines.

Anti-pentraxin 3 antibodies and residual disease activity in rheumatoid arthritis.

This study quantified anti-PTX3 antibodies in the serum of seropositive and seronegative rheumatoid arthritis (RA) patients, examining their associations with disease activity and patient-reported outcomes (PROMs). In this cross-sectional study, RA patients diagnosed per ACR/EULAR 2010 criteria were recruited. Seronegative RA was defined as ACPA < 7 kU/l. Data on demographics, clinical characteristics, medications, and PROMs were collected. Serum anti-PTX3 antibodies were measured using an in-house ELISA method. Comparative analyses were conducted with historical controls having psoriatic arthritis (PsA) and fibromyalgia (FM). The cohort included 83 RA patients (42 seropositive, 41 seronegative). Seropositive patients had lower anti-PTX3 antibody levels than PsA (p= 0.001) and FM (p= 0.004) controls. Seronegative patients had higher levels than seropositive ones (p= 0.032). Anti-PTX3 antibodies correlated with CDAI (r = 0.255), PtGA (r = 0.257), VAS-GH (r=-0.235), VAS-pain (r = 0.233), and HAQ (r = 0.311), but not with joint counts, inflammatory markers, or physician's global assessment. The PtGA association remained significant when adjusted for BMI, SJC28, ESR, and prednisone dosage (β = 0.206, p= 0.042). Patients with near-controlled RA (SJC28 ≤ 2, PtGA > 2) had higher anti-PTX3 levels than those with controlled disease (SJC28 ≤ 2, PtGA ≤ 2; p= 0.048). Tocilizumab or abatacept-treated patients had lower levels compared with those on TNFi or JAKi. Elevated anti-PTX3 antibodies in RA indicate residual active disease despite controlled inflammation. They may serve as a biomarker for true active disease, especially in seronegative RA patients who might be undertreated.

Long-term immune response and antibody dynamics after SARS-CoV-2 vaccination in patients undergoing renal replacement therapy

Introduction and objective: The SARS-CoV-2 virus has triggered a global pandemic, particularly affecting individuals with comorbidities and those on renal replacement therapy. Vaccination has become a critical strategy, although evidence indicates suboptimal immunity in these groups compared to the general population. Material and methods: The study assessed the post-vaccination response in 121 patients undergoing renal replacement therapy and 104 control individuals. IgG antibody levels against glycoprotein S were measured twice: the first sample was collected 4–8 months after two vaccine doses, and the second sample 6–8 months after third dose. Results: In both groups, antibody titres significantly increased after the third vaccine dose, with no notable difference between the control and study groups after two vaccine doses (p &lt; 0.001). The findings revealed no statistically significant difference in antibody levels between the two groups. Furthermore, there was no significant difference in infection frequency after three vaccine doses (p = 0.072). Patients who contracted COVID-19 after the third vaccination had lower antibody levels during the first blood draw, suggesting a potential impact on immunity. Among dialysis patients, a correlation was found between IgG antibody titres (in the first blood draw) and a longer time interval between the first and second vaccine doses (p = 0.021). The regression analysis indicated that a 1-unit increase in antibody level resulted in a 0.1% reduction in the risk of infection. Conclusions: The results imply that achieving immunity comparable to the general population is possible among patients undergoing renal replacement therapy more than half a year after receiving three vaccine doses. The study also introduces the hypothesis of a delayed antibody response.

Universal All-In-One Lateral Flow Immunoassay with Triple Signal Amplification for Ultrasensitive and Simple Self-Testing of Treponema pallidum Antibodies.

Lateral flow immunoassay (LFIA) is valued for its simplicity and rapidity for on-site screening, however, it experienced false negatives in real sample analysis due to low sensitivity. Although many signal amplification techniques can improve the sensitivity, they usually require additional complicated steps. To address these issues, taking Treponema pallidum (T. pallidum) antibodies as a model detecting target, herein, we report an all-in-one LFIA (AIO-LFIA) with triple-step signal amplification to significantly improve sensitivity while maintaining simplicity. This LFIA utilizes a biotin-streptavidin system for initial signal amplification, followed by introducing a release controller with a specific imprinted structure for timed multicomponent release, which avoids the extra steps when adding components in traditional LFIA. Particularly, a 3D-printed programmed metal in situ growth (MISG) device is integrated to localize signal enhancement at specific sites, overcoming limitations of traditional MISG and substantially reducing reagent usage and assay time, and the nitrocellulose membrane surface was much cleaner than the conventional approach, which facilitates signal readout. After optimization, the proposed AIO-LFIA is capable of visual detection down to 1 pg/mLT. pallidum antibodies in 15 min, 1000-fold lower than the gold nanoparticle-based LFIA. In clinical testing of 152 samples, the AIO-LFIA can distinguish all positive samples, outperforming commercial LFIA which missed those positive samples with relatively low antibody levels. Thus, this study presents a universal ultrasensitive and reliable AIO-LFIA strategy for infectious diseases self-testing, providing an effective promising prospect to address the challenge over emerging infectious diseases in the future.

Immunogenicity of Pneumococcal Polysaccharide Vaccine in patients with rheumatoid arthritis

The presented review searched for articles in the databases PubMed, Web of Science, Scopus, Google Scholar, eLibrary (2002-2022) and assessed the immunogenicity of the 23-valent polysaccharide pneumococcal vaccine (PPV23) in adult patients with rheumatoid arthritis (RA), receiving various antirheumatic drugs. The results of this review indicated sufficient immunogenicity of PPV23 in RA patients receiving monotherapy with various biological drugs (bDMARDs) (TNFα inhibitors, IL6 receptor inhibitors, T-lymphocyte costimulation blockers), targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs), and glucocorticoids (GC) in medium and low doses. Monotherapy with methotrexate (MTX), rituximab and combination therapy with bDMARDs +MTX, tsDMARDs+MTX in RA patients reduced the postvaccination pneumococcal response. IgG AT generated in response to PPV23 injection shown functional activity even in RA patients whose antibodies were either lowered in patients receiving MTX or were not detectable at protective values following bDMARD therapy. The potential for pneumococcus antibody production in RA patients receiving therapy with disease-modifying antirheumatic drugs (DMARDs), tsDMARDs and bDMARDs, was concluded. Vaccination against pneumococcal infection should be advised prior to starting therapy due to the likelihood of low antibody levels developing during rituximab treatment.

Evaluation of commercial quadrivalent foot-and-mouth disease vaccines against east African virus strains reveals limited immunogenicity and duration of protection

Foot-and-mouth disease virus (FMDV) causes a contagious disease (FMD) in cloven-hoofed animals. For FMD-endemic countries, vaccination is critical for controlling disease but is rarely monitored, despite substantial funds spent on vaccine purchases. We evaluated antibody responses in cattle to two commercial vaccines each containing antigens of four FMDV serotypes. Sampling was done over 360 days, with serology for each serotype performed using commercially available solid phase competition ELISAs (SPCE) and with virus neutralization tests (VNT) employing regionally relevant test viruses. A primary course of each vaccine was administered to 37 calves, some of which received a second dose after 28 days. Using new production batches of vaccines, all calves received a booster vaccination 180 days post vaccination, while 10 additional naïve calves were also vaccinated using the new batches and followed up for ∼180 days. Simple and general linear models were used to compare antibody responses which varied substantially according to vaccine, dose regime, serotype, and test, but were mostly insufficient to ensure a high likelihood of adequate or sustained probable protection. One of the vaccines administered as a two-dose primary course of vaccination was superior to other options, but even then, data trajectories from VNT responses suggested probable protection of 75 % of calves for 6 months for only one virus serotype. Calves administered with the other vaccine and those given a single primary dose developed low levels of antibodies, offering predicted likely protection lasting less than two months. Individual SPCE results were weakly correlated (r2 = 0.48) to neutralization and associated likelihoods of protection but SPCE and VNT agreed on which vaccine and dose regime performed best. Our findings highlight gaps in immunogenicity of FMD vaccines used in East Africa and reinforce the importance of independent quality control studies to evaluate and improve commercial FMD vaccines and vaccination regimes.

Progranulin mediates the onset of pristane induced systemic lupus erythematosus

BackgroundsProgranulin (PGRN) is a growth factor-like molecule with diverse roles in homeostatic and pathogenic processes including the control of immune and inflammatory responses. Pathogenic inflammation is a hallmark of systemic lupus erythematosus (SLE) and elevated serum levels of PGRN has been evaluated as a biomarker of disease activity in SLE. However, the role of PGRN in SLE has not been fully investigated. This study is aimed to determine the potential involvements of PGRN in SLE.MethodsWild type (WT) and PGRN knockout (PGRN-/-) C57BL/6 mice received intraperitoneal injection of pristane for induction of a murine model of SLE. Sera were collected every biweekly and levels of anti-dsDNA antibody, IgG, and inflammatory factors were measured. Mice were sacrificed 5 months later and the renal lesions, as well as the proportions of T cell subtypes in the spleen were analyzed.ResultsFollowing exposure to pristane, PGRN-/- mice generated significantly lower levels of anti-dsDNA antibody and IgG relative to WT mice. PGRN-/- mouse kidneys had less IgG and collagen deposition compared with WT mice after pristane injection.ConclusionThe results indicate that PGRN participates in inflammatory response and renal damage in pristane induced SLE models, suggesting that PGRN mediates the onset of SLE.

Detection and comparison of SARS-CoV-2 antibody produced in naturally infected patients and vaccinated individuals in Addis Ababa, Ethiopia: multicenter cross-sectional study

BackgroundNatural infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or vaccination triggers antibody production against key viral antigens. However, there is limited evidence on the levels of antibodies produced in naturally infected individuals compared to those vaccinated in Ethiopia. Therefore, we aimed to detect and compare SARS-CoV-2 antibodies produced by naturally infected and vaccinated individuals.Materials and methodsWe conducted a multicenter cross-sectional study among a total of 355 naturally infected and 355 vaccinated individuals from November 2022 to April 2023 at 10 selected health facilities in Addis Ababa, Ethiopia. We enrolled the participants consecutively upon their arrival at health facilities until the required sample size was achieved. We used a structured questionnaire to collect data on the demographic and clinical characteristics of the participants. We also collected 3–5 ml of blood samples from all participants and tested for anti-Spike (anti-S) and anti-nucleocapsid (anti-N) antibodies using Cobas 6000. We utilized frequency, mean, or median to describe the data, the Mann-Whitney U test to compare groups, and a generalized linear regression model to assess factors associated with anti-S antibody concentration. We analyzed the data with SPSS version 26, and the level of significance was set at P-value < 0.05.ResultsOf the naturally infected participants, 352 (99.5%) had anti-S antibodies and all (100%) had anti-N antibodies, whereas among vaccinated participants, all (100%) had anti-S antibodies, while 323 (91.6%) had anti-N antibodies. Anti-S antibodies produced by vaccinated individuals were significantly (P < 0.001) higher than those produced as a result of natural infection. Being young (P = 0.004), having hypertension (P < 0.001), and having diabetes (P < 0.001) were significantly associated with lower anti-S antibody levels, while being recently vaccinated and having a higher number of vaccine doses were significantly associated with higher anti-S antibody concentrations in vaccinated participants. Having diabetes (P < 0.001) were significantly associated with lower anti-S concentrations in participants who were naturally infected.ConclusionThere is a high seropositivity rate in both naturally infected and vaccinated individuals. However, vaccinated individuals had higher levels of SARS-CoV-2 antibodies than those who were naturally infected, which highlights the significant contribution of vaccination in increasing the protection of COVID-19 in Ethiopia.

Sex-based difference in immune responses and efficacy of the pneumococcal conjugate vaccine.

Vaccine-mediated protection and susceptibility to Streptococcus pneumoniae (pneumococcus) infections are influenced by biological sex. The incidence of invasive pneumococcal disease remains higher in males compared to females even after the introduction of the pneumococcal conjugate vaccine (PCV). However, sex-based differences in the immune response to this conjugate vaccine remain unexplored. To investigate those differences, we vaccinated adult male and female mice with PCV and assessed cellular and humoral immune responses. Compared to females, male mice displayed lower levels of T follicular helper cells, germinal center B cells and plasmablasts, which are all required for antibody production following vaccination. This was linked to lower IgG and IgM levels against pneumococci and lower isotype switching to IgG3 in vaccinated males. Due to lower antibody levels, sera of vaccinated male mice had lower efficacy in several anti-pneumococcal functions including neutralization of bacterial binding to pulmonary epithelial cells as well as direct cytotoxicity against S. pneumoniae. Importantly, while the vaccine was highly protective in females, vaccinated males succumbed to infection more readily and were more susceptible to both lung-localized infection and systemic spread following S. pneumoniae challenge. These findings identify sex-based differences in immune responses to PCV that can inform future vaccine strategies.