Positive Antibody Response Research Articles

The Long-Term Characteristics of Immunity Conferred by COVID-19 Using Antibody Tests.

IntroductionSince December 2019, more than 184 Million cases and 3.97 Million COVID-19 related deaths have been reported around the world. Since these statistics are laboratory-based confirmed cases, the true burden of disease may be underestimated. Many populations like those who are regularly visiting health care facilities and those with end-stage renal disease (ESRD) for visiting dialysis units, patients with malignancies, on regular chemo and radiotherapy, and healthcare workers (HCW) are considered high risk for nosocomial COVID-19 re-infections.ObjectiveTo understand the long-term behaviour and protective efficacy of already formed anti-SARS-CoV-2 antibody against spike-S protein and nucleocapsid antigen in different populations keeping in view their risk of re-exposure and re-infection is high. To delineate seropositivity with respect to age, gender, and other co-morbidities like diabetes mellitus (DM), hypertension (HTN), and chronic kidney disease (CKD)/ESRD as well as the general population.MethodologyDuring the study, 480 cases of COVID-19 with a post-exposure antibody reactive were followed. These patients were followed on telemedicine for the development of reinfection symptoms and persistence of antibody response. Around 115 patients agreed for regular monitoring of their immunity against the COVID-19 virus through testing through the anti-SARS-CoV-2 antibody test. The rest of the patients were followed on telemedicine until the date of development of any re-infection, but none reported to have typical symptoms of COVID-19 along with positive polymerase chain reaction (PCR).ResultsAmong 115 patients, the mean age was 42.44 + 15.755 years. 61.7% of patients were males and 66.1% were non-health workers while 26.1% of patients had DM/HTN or both. Among these patients, 76.5% had mild/no symptoms and antibodies were found present among 51.3% patients for 3-6 months. Only 2.6% of patients were re-infected. Significant association (p<0.05) of age was found with re-infection while insignificant association (p>0.05) of sex, co-morbidities, profession, symptoms, and persistence of antibodies with re-infection.ConclusionThe study concluded that natural immune response was adequate to protect against reinfection as long as more than 9 months. It was more pronounced among patients with ESRD and those with severe disease. Surprisingly, among patients with haematological malignancies, either there was no seropositivity or a very weak positive antibody response. All other malignancies had similar seropositivity behaviour compared to the general population or other co-morbidity like DM, HTN, and coronary artery disease (CAD).

Characterization of humoral response to COVID mRNA vaccines in multiple sclerosis patients on disease modifying therapies

Little is known about COVID-19 mRNA vaccine humoral immune responses in patients with central nervous system autoimmune demyelinating diseases, multiple sclerosis (MS) and neuromyelitis optica (NMO), who are on B-cell depleting therapies (BCDT) and other disease modifying therapies (DMTs). We conducted a single center prospective study to identify the clinical and immunological features associated with vaccine-induced antibody response in 53 participants before and after COVID-19 mRNA vaccination. This is the first report on the anti-spike RBD and anti-nucleocapsid antibody response, along with pre- and post-vaccine absolute lymphocyte counts (ALC) and flow cytometry analysis of CD19 and CD20 lymphocytes in patients with MS and NMO. We tested the hypothesis that patients on BCDT may have impaired COVID-19 vaccine humoral responses. Among patients on BCDT, 36.4% demonstrated a positive antibody response to spike RBD, in comparison to 100% in all other groups such as healthy controls, untreated MS, and patients on non-B cell depleting DMTs (p < 0.0001). Immunological data revealed lower baseline (pre-vaccination) levels of IgM in patients on BCDT (p = 0.003). Low CD19 and CD20 counts and a shorter interval from the last B cell depleting therapy infusion to the first vaccine dose were associated with a negative spike RBD antibody response (non-seroconverter) in patients on BCDT. Age, body mass index (BMI) and total treatment duration did not differ between seroconverters and non-seroconverters.

Third dose of the BNT162b2 vaccine in heart transplant recipients: Immunogenicity and clinical experience

BACKGROUNDThe repeated waves of the COVID-19 pandemic have highlighted the necessity to optimize vaccine responses in immunocompromised populations. We investigated the safety and immunogenicity of a third, booster, dose of the Pfizer BNT162b2 vaccine in heart transplant (HT) patients.METHODSThe cohort comprised 96 adult HT patients who received a third homologous dose of the BNT162b2 vaccine 168 days after the second dose. The vaccine-induced antibody responses of both receptor-binding domain (RBD) IgG and neutralizing antibodies were assessed in all patients, with a positive antibody response being defined as the presence of either IgG anti-RBD or neutralizing antibodies. For a subset of patients, T cell response was also studied.RESULTSThe third dose was associated with a low rate of adverse events, mostly mild pain at the injection site. No serious adverse events were recorded, and there were no episodes of rejection. At 18 days following the third dose of the vaccine, the positive antibody response increased from 23% to 67%, with a corresponding increase in neutralizing capacity. The third dose elicited SARS-CoV-2 neutralization titers >9-fold and IgG anti-RBD antibodies >3-fold of the range achieved after the two primary doses. Mycophenolate use, lower eGFR and higher C-reactive protein were independently associated with a reduced likelihood of generating an immune response. Importantly, a specific T-cell response following the third dose was evident in the majority of transplant recipients.CONCLUSIONSAn homologous third booster dose of the BNT162b2 vaccine gave overall consistent tolerability and a good safety profile, while eliciting humoral and cellular immune responses.

Serological Response to the BNT162b2 COVID-19 mRNA Vaccine in Adolescent and Young Adult Kidney Transplant Recipients.

Background.Initial reports in adult kidney transplant recipients (KTR) indicate low immunogenicity after 2 doses of the BNT162b2 COVID-19 mRNA vaccine. We describe the immunogenicity of this vaccine compared to the serologic response in naturally infected COVID-19 positive adolescent and young adult KTR.Methods.For this prospective observational study, the study group included 38 KTR who received 2 doses of the tested vaccine, and the control group included 14 KTR who had a previous polymerase chain reaction–confirmed COVID-19 infection.Results.The mean age was 18 ± 3 y. Positive serologic responses were observed in 63% and 100% of the study and control groups, respectively (P = 0.01). Antibody titers were almost 30-fold higher in the control than the study group (median [interquartile range (IQR)]: 2782 [1908–11 000] versus 100.3 [4.7–1744] AU/mL, P < 0.001), despite the longer time from the COVID-19 infection to serologic testing compared to time from vaccination (median [IQR]: 157.5 [60–216] versus 37 [20.5–53] d, P = 0.011). Among vaccinated patients, higher proportions of those seronegative than seropositive were previously treated with rituximab (50% versus 8%, P = 0.01). Time from the second vaccine dose to serologic testing was longer in seropositive than seronegative patients (median [IQR]: 24.5 [15–40] versus 46 [27–56] d, P = 0.05). No patient developed symptomatic COVID-19 disease postvaccination.Conclusions.The BNT162b2 COVID-19 mRNA vaccine yielded higher positive antibody response in adolescent and young adult KTR than previously reported for adult KTR. Antibody titers after vaccination were significantly lower than following COVID-19 infection. Longer time may be required to mount appropriate humoral immunity to vaccination in KTR.

Non-COVID Health Care Workers with Positive Antibody Responses: Are We Heading Towards Herd Immunity?

Background: Antibody testing against SARS-CoV-2 complimentary to RT-PCR could be an effective method for its detection. Development of immunity against COVID-19 in context of reinfection and herd immunity still remains debatable and needs further elucidation. The present study was conducted to investigate the immunity status against SARS-CoV-2 in terms of IgG antibody positivity in health care workers at a tertiary care center. Methodology: This single center study was conducted at a tertiary care center, that involved 1039 healthcare workers and other staff members. The testing of all subjects was performed using ELIFAST (SARS-CoV-2 IgG ELISA) kits. The sample population was then segregated into RT-PCR positive and negative/status unknown groups. Groups were further segregated on the basis of IgG positivity status and the sensitivity and specificity was also calculated. Results: Among the 1039 enrolled subjects, 179 (17.23%) were RT-PCR positive for SARS-CoV-2 positive and remaining were either RT-PCR negative or status unknown cases. Among 179 COVID-19 recovered subjects, 19 (10.61%) were negative for IgG, whereas 160 (89.39%) came out IgG positive. Out of 860 (82.77%) RT-PCR Negative/Status unknown, 248 (28.84%) came out IgG positive and the remaining 612 (71.16%) were negative for IgG. The overall sensitivity and specificity were 89.39 and 71.16, respectively. Conclusion: A combined approach of testing for COVID-19 using RT-PCR and rapid antibody assays could be more beneficial. Serological studies project a higher antibody response in population that compel us to think about plausibility of herd immunity. However, variability in serological response could be affected by several factors and the underlying complex immune process of COVID-19 is yet to be fully understood.

Febrile palpebral edema

Febrile palpebral edema

CORRELATION BETWEEN THE ANTIBODY RESPONSE TOWARD SPECIFIC HCV PROTEINS AND HCV VIRAL LOAD

Background: Hepatitis C virus (HCV) is an RNA virus causing acute or chronic infection and affecting more than 2% of population worldwide. The firstline tests for diagnosis of HCV infection are 3rd or 4th generation enzyme immunoassays - ELISA and CIA. They indicate the presence of antibodies against HCV in serum. These tests are characterized by high sensitivity and specificity, but they cannot distinguish past, acute or chronic infection, and sometimes produce false positive results. Confirmatory tests, such as recombinant immunoblot-line immune assay (LIA), and quantitative PCR, are used to validate the positive antibody response. The recombinant immunoblot assay can be used to determine the specificity of antibody to HCV. The aim of the present study is to determine the correlation between the anti-HCV response in confirmatory immunoblot assay and the HCV viral load, measured by PCR. Materials and methods: Twenty-nine anti-HCV positive sera were included in the study. Third generation ELISA assay was used for anti-HCV screening of the samples and for detection of anti-HCV antibodies against specific HCV proteins. Third generation line immunoassay INNO-LIA HCV Score, based on the principle of an enzyme immunoassay, was used as a confirmatory test. The HCV viral load was measured by quantitative PCR method – Abbott Real Time HCV (Abbott Molecular Inc., USA) with linear sensitivity range from 1.08 Log 10 IU/ml (12 [IU/ml]) to 8.00 Log 10 IU/ml (100 000 000 [IU/ml]). Results: HCV RNA was quantified in all studied samples. Ten of 29 serum samples (34%, Group I) were HCV RNA negative. The rest of the samples were HCV RNA positive as follows: 3 serums were with minimal viral load from &lt; 12 to 10 000 IU/ml (10%, Group II); 3 serum samples –between 10 000 and 100 000 IU/ml (10%, Group III); 10 serum samples – between 100 000 and 1 000 000 IU/ml (34%, Group IV) and in 3 serum samples HCV RNA concentration was over 1 000 000 IU/ml (10%, Group V). Conclusion: HCV screening strategies involving anti-HCV detection by ELISA combined with recombinant immunoblot assay can be the method of choice in laboratories with limited equipment and finances.

Salmonella Dublin associated with abortion in dairy cattle in Algiers and comparison of different diagnostic methods

Background: In cattle, many serotypes of Salmonella enterica are responsible for a wide variety of clinical manifestations, which can cause considerable economic loss. Some serotypes can cause cows to abort sporadically, such as the Dublin serotype. This study was carried out on different cattle farms in the Algiers region to determine the prevalence of Salmonella Dublin using bacteriological and immunological methods.Methodology: The prevalence of Salmonella was determined by bacteriological analysis in accordance with the reference method AFNOR NF U 47-100 on faecal samples collected from 184 cattle belonging to 19 different farms, and serotyping for S. Dublin. Immunological analysis by enzyme-linked immunosorbent assay (ELISA) for S. Dublin was carried out on milk samples collected from 91 cattle. A survey of case (n=5) and control (n=14) farms for comparative analysis was performed to demonstrate a link between abortion in cows and prevalence of S. Dublin with both bacteriological and immunological methods. Sensitivity, specificity, Cohen Kappa coefficient, McNemar test odds ratios, and confidence intervals were calculated using Winepiscope 2.0 and StatA 9.1 software,and p&lt;0.05 was considered as statistically significant.Results: The bacteriological results showed a prevalence of 7.6% (95%CI: 3-10), for Salmonella and serotyping revealed a prevalence for S. Dublin of 2.7%. The immunological analysis of milk by the ELISA technique revealed a prevalence of 13.2% (95%CI: 5-20) for S. Dublin. The comparative study between immunological results from milk and bacteriological results from faeces for detecting S. Dublin showed poor agreement between the two tests (k=0.25), with enzyme immunoassay being significantly more sensitive than the bacteriological test (p&lt;0.05). The results of the survey did not demonstrate a clear association between bacteriological detection of S. Dublin in faeces and abortion in cows (OR=8.66, 95%CI: 0.58-130.12). However, with the immunological analysis of milk for S. Dublin, there was a significant positive association (OR=62.33, 95%CI: 2.13-18.22) between a positive antibody response to S. Dublin in milk and the presence of abortions on the farm.Conclusion: In view of these results, we can conclude that Salmonella infections should systematically feature in the differential diagnosis of abortions in dairy cattle in Algeria.&#x0D; Keywords: S. Dublin, cattle, faeces, milk, abortion, immunology, bacteriology, Algiers

Serological surveillance of SARS-CoV-2: Six-month trends and antibody response in a cohort of public health workers

BackgroundAntibody waning after SARS-CoV-2 infection may result in reduction in long-term immunity following natural infection and vaccination, and is therefore a major public health issue. We undertook prospective serosurveillance in a large cohort of healthy adults from the start of the epidemic in England.MethodsClinical and non-clinical healthcare workers were recruited across three English regions and tested monthly from March to November 2020 for SARS-CoV-2 spike (S) protein and nucleoprotein (N) antibodies using five different immunoassays. In positive individuals, antibody responses and long-term trends were modelled using mixed effects regression.FindingsIn total, 2246 individuals attended 12,247 visits and 264 were seropositive in ≥ 2 assays. Most seroconversions occurred between March and April 2020. The assays showed > 85% agreement for ever-positivity, although this changed markedly over time. Antibodies were detected earlier with Abbott (N) but declined rapidly thereafter. With the EuroImmun (S) and receptor-binding domain (RBD) assays, responses increased for 4 weeks then fell until week 12–16 before stabilising. For Roche (N), responses increased until 8 weeks, stabilised, then declined, but most remained above the positive threshold. For Roche (S), responses continued to climb over the full 24 weeks, with no sero-reversions. Predicted proportions sero-reverting after 52 weeks were 100% for Abbott, 59% (95% credible interval 50–68%) Euroimmun, 41% (30–52%) RBD, 10% (8–14%) Roche (N) < 2% Roche (S).InterpretationTrends in SARS-CoV-2 antibodies following infection are highly dependent on the assay used. Ongoing serosurveillance using multiple assays is critical for monitoring the course and long-term progression of SARS-CoV-2 antibodies.

COVID-19 in Autoinflammatory Diseases with Immunosuppressive Treatment.

COVID-19 disease increases interleukin (IL)-1β release. Anti-IL-1-treatment is effective in IL-1-mediated autoinflammatory diseases (AID). This case series presents COVID-19 in patients with IL-1-mediated and unclassified AID with immunosuppressive therapy (IT). Patient 1 is a 34-year-old woman with an unclassified AID and methotrexate. Patients 2 and 3 (14-year-old girl and 12-year-old boy, respectively) have a Cryopyrin-Associated Periodic Syndrome (NLRP3 p.Q703K heterozygous, CAPS) treated with canakinumab 150 mg/month since three and five years, respectively. Patient 4 is a 15-year-old girl who has had familial Mediterranean fever (MEFV p.M694V homozygous) for 3 years treated with canakinumab 150 mg/month and colchicine. All patients had a mild acute COVID-19 course, particularly the adolescent patients. A few weeks after COVID-19 recovery, both CAPS patients developed increased AID activity, necessitating anti-IL-1-treatment intensification in one patient. At day 100, one out of four patients (25%) showed positive antibody response to SARS-CoV-2. This is one of the first reports providing follow-up data about COVID-19 in AID. The risk for severe acute COVID-19 disease was mild/moderate, but increased AID activity post-COVID-19 was detected. Follow-up data and data combination are needed to expand understanding of COVID-19 and SARS-CoV-2 immunity in AID and the role of IT.

Investigations on the occurrence of tapeworm infections in German horse populations with comparison of different antibody detection methods based on saliva and serum samples

BackgroundEffective and sustainable worm control in horses would benefit from detailed information about the current regional occurrence of tapeworms. Different diagnostic methods are currently available to detect Anoplocephala spp. infections in horses. However, the format as well as the sensitivity and specificity of the methods vary considerably.MethodsA coprological, serological and questionnaire study was conducted to investigate the prevalence and risk factors of tapeworm infections on 48 horse farms in the region of Berlin and Brandenburg, Germany. In total, faecal samples of 484 horses were analysed using the double centrifugation/combined sedimentation-flotation and mini-FLOTAC. Serum (n = 481) and saliva (n = 365) samples were analysed by ELISAs to determine antibody levels against Anoplocephala spp. 12/13 kDa excretory/secretory (E/S) antigens.ResultsCestode eggs were detected in 0.6% of faecal samples (farm prevalence 6.3%) without differences between the two methods. In contrast, antibodies against Anoplocephala spp. were detected in 16.2% (farm prevalence 52.1%) and in 29.5% (farm prevalence 75.7%) of the serum and saliva samples, respectively. Both ELISA based methods for detection of tapeworms reported a greater number of infected animals requiring treatment than were positively identified by coproscopy. Logistic regression analysis identified permanent pasture access, large pastures and regular pasture changes and high strongyle egg counts as risk factors for positive serum antibody responses to Anoplocephala spp. while last treatment with praziquantel was protective. Other protective factors were the presence of foals and high numbers of horses on the farm. Daily removal of faeces from the pasture and horse age did not have a significant effect.ConclusionsThe findings of the present serological investigation indicate that tapeworm prevalence in Berlin/Brandenburg horse farms is much higher than would be anticipated by using conventional/coproscopic analyses. Moreover, the majority of tapeworm-positive horses had not received a cestocidal drug at their last treatment. Considering the already known low sensitivity of the coproscopic detection, the equine veterinary diagnostics can be enhanced by the use of antibody detection methods such as the saliva-based ELISA.

Efficient Removal of Non-Structural Protein Using Chloroform for Foot-and-Mouth Disease Vaccine Production.

To differentiate foot-and-mouth disease (FMD)-infected animals from vaccinated livestock, non-structural proteins (NSPs) must be removed during the FMD vaccine manufacturing process. Currently, NSPs cannot be selectively removed from FMD virus (FMDV) culture supernatant. Therefore, polyethylene glycol (PEG) is utilized to partially separate FMDV from NSPs. However, some NSPs remain in the FMD vaccine, which after repeated immunization, may elicit NSP antibodies in some livestock. To address this drawback, chloroform at a concentration of more than 2% (v/v) was found to remove NSP efficiently without damaging the FMDV particles. Contrary to the PEG-treated vaccine that showed positive NSP antibody responses after the third immunization in goats, the chloroform-treated vaccine did not induce NSP antibodies. In addition to this enhanced vaccine purity, this new method using chloroform could maximize antigen recovery and the vaccine production time could be shortened by two days due to omission of the PEG processing phase. To our knowledge, this is the first report to remove NSPs from FMDV culture supernatant by chemical addition. This novel method could revolutionize the conventional processes of FMD vaccine production.

Correlation of clinical outcome with laboratory parameters in children with dengue infection: An appraisal from a tertiary children’s hospital in India

Introduction: Dengue infection is caused by the dengue virus (arbovirus), the incidence of which is increasing in India. In dengue endemic settings, early diagnosis and monitoring for complications are important, especially in children. Concurrent testing of NSI antigen, dengue specific IgG and IgM will help to diagnose patients with suspected dengue fever. Objective: To correlate the clinical profile and outcome of dengue fever with detection of NSI antigen, dengue specific IgG and IgM antibody, hematological and biochemical parameters and blood component utilization. Methods: All children presenting to Rainbow hospital and diagnosed with dengue infection using NS1 and dengue specific IgG and IgM antibody during a one year period (1st November 2016 to 31st October 2017) were included in the study. The haemogram and biochemistry parameters were done using automated analyzers. Inpatients were classified as severe or non-severe based on clinical and/or laboratory evidence. The degree of association between clinical parameters and disease severity in relation to NS1 positivity was expressed as an odds ratio. Results: Among 213 children diagnosed, 126 were treated as inpatients and the rest as outpatients. The age range of the study sample was 6 months to 15 years. NS1 positivity was observed in 72.3 % patients. NS1 positivity, when compared to severity of disease was significant (Odds ratio: 2.3; p Conclusions: Using all three tests (NS1, dengue specific IgM and IgG) was useful, as in 59 (27.7%) patients, despite a negative NS1, based on a positive dengue antibody response (IgG and/or IgM), the patients were admitted and monitored. NS1 positivity was associated with a higher risk of thrombocytopenia in this study.

Results of a randomized, double-blind phase II clinical trial of NY-ESO-1 vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in participants with high-risk resected melanoma

BackgroundTo compare the clinical efficacy of New York Esophageal squamous cell carcinoma-1 (NY-ESO-1) vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in a randomized, double-blind phase II study in participants with...

Prime-boost vaccination strategy enhances immunogenicity compared to single pneumococcal conjugate vaccination in patients receiving conventional DMARDs, to some extent in abatacept but not in rituximab-treated patients

ObjectiveTo explore whether a prime-boost vaccination strategy, i.e., a dose of pneumococcal conjugate vaccine (PCV) and a dose of 23-valent polysaccharide vaccine (PPV23), enhances antibody response compared to single PCV dose in patients with inflammatory rheumatic diseases treated with different immunosuppressive drugs and controls.MethodsPatients receiving rituximab (n = 30), abatacept (n = 23), monotherapy with conventional disease-modifying antirheumatic drugs (cDMARDs, methotrexate/azathioprine/mycophenolate mofetil, n = 27), and controls (n = 28) were immunized with a dose PCV followed by PPV23 after ≥ 8 weeks. Specific antibodies to 12 serotypes included in both vaccines were determined using a multiplex microsphere immunoassay in blood samples before and 4–8 weeks after each vaccination. Positive antibody response was defined as ≥ 2-fold increase from pre- to postvaccination serotype-specific IgG concentration and putative protective level as IgG ≥ 1.3 μg/mL. The number of serotypes with positive antibody response and IgG ≥ 1.3 μg/mL, respectively, after PCV and PCV + PPV23 were compared within each treatment group and to controls. Opsonophagocytic activity (OPA) assay was performed for serotypes 6B and 23F.ResultsCompared to single-dose PCV, prime-boost vaccination increased the number of serotypes with positive antibody response in patients with abatacept, cDMARDs, and controls (p = 0.02, p = 0.01, and p = 0.01), but not in patients on rituximab. After PCV + PPV23, the number of serotypes with positive antibody response was significantly lower in all treatment groups compared to controls but lowest in rituximab, followed by the abatacept and cDMARD group (p < 0.001). Compared to PCV alone, the number of serotypes with putative protective levels after PCV + PPV23 increased significantly only in patients in cDMARDs (p = 0.03) and controls (p = 0.001). Rituximab treatment was associated with large reduction (coefficient − 8.6, p < 0.001) and abatacept or cDMARD with moderate reductions (coefficients − 1.9 and − 1.8, p = 0.005, and p < 0.001) in the number of serotypes with positive antibody response to PCV + PPV23 (multivariate linear regression model). OPA was reduced in rituximab (Pn6B and Pn23F, p < 0.001), abatacept (Pn23F, p = 0.02), and cDMARD groups (Pn6B, p = 0.02) compared to controls.ConclusionsPrime-boost strategy enhances immunogenicity compared to single pneumococcal conjugate vaccination in patients with inflammatory rheumatic diseases receiving cDMARDs, to some extent in abatacept but not in patients on rituximab. Pneumococcal vaccination should be encouraged before the initiation of treatment with rituximab.Trial registrationClinicalTrials.gov, NCT03762824. Registered on 4 December 2018, retrospectively registered

Persistence of vaccine-elicited immune response up to 14 years post-HIV gp120-NefTat/AS01B vaccination

BackgroundVaccines eliciting protective and persistent immune responses against multiple human immunodeficiency virus type 1 (HIV-1) clades are needed. This study evaluated the persistence of immune responses induced by an investigational, AS01-adjuvanted HIV-1 vaccine as long as 14 years after vaccination. MethodsThis phase I, open-label, descriptive, mono-centric, extension study with a single group (NCT03368053) was conducted in adults who received ≥3 doses of the clade B gp120-NefTat/AS01B vaccine candidate 14 years earlier in a previous clinical trial (NCT00434512). Binding responses of serum antibodies targeting a panel of envelope glycoproteins, including gp120, gp140 and V1V2-scaffold antigens and representative of the antigenic diversity of HIV-1, were measured by binding antibody multiplex assay (BAMA). The gp120-specific CD4+/CD8+ T-cell responses were assessed by intracellular cytokine staining assay. ResultsAt Year 14, positive IgG binding antibody responses were detected in 15 out of the 16 antigens from the BAMA V1V2 breadth panel, with positive response rates ranging from 7.1% to 60.7%. The highest response rates were observed for clade B strain V1V2 antigens, with some level of binding antibodies against clade C strains. Anti-V1V2 IgG3 response magnitude breadth, which correlated with decreased risk of infection in a previous efficacy trial, was of limited amplitude. Response rates to the antigens from the gp120 and gp140 breadth panels ranged from 7.7% to 94.1% and from 15.4% to 96.2% at Year 14, respectively. Following stimulation with gp120 peptide pool, highly polyfunctional gp120-specific CD4+ T-cells persisted up to Year 14, with high frequencies of CD40L tumor necrosis factor alpha (TNF-α), CD40L interleukin-2 (IL-2), CD40L TNF-α IL-2 and CD40L interferon gamma (IFN-γ) TNF-α IL-2 CD4+ T-cells, but no CD8+ T-cells detected. ConclusionsPersistent antibodies binding to HIV-1 envelope glycoproteins, including the V1V2-scaffold, and gp120-specific cellular immunity were observed in volunteers vaccinated 14 years earlier with the gp120-NefTat/AS01B vaccine candidate.

Update on immunogenicity in severe asthma: Experience with mepolizumab

Update on immunogenicity in severe asthma: Experience with mepolizumab

Nucleocapsid protein-specific IgM antibody responses in the disease progression of severe fever with thrombocytopenia syndrome

ObjectivesSevere fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that is caused by the SFTS virus (SFTSV) and has a high fatality rate. SFTSV-specific antibody profiles among patients with different clinical outcomes are yet to be described. The nucleocapsid protein (NP) is the most immunogenic viral antigen of the SFTSV. This study, therefore, sought to determine NP-specific antibody responses among SFTS patients with different disease progressions. MethodsIn the present study, 43 patients with confirmed SFTS were enrolled in our cohort, and 9 of them deceased. The clinical presentations and key laboratory parameters associated with SFTS fatality were also recorded. Serum samples from each patient were collected every 2 days during their hospitalization. NP-specific IgM and IgG responses as well as Gn or Gc-specific IgM responses were examined by enzyme-linked immunosorbent assay (ELISA), whereas, the dynamic viral loads of SFTSV RNA were quantified via real-time reverse transcription polymerase chain reaction (RT-PCR). ResultsFirst, 77% of patients generated positive NP-specific IgM antibody responses within two weeks since illness onset, defined as ‘N-specific IgM-positive patients’, while the rest of the patients were termed as ‘N-specific IgM-delayed patients’. Only 17% of the patients generated NP-specific IgG responses. The absence of NP-specific humoral responses was strongly associated with a high risk of fatality and severity of SFTS. IgM-positive patients had significantly lower levels of viral loads, less disturbed coagulopathy, and hepatic and cardiac damage compared to IgM-delayed patients. Moreover, compared to severe or fatal SFTS patients, mild SFTS patients had significantly higher magnitudes of NP-specific IgM responses, but not NP-specific IgG, Gn-specific IgM, or Gc-specific IgM responses. The abundance of NP-specific IgM responses negatively correlated with viral loads, coagulation disturbances, and hepatic injuries among SFTS patients. ConclusionsOur data highlight distinct humoral profiles of NP-specific IgM responses among SFTS patients with different disease progressions and clinical outcomes.

Peste des Petits Ruminants (PPR) virus serological surveillance in goats in Lao PDR: Issues for disease eradication in a low-resource disease-free setting.

Peste des Petits ruminants (PPR) is an economically important transboundary viral disease of goats. This study aimed to determine a baseline of serological evidence for Peste des petits ruminants virus (PPRV) in Lao goats. A total of 1,072 serum samples were collected by convenience sampling across five provinces in Laos and tested for antibody response to PPRV using a commercially available competitive ELISA. Positive antibody responses were found in 2.2% (95% CI 1.4, 3.2) of the samples. True prevalence calculations indicated a total overall sample prevalence of 1.7% (95% CI 0.9, 2.8). The highest provincial seroprevalences were Xiangkhouang (3.5%, 95% CI 1.6, 6.9) and Xayaboury (2.9% (95% CI 1.3, 5.7). There was no association between antibody response and each of the following factors: location, breed, gender or age. Considering the apparent absence of disease manifestation of PPR in Laos, likely explanations for the antibody positivity could include cross reaction to other Morbilliviruses such as Measles or Canine Distemper, importation of pre‐vaccinated goats, need for test cut‐off re‐evaluation to be region specific, or a subclinical and a less virulent circulating virus. This study highlights that the sampled Lao goat population is highly likely to be naïve to PPRV and therefore at risk of an outbreak, possibly by transboundary incursion of livestock from PPR endemic China. Further work is required in the testing of small ruminants in Laos that may eventually provide evidence for a status of freedom from disease, particularly in support of programs aimed at global PPR eradication.

Особенности иммунного статуса у часто и длительно болеющих детей — жителей Алтайского края

The study of the immune status of often and long-term sick children (OSC) — residents of the Altai Territory, involved 31 male and female children aged 3 to 5 years. All children were followed-up at the children’s clinic at the place of residence as “often sick,” suffering from recurrent respiratory diseases of the upper respiratory tract. The control group consisted of 28 conditionally healthy children aged 3–5 years who were not registered as often sick. All participants underwent a comprehensive clinical and laboratory examination, including a complete blood count, a study of biochemical blood parameters, a comprehensive immunological examination, a comprehensive parasite screening, an examination on herpes virus infections (human papillomavirus, Epstein — Barr virus (EBV), cytomegalovirus (CMV), herpes simplex virus (HSV)). The analysis of microfl ora from the mucosa of the nasal cavity and pharynx revealed both opportunistic and pathogenic microfl ora in the group of OSC. Staphylococcus (S.) epidermidis (in 32% of children), Neisseria spp. (in 23%), S. aureus (in 15%) were most often found. 60% of OSC had a positive antibody (AB) response to EA (IgG) and VCA (IgG) antigens of EBV, as well as positive anti-CMV IgG. The analysis showed that AB to HSV were not detected in isolation from AB to other herpes viruses (EBV, CMV), while AB to CMV were found in 25% of cases, and AB to EBV — in 15%. The remaining 60% of cases accounted for their combination. An immunological examination of children did not reveal pronounced disorders of the immunological status, but there was an apparent decrease in the number of mature T-lymphocytes (CD3+), T-helper cells (CD4+), as well as T-cytotoxic lymphocytes (CD8+). Assessment of interferon (IFN) status revealed a relatively low level of IFN-α in the OSC. Thus, the majority of examined OSC did not have signifi cant disorders of the immune system, which requires local pediatricians to take a more balanced approach to the tactics of their examination. Conflict of interest. The authors declare no conflict of interest.