Serological Response Research Articles

Metabolomic Signatures Differentiate Immune Responses in Avian Influenza Vaccine Recipients.

Avian influenza viruses pose significant risk to human health. Vaccines targeting the hemagglutinin of these viruses are poorly immunogenic without the use of adjuvants. Twenty healthy men and women (18-49 years of age) were randomized to receive 2 doses of inactivated influenza A/H5N1 vaccine alone (IIV) or with AS03 adjuvant (IIV-AS03) 1 month apart. Urine and serum samples were collected on day 0 and on days 1, 3, and 7 following first vaccination and subjected to metabolomics analyses to identify metabolites, metabolic pathways, and metabolite clusters associated with immunization. Seventy-three differentially abundant (DA) serum and 88 urine metabolites were identified for any postvaccination day comparison. Pathway analysis revealed enrichment of tryptophan, tyrosine, and nicotinate metabolism in urine and serum among IIV-AS03 recipients. Increased urine abundance of 4-vinylphenol sulfate on day 1 was associated with serologic response based on hemagglutination inhibition responses. In addition, 9 DA urine metabolites were identified in participants with malaise compared to those without. Our findings suggest that tryptophan, tyrosine, and nicotinate metabolism are upregulated among IIV-AS03 recipients compared with IIV alone. Metabolites within these pathways may serve as measures of immunogenicity and may provide mechanistic insights for adjuvanted vaccines. NCT01573312.

Serological responses and clinical outcomes following a three-dose primary COVID-19 vaccine schedule in kidney transplant recipients and people on dialysis.

Despite vaccination strategies, people with chronic kidney disease, particularly kidney transplant recipients (KTRs), remained at high risk of poor COVID-19 outcomes. We assessed serological responses to the three-dose COVID-19 vaccine schedule in KTRs and people on dialysis, as well as seroresponse predictors and the relationship between responses and breakthrough infection. Plasma from 30 KTRs and 17 people receiving dialysis was tested for anti-Spike receptor binding domain (RBD) IgG and neutralising antibodies (NAb) to the ancestral and Omicron BA.2 variant after Doses 2 and 3 of vaccination. After three doses, KTRs achieved lower anti-Spike RBD IgG levels (P < 0.001) and NAb titres than people receiving dialysis (P = 0.002). Seropositive cross-reactive Omicron neutralisation levels were achieved in 11/27 (40.7%) KTRs and 11/14 (78.6%) dialysis recipients. ChAdOx1/viral-vector vaccine type, higher mycophenolate dose (> 1 g per day) and lower absolute B-cell counts predicted poor serological responses in KTRs. ChAdOx-1 vaccine type and higher monocyte counts were negative predictors in dialysis recipients. Among ancestral NAb seroresponders, higher NAb levels positively correlated with higher Omicron neutralisation (R = 0.9, P < 0.001). More KTRs contracted SARS-CoV-2 infection (14/30; 47%) than dialysis recipients (5/17; 29%) and had more severe disease. Those with breakthrough infections had significantly lower median interdose incremental change in anti-Spike RBD IgG and ancestral NAb titres. Serological responses to COVID-19 vaccines in KTRs lag behind their dialysis counterparts. KTRs remained at high risk of breakthrough infection after their primary vaccination schedule underlining their need for booster doses, strict infection prevention measures and close surveillance.

Evaluation of clinical and serological responses after full-mouth implantation in single-visit versus multiple-session surgery.

This research aimed to evaluate the clinical characteristics of pain and wound healing and serological inflammatory markers after full-mouth implantation in one session compared to several sessions. A single-masked clinical trial was conducted on 20 patients (n=10) receiving full-mouth implants. Patients were randomly divided into two groups. The first group was operated under general anesthesia in one session and the second group in multi-sessions. Inflammation level was evaluated through white blood cell (WBC) and serum C-reactive protein (CRP) before and after surgery by a blood test. Pain and early wound healing (EHS) assessment was conducted after surgery with VAS and EHS indicators, respectively. Serological and clinical parameters were compared by repeated-measures ANOVA and Sidak and Man-Whitney U tests, respectively, using SPSS 20. The CRP level 48 hours postoperatively was not different in the two groups; however, seven days after treatment, it was higher in the multi-session group than in the single-session approach. The WBC was not different between the two groups at evaluated intervals. Serum levels of WBC and CRP increased 48 hours postoperatively and decreased seven days later. EHS showed no difference between the two groups at the three investigated intervals. The amount of VAS 24 and 48 hours and 7 days postoperatively was higher in multi-session surgery than in the one-session approach. In both groups, VAS was not different at 24 and 48 hours postoperatively and decreased over seven days. Full-mouth implant surgery under general anesthesia in one session caused less inflammation and pain postoperatively while presenting the same wound-healing process as the multi-session surgery.

Effects of antineoplastic and immunomodulating agents on postvaccination SARS-CoV-2 breakthrough infections, antibody response, and serological cytokine profile

BackgroundDespite immunization, patients on antineoplastic and immunomodulating agents have a heightened risk of COVID-19 infection. However, accurately attributing this risk to specific medications remains challenging.MethodsAn observational cohort study from December...

Resposta anamnéstica contra o vírus da diarreia viral bovina e herpesvírus bovino tipo 1 em novilhas Holandesas jovens vacinadas com quatro diferentes formulações comerciais

ABSTRACT: This study evaluated the vaccine-induced serological response after administering four commercial formulations containing Bovine Viral Diarrhea Virus (BVDV) type-1, BVDV-2, and Bovine Herpesvirus type 1 (BoHV-1) to young heifers with circulating maternal antibody titers. The study also determined the anamnestic response to vaccinations after the complete metabolization of maternal antibodies when the calves reached six months. Eighty-seven Holstein heifers were selected and randomly distributed into four experimental groups based on the vaccine administered. The four vaccine-based experimental groups were as follows: vaccine A (n = 22), vaccine B (n = 22), vaccine C (n = 24), and vaccine D (n = 19), given on the 60th, 90th, and 180th day of life, respectively. Virus-neutralization (VN) tests were performed at baseline (day 60) and 30 days after administering the second (day 120) and third doses (day 210). We analyzed the effect of vaccine group (P ≤ 0.001), day of vaccination (P ≤ 0.001), and group versus vaccine day interaction (P ≤ 0.001) for antibody titers produced against BVDV-1, BVDV-2, and BoHV-1 using the PROC MIXED method (Statistical Analysis System -SAS 9.4). Antibody titers against BVDV-1, BVDV-2, and BoHV-1 were similar at baseline and on day 60 of life. The mean antibody titers were constant and persisted against BVDV-1 in heifers immunized with vaccines A and C. Heifers immunized with vaccine A alone had a similar effect against BVDV-2. Regarding BoHV-1, the antibody titers decreased between days 60 and 210 in groups B, C, and D. The antibody titer for heifers in group A also decreased between days 60 and day 120, and an intense increase in titers was observed on day 210. After being immunized with formulations B, C, and D, the frequency of animals with titers above protective levels for BVDV-1, BVDV-2, and BoHV-1 was very low or null. Indicators of anamnestic response were observed in heifers vaccinated with formulation A only. Therefore, it can be concluded that passive immunity negatively interferes with antibody production after vaccination.

A machine learning approach to identify groups of patients with hematological malignant disorders

Background and ObjectiveVaccination against SARS-CoV-2 in immunocompromised patients with hematologic malignancies (HM) is crucial to reduce the severity of COVID-19. Despite vaccination efforts, over a third of HM patients remain unresponsive, increasing their risk of severe breakthrough infections. This study aims to leverage machine learning's adaptability to COVID-19 dynamics, efficiently selecting patient-specific features to enhance predictions and improve healthcare strategies. Highlighting the complex COVID-hematology connection, the focus is on interpretable machine learning to provide valuable insights to clinicians and biologists. MethodsThe study evaluated a dataset with 1166 patients with hematological diseases. The output was the achievement or non-achievement of a serological response after full COVID-19 vaccination. Various machine learning methods were applied, with the best model selected based on metrics such as the Area Under the Curve (AUC), Sensitivity, Specificity, and Matthew Correlation Coefficient (MCC). Individual SHAP values were obtained for the best model, and Principal Component Analysis (PCA) was applied to these values. The patient profiles were then analyzed within identified clusters. ResultsSupport vector machine (SVM) emerged as the best-performing model. PCA applied to SVM-derived SHAP values resulted in four perfectly separated clusters. These clusters are characterized by the proportion of patients that generate antibodies (PPGA). Cluster 1, with the second-highest PPGA (69.91%), included patients with aggressive diseases and factors contributing to increased immunodeficiency. Cluster 2 had the lowest PPGA (33.3%), but the small sample size limited conclusive findings. Cluster 3, representing the majority of the population, exhibited a high rate of antibody generation (84.39%) and a better prognosis compared to cluster 1. Cluster 4, with a PPGA of 66.33%, included patients with B-cell non-Hodgkin's lymphoma on corticosteroid therapy. ConclusionsThe methodology successfully identified four separate patient clusters using Machine Learning and Explainable AI (XAI). We then analyzed each cluster based on the percentage of HM patients who generated antibodies after COVID-19 vaccination. The study suggests the methodology's potential applicability to other diseases, highlighting the importance of interpretable ML in healthcare research and decision-making.

Humoral Response Following 3 Doses of mRNA COVID-19 Vaccines in Patients With Non-Dialysis-Dependent CKD: An Observational Study.

Chronic kidney disease (CKD) is associated with a lower serologic response to vaccination compared to the general population. There is limited information regarding the serologic response to coronavirus disease 2019 (COVID-19) vaccination in the non-dialysis-dependent CKD (NDD-CKD) population, particularly after the third dose and whether this response varies by estimated glomerular filtration rate (eGFR). The NDD-CKD (G1-G5) patients who received 3 doses of mRNA COVID-19 vaccines were recruited from renal clinics within British Columbia and Ontario, Canada. Between August 27, 2021, and November 30, 2022, blood samples were collected serially for serological testing every 3 months within a 9-month follow-up period. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-spike, anti-receptor binding domain (RBD), and anti-nucleocapsid protein (NP) levels were determined by enzyme-linked immunosorbent assay (ELISA). Among 285 NDD-CKD patients, the median age was 67 (interquartile range [IQR], 52-77) years, 58% were men, 48% received BNT162b2 as their third dose, 22% were on immunosuppressive treatment, and COVID-19 infection by anti-NP seropositivity was observed in 37 of 285 (13%) patients. Following the third dose, anti-spike and anti-RBD levels peaked at 2 months, with geometric mean levels at 1131 and 1672 binding antibody units per milliliter (BAU/mL), respectively, and seropositivity rates above 93% and 85%, respectively, over the 9-month follow-up period. There was no association between eGFR or urine albumin-creatinine ratio (ACR) with mounting a robust antibody response or in antibody levels over time. The NDD-CKD patients on immunosuppressive treatment were less likely to mount a robust anti-spike response in univariable (odds ratio [OR] 0.43, 95% confidence interval [CI]: 0.20, 0.93) and multivariable (OR 0.52, 95% CI: 0.25, 1.10) analyses. An interaction between age, immunoglobulin G (IgG) antibody levels, and time was observed in both unadjusted (anti-spike: P = .005; anti-RBD: P = .03) and adjusted (anti-spike: P = .004; anti-RBD: P = .03) models, with older individuals having a more pronounced decline in antibody levels over time. Most NDD-CKD patients were seropositive for anti-spike and anti-RBD after 3 doses of mRNA COVID-19 vaccines and we did not observe any differences in the antibody response by eGFR.

Single ChAdOx1 nCoV-19 dose elicits stronger immune response in previously infected individuals than in SARS-CoV2 naive persons.

Current vaccines against COVID-19 effectively reduce morbidity and mortality and are vitally important for controlling the pandemic. Between December 2020 and February 2021, adenoviral vector vaccines such as ChAdOx1 (AstraZeneca-Oxford) were put in use. Recent reports demonstrate robust serological responses to a single dose of messenger RNA vaccines in individuals previously infected with SARS-CoV-2. We aimed to study the association between previous COVID-19 infection and antibody levels after a single dose of ChAdOx1 nCoV-19. This cross-sectional study was conducted on 657 individuals who were either convalescent or SARS-CoV-2 naive and had received one dose of ChAdOx1 (AstraZeneca). A questionnaire was used to collect data on age, sex, and self-reported history of COVID-19 infection. We then compared the average levels of immunoglobulin G (IgG) between the previously infected and COVID-19-naive participants. We compared the antibody responses of individuals with confirmed prior COVID-19 infection with those of individuals without prior evidence of infection. The mean antibody levels in those who reported no history of COVID-19 infection were substantially lower than in those who were previously infected, in both males and females. Sex-related differences were observed when we compared antibody levels between men and women. In males, anti-S IgG antibody levels were higher in those who had been previously infected (156.1 vs. 87.69 AU/mL, p = .009), compared with the same pattern was observed in females (113.5 vs. 90.69 AU/mL, p = .005). Previous COVID-19 infection is associated with higher levels of SARS-CoV-2 antibodies following ChAdOx1 (AstraZeneca) vaccination. Our finding supports the notion that a single dose of ChAdOx1 nCoV-19 administered post-SARS-CoV-2 infection serves as an effective immune booster. This provides a possible rationale for a single-dose vaccine regimen for previously infected individuals.

A Study on Antibody Response among COVID-19 Noninfected Population – Need for Hour

Abstract Introduction: In the year 2020, COVID-19 emerged as a pandemic resulting in millions of deaths worldwide and negatively impacted the health, infrastructure, and economy of the globe. The disease was believed to be acquired from animals (Bats), however, man-to-man transmission happened through aerosols o/or and direct contact. Seroprevalence studies in different countries among various populations were conducted to understand the immune responses against the virus; also, to estimate the proximity in reaching herd immunity. Aim: The aim of this study was to study antibody response among the COVID-19 noninfected population. Materials and Methods: A prospective cross-sectional study was done during the months of January–February 2023. The study was conducted in the Viral Research and Diagnostic Laboratory, Department of Microbiology, Osmania Medical College. Nursing and Diploma in Medical Laboratory Technology (DMLT) students who did not test positive for COVID-19 reverse transcription–polymerase chain reaction during and after the pandemic were included in the study. Blood samples were tested for COVID-19 immunoglobulin (Ig) G antibodies using commercial enzyme-linked immunosorbent assay kit. A comparison among vaccinated and nonvaccinated groups was performed. Results: A total of 90 blood samples were tested, of which 45 belonged to the vaccinated group and the other 45 were of the nonvaccinated group. Among the vaccinated group, total of 45 samples tested positive for COVID-19 IgG antibodies (100%). Whereas 38 (84.4%) among the nonvaccinated group showed positive COVID-19 IgG antibodies; while 7 (15.6%) samples of nonvaccinated group tested negative for antibodies. A total of 83 out of 90 (92.2%) showed evidence of COVID-19 IgG antibodies. Conclusion: Despite the controlled COVID-19 pandemic situation, the novel disease has posed serious challenges to the medical field. Although the population in this study showed good serological response, herd immunity to COVID-19 can be achieved if more than 80% of the entire population becomes immune. In this study, 84.4% of the population showed positive for COVID-19 IgG antibodies hinting toward achieving herd immunity. However, regular vaccination and sero-surveillance studies are needed for sustaining community protection.

Characterizing the acute antibody response of monkeypox and MVA-BN vaccine following an Australian outbreak.

In response to the emergence of the monkeypox virus (MPXV) in Australia in May 2022, we developed and evaluated indirect immunofluorescence assays (IFA) for MPXV and Vaccinia virus (VACV) IgG and IgM antibodies using serum samples from patients with nucleic acid amplification test (NAAT)-confirmed mpox and uninfected unvaccinated controls. Additionally, 47 healthcare workers receiving two doses of the third-generation smallpox vaccine Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) undertook serial serum collection to describe the serological response to vaccination. MPXV antibodies were detected in 16/18 individuals with NAAT-confirmedmpox (sensitivity 0.89, specificity 1.00), and VACV antibodies were detected in 28/29 individuals who received two doses of MVA-BN vaccine (sensitivity 0.97, specificity 1.00). Detectable antibody in subjects historically vaccinated with early-generation vaccines against smallpox was found in 7/7 subjects, at a median of 48 years following vaccination. MPXVNAAT-positivepatients with serum samples collected within the first 14 days after rash onset had detectable IgG and IgM in 9/12 and 5/12 of patients, respectively, with maintenance of IgG and disappearance of IgM titersafter 60 days. Whilespecificity was high when testing unvaccinated and uninfected subjects, significant cross-reactivity between MPXV and VACV antibodies was observed.

The use of recombinant K39, KMP11, and crude antigen-based indirect ELISA as a serological diagnostic tool and a measure of exposure for cutaneous leishmaniasis in Sri Lanka.

Cutaneous leishmaniasis (CL) in Sri Lanka is caused by Leishmania donovani, a parasite widely known to cause visceral leishmaniasis. Despite the fact that CL is not generally believed to elicit serological immune responses, recent studies show the presence of antibody responses against this atypical form of CL. This study assesses the potential of using recombinant K39 (rK39), KMP11, and crude parasite antigen-based indirect ELISAs as serological diagnostic tools and measures of exposure for CL in Sri Lanka. The study used serum samples from confirmed CL patients (n = 266) and apparently healthy individuals from endemic settings (n = 411). Serum samples from individuals residing in non-endemic areas were used as negative controls. In-house indirect ELISAs were optimized and validated for recombinant antigens. Previously validated crude parasite extract-based indirect ELISA was performed for comparison. The statistical analyses were performed using SPSS v26.0. The rK39 (sensitivity = 71.2%, specificity = 64%) and KMP11 (sensitivity = 79.2%, specificity = 71.4%) based indirect ELISA were shown to be less suitable for the diagnosis of CL, while crude parasite extract-based indirect ELISA (sensitivity = 82.4%, specificity = 85.7%) might be a better method of diagnosis. All 03 ELISAs seemed to be good methods as measures of exposure since correlations were observed between the seropositivity of all 03 ELISAs (rK39: p = 0.037, KMP11: p = 0.007, CrudeAg: p = 0.000) with provincial case incidences. The findings will be important in identifying the disease hotspots in order to design the control measures for CL induced by L. donovani in Sri Lanka.

Сучасні підходи до вакцинації в дітей з різними варіантами первинних та вторинних імунодефіцитів (огляд літератури)

Chronic disease and immunosuppression increase the risk of vaccine-preventable infections, complications, and mortality from infectious diseases. Safe vaccination and achieving an adequate serological response to vaccination are crucial aspects of the management of such patients. Purpose - to analyze data from domestic and foreign medical literature regarding modern approaches to vaccination of children with various primary and secondary immunodeficiency diseases. The majority of children with primary immunodeficiency who have preserved antibody production can demonstrate an immune response to vaccination, but this response can be rapidly lost over time. Limitations to vaccinating children with primary immunodeficiency are related to the use of live vaccines in conditions where the cellular immune system is compromised. Patients with primary antibody deficiency are treated with immunoglobulin preparations and depend on the presence of specific antibodies at a protective level against infectious pathogens, including vaccine-preventable infections. Several studies have shown the effectiveness of intravenous immunoglobulin treatment in reducing the number and severity of infections in patients with humoral deficiency. The majority of children with rheumatic diseases vaccinated according to the Schedule of Routine Immunisations before starting immunosuppressive therapy have protective antibody levels against vaccine-preventable infections. All non-live vaccines can be administered without restrictions, but should be administered two weeks before immunosuppressive therapy to increase immunogenicity. Children receiving high doses of immunosuppressive therapy should avoid receiving live attenuated vaccines. No conflict of interests was declared by the author.

SARS-CoV-2 Antibody Responses in Newly Recovered Patients from Covid-19 Infection

Background: The coronavirus disease 2019 pandemic continues, causing considerable morbidity and mortality worldwide. Real-time reverse transcription polymerase chain reaction (RT-PCR) diagnostic assays are a goal standard for case ascertainment and diagnosis. Comparing to PCR, serological testing is advantageous with faster turn-around time, high-throughput and less workload. However, the clinical value of antibodies largely depends on the understanding of host antibody responses during infection. Objective: To investigate the dynamics of (Immunoglobulin M (IgM) and Immunoglobulin G (IgG)) in response to SARS-CoV-2 in patients newly recovered from different severity Covid-19 infection in Baquba-Iraq. Patients and Methods: In this cross sectional study a (93) patients with recent covid-19 infection who came to the central blood bank of Diyala for convalescent plasma donation for the period from the 1st June 2020 till 1st August 2020 were enrolled. The questionnaire form were filled regarding the time of infection, clinical manifestations, severity and polymerase chain reaction (PCR) results. While blood were taken for antibody titer measurement using the SARS-CoV-2 IgM and IgG VIDAS test. Results: Male constitute about 91% of the study population. About 74% of the cases were below 40 years old. Fifty four of the patients had mild disease, 28% had moderate severity while the other 18% had severe type of the disease. fatigue and fever were the most common symptoms and seen in 87%,84% respectively. IgM Antibodies start to be positive before 21 days post infection mainly in mild and moderate cases 100%, While 0% of severe cases were positive at this time. After 49 day from the time of the infection 67%and 75% of the mild and moderate cases where IgM positive respectively and 100% of the severe cases where IgM positive. IgG Antibodies were positive in 100%, 0% of the mild and severe cases respectively at 21 day post infection but it's positive in 100% of both mild and severe cases after 49 day post infection. Conclusion: Although the serological response for SARS-CoV-2 appears in the first three weeks from the disease onset this response differs from patient to another according to the time from the infection and the severity of the infection. Keywords: SARS-CoV-2, serological response, Immunoglobulin G Antibodies.

SARS-CoV-2 Antibody Responses in Newly Recovered Patients from Covid-19 Infection

Background: The coronavirus disease 2019 pandemic continues, causing considerable morbidity and mortality worldwide. Real-time reverse transcription polymerase chain reaction (RT-PCR) diagnostic assays are a goal standard for case ascertainment and diagnosis. Comparing to PCR, serological testing is advantageous with faster turn-around time, high-throughput and less workload. However, the clinical value of antibodies largely depends on the understanding of host antibody responses during infection. Immunoglobulin G (IgG)) in response to SARS-CoV-2 in patients newly recovered from different severity Covid-19 infection in Baquba-Iraq. Patients and Methods: In this cross sectional study a (93) patients with recent covid-19 infection who came to the central blood bank of Diyala for convalescent plasma donation for the period from the 1st June 2020 till 1st August 2020 were enrolled. The questionnaire form were filled regarding the time of infection, clinical manifestations, severity and polymerase chain reaction (PCR) results. While blood were taken for antibody titer measurement using the SARS-CoV-2 IgM and IgG VIDAS test. Results: Male constitute about 91% of the study population. About 74% of the cases were below 40 years old. Fifty four of the patients had mild disease, 28% had moderate severity while the other 18% had severe type of the disease. fatigue and fever were the most common symptoms and seen in 87%,84% respectively. IgM Antibodies start to be positive before 21 days post infection mainly in mild and moderate cases 100%, While 0% of severe cases were positive at this time. After 49 day from the time of the infection 67%and 75% of the mild and moderate cases where IgM positive respectively and 100% of the severe cases where IgM positive. IgG Antibodies were positive in 100%, 0% of the mild and severe cases respectively at 21 day post infection but it's positive in 100% of both mild and severe cases after 49 day post infection. Conclusion: : Although the serological response for SARS-CoV-2 appears in the first three weeks from the disease onset this response differs from patient to another according to the time from the infection and the severity of the infection.

In vivo challenge studies on vaccinated chickens indicate a virus genotype mismatched vaccine still offers significant protection against NDV

Although commercial vaccines against Newcastle Disease have been available for decades, outbreaks still occur in the face of vaccination Further vaccination may accelerate viral evolution resulting in a further reduction in vaccine efficacy. A key question is whether genotype-matched vaccines can confer better protection against contemporary type 1 Avian Paramyxoviruses. To assess this, an in vivo vaccine-challenge study was undertaken to assess protection afforded by ‘genotype-matched’ and commercial vaccine formulations. Groups of chickens were vaccinated twice (prime-boost) with an inactivated preparation of either La Sota Clone 30, AV632-chicken-Cyprus-13 (genotype VII.2), or mock vaccine, and later challenged with virulent AV632-chicken-Cyprus-13. Post vaccinal serological responses differed, although both vaccination/challenge groups showed similar levels of clinical protection compared to the unvaccinated group, where 100 % mortality was observed. Shedding was significantly reduced in the vaccinated groups compared to the unvaccinated group. Virus dissemination in the tissues of vaccinated birds was comparable, but onset of infection was delayed. Two mutations were observed in the HN gene of the heterologous vaccine group; H199N and I192M, the latter thought to be associated with increased fusogenic potential. These data demonstrate that existing vaccine formulations confer similar levels of clinical protection to contemporary strains and that the antigenic heterogeneity of circulating strains does not impact upon shedding profiles in immunised birds. In conclusion, the ability of virulent APMV-1 to cause disease in vaccinated flocks is unlikely to be the result of antigenic mismatch alone, and other factors likely contribute to vaccination failure and breakthrough.

Impact of the Route and Schedule of Immunization on the Serological and Virological Response of Chronic Hepatitis B Patients Treated with HeberNasvac.

Freyre FM, Aguiar JA, Cinza Z, et al. Impact of the Route and Schedule of Immunization on the Serological and Virological Response of Chronic Hepatitis B Patients Treated with HeberNasvac. Euroasian J Hepato-Gastroenterol 2023;13(2):73-78.

Antibody response and risk of reinfection over 2 years among the patients with first wave of COVID-19

ObjectivesTo describe the dynamics and factors related to natural and hybrid humoral response against the SARS-CoV-2 and risk of reinfection among first-wave patients. MethodsA prospective longitudinal study with periodic serological follow-up after acute onset of all recovered patients with SARS-CoV-2 infection cared in Udine Hospital (March–May 2020). Nucleocapsid (N) protein and spike receptor-binding domain (S-RBD) antibody tests were used to distinguish natural and vaccine-induced response. ResultsOverall, 153 patients (66 men, mean age 56 years) were followed for a median of 27.3 (interquartile range 26.9–27.8) months. Seroreversion was 98.5% (95% CI: 96.8–99.4) for SARS-CoV-2-N IgM at 1 year and 57.4% (95% CI: 51.5–63.5) for SARS-CoV-2-N IgG at 2 years. Initial serological response (hazard ratio [HR]: 0.99, 95% CI: 0.99–0.99, p 0.002 for IgM and HR: 0.97, 95% CI: 0.97–0.98, p < 0.001 for IgG) and severity of acute infection (HR: 0.62, 95% CI: 0.39–0.96, p 0.033 for IgM and HR: 0.60, 95% CI: 0.37–0.99, p < 0.001 for IgG) were independently associated with persistent SARS-CoV-2-N IgM/IgG response. Older age and smoker status were associated with long-term SARS-CoV-2-N IgM and SARS-CoV-2-N IgG, respectively (HR: 0.75, 95% CI: 0.57–0.98, p 0.038; HR: 1.77, 95% CI: 1.19–2.61, p 0.004 respectively). All patients maintained SARS-CoV-2-S-RBD IgG response at 24-month follow-up. Reinfections occurred in 25 of 153 (16.3%) patients, mostly during the omicron circulation. Reinfection rates did not differ significantly between SARS-CoV-2-N IgG seronegative and seropositive patients (14/89, 15.7% vs. 10/62, 16.1%, p 0.947). Unvaccinated patients had higher risk of reinfection (4/7, 57.1% vs. vaccinated 21/146, 14.4%, p 0.014). DiscussionFirst-wave patients had durable natural humoral immunity in 40% and anti-S-RBD response in 100% up to 2 years after infection. Natural humoral response alone was not protective against reinfections with omicron SARS-CoV-2 variants, whereas vaccination was effective to reduce the risk of a new infection.

Immunogenicity and durability against Omicron BA.1, BA.2 and BA.4/5 variants at 3–4 months after a heterologous COVID-19 booster vaccine in healthy adults with a two-doses CoronaVac vaccination

BackgroundSeveral countries have authorized a booster vaccine campaign to combat the spread of COVID-19. Data on persistence of booster vaccine‐induced immunity against new Omicron subvariants are still limited. Therefore, our study aimed to determine the serological immune response of COVID-19 booster after CoronaVac-priming. MethodsA total of 187 CoronaVac-primed participants were enrolled and received an inactivated (BBIBP), viral vector (AZD1222) or mRNA vaccine (full-/half-dose BNT162B2, full-/half-dose mRNA-1273) as a booster dose. The persistence of humoral immunity both binding and neutralizing antibodies against wild-type and Omicron was determined on day 90–120 after booster. ResultsA waning of total RBD immunoglobulin (Ig) levels, anti-RBD IgG, and neutralizing antibodies against Omicron BA.1, BA.2, and BA.4/5 variants was observed 90–120 days after booster vaccination. Participants who received mRNA-1273 had the highest persistence of the immunogenicity response, followed by BNT162b2, AZD1222, and BBIBP-CorV. The responses between full and half doses of mRNA-1273 were comparable. The percentage reduction of binding antibody ranged from 50 % to 75 % among all booster vaccine. ConclusionsThe antibody response substantially waned after 90–120 days post-booster dose. The heterologous mRNA and the viral vector booster demonstrated higher detectable rate of humoral immune responses against the Omicron variant compared to the inactivated BBIBP booster. Nevertheless, an additional fourth dose is recommended to maintain immune response against infection.

Humoral Immune Responses after an Omicron-Adapted Booster BNT162b2 Vaccination in Patients with Lymphoid Malignancies.

To accommodate waning COVID-19 vaccine immunity to emerging SARS-CoV-2 variants, variant-adapted mRNA vaccines have been introduced. Here, we examine serological responses to the BA.1 and BA.4-5 Omicron variant-adapted BNT162b2 COVID-19 vaccines in people with lymphoid malignancies. We included 233 patients with lymphoid malignancies (chronic lymphocytic B-cell leukemia: 73 (31.3%), lymphoma: 89 (38.2%), multiple myeloma/amyloidosis: 71 (30.5%)), who received an Omicron-adapted mRNA-based COVID-19 vaccine. IgG and neutralizing antibodies specific for the receptor-binding domain (RBD) of SARS-CoV-2 were measured using ELISA-based methods. Differences in antibody concentrations and neutralizing capacity and associations with risk factors were assessed using mixed-effects models. Over the period of vaccination with an Omicron-adapted COVID-19 vaccine, the predicted mean concentration of anti-RBD IgG increased by 0.09 log10 AU/mL/month (95% CI: 0.07; 0.11) in patients with lymphoid malignancies across diagnoses. The predicted mean neutralizing capacity increased by 0.9 percent points/month (95% CI: 0.2; 1.6). We found no associations between the increase in antibody concentration or neutralizing capacity and the variant included in the adapted vaccine. In conclusion, a discrete increase in antibody concentrations and neutralizing capacity was found over the course of Omicron-adapted vaccination in patients with lymphoid malignancies regardless of the adapted vaccine variant, indicating a beneficial effect of Omicron-adapted booster vaccination in this population.

Employment of a high throughput functional assay to define the critical factors that influence vaccine induced cross-variant neutralizing antibodies for SARS-CoV-2

The scale and duration of neutralizing antibody responses targeting SARS-CoV-2 viral variants represents a critically important serological parameter that predicts protective immunity for COVID-19. In this study, we describe the development and employment of a new functional assay that measures neutralizing antibodies for SARS-CoV-2 and present longitudinal data illustrating the impact of age, sex and comorbidities on the kinetics and strength of vaccine-induced antibody responses for key variants in an Asian volunteer cohort. We also present an accurate quantitation of serological responses for SARS-CoV-2 that exploits a unique set of in-house, recombinant human monoclonal antibodies targeting the viral Spike and nucleocapsid proteins and demonstrate a reduction in neutralizing antibody titres across all groups 6 months post-vaccination. We also observe a marked reduction in the serological binding activity and neutralizing responses targeting recently newly emerged Omicron variants including XBB 1.5 and highlight a significant increase in cross-protective neutralizing antibody responses following a third dose (boost) of vaccine. These data illustrate how key virological factors such as immune escape mutations combined with host demographic factors such as age and sex of the vaccinated individual influence the strength and duration of cross-protective serological immunity for COVID-19.