Low Antibody Research Articles

Predictors of Therapy Success in Weekly Adalimumab for Refractory Uveitis: A Retrospective Cohort Study

PurposeTo determine predictors of treatment success after dose escalation of adalimumab, including measurement of anti-adalimumab antibodies as a predictor of success DesignRetrospective clinical cohort study SettingSingle-center academic institution Study PopulationPatients with noninfectious uveitis who were inadequately controlled or developed recurrent disease on biweekly adalimumab and required dose escalation or therapy modification Observation ProceduresPatients who had anti-adalimumab antibodies checked with resultant low to intermediate levels were compared to patients who had no testing performed prior to adalimumab dose escalation. Of note, patients with testing and resultant high levels of anti-adalimumab antibodies were not escalated. Predictors of escalation success and utility of antibody testing prior to escalation were analyzed using Kaplan Meier survival analysis and Cox proportional hazard models. Main Outcome MeasuresTreatment success defined as anterior chamber grade ≤0.5+ cell, topical corticosteroids ≤1 drop/day, oral prednisone ≤5 mg/day, resolution of macular edema, and resolution of angiographic signs of inflammation without any addition or escalation of therapy. Results24 patients had antibodies tested with low to intermediate levels (average: 32.3 ng/mL, range: 0 – 154), while 41 did not have antibody testing. A greater treatment success rate post escalation was observed among the “low antibody” group compared to the “no testing” group (HR: 2.63, standard error: 1.19, p=0.031, 95% CI 1.09 – 6.37). Among the entire cohort, patients with panuveitis (n = 14) had a lower treatment success rate compared to the reference of anterior uveitis (n = 26) (HR: 0.09, standard error: 0.11, p = 0.05, 95% CI 0.01 – 0.99). ConclusionsPatients with low anti-adalimumab antibodies had a greater treatment success compared to patients in whom antibodies were not checked. This suggests a utility to checking antibodies prior to dose escalation and that low levels of antibodies may confer a success advantage. Overall, patients with panuveitis had a lower rate of success after escalation while patients with anterior uveitis patients had a very high rate of success suggesting that certain disease characteristics may guide clinicians when determining who to escalate versus changing therapy.

Knockdown of swine leukocyte antigen expression in porcine lung transplants enables graft survival without immunosuppression.

Immune rejection remains the major obstacle to long-term survival of allogeneic lung transplants. The expression of major histocompatibility complex molecules and minor histocompatibility antigens triggers allogeneic immune responses that can lead to allograft rejection. Transplant outcomes therefore depend on long-term immunosuppression, which is associated with severe side effects. To address this problem, we investigated the effect of genetically engineered transplants with permanently down-regulated swine leukocyte antigen (SLA) expression to prevent rejection in a porcine allogeneic lung transplantation (LTx) model. Minipig donor lungs with unmodified SLA expression (control group, n = 7) or with modified SLA expression (treatment group, n = 7) were used to evaluate the effects of SLA knockdown on allograft survival and on the nature and strength of immune responses after terminating an initial 4-week period of immunosuppression after LTx. Genetic engineering to down-regulate SLA expression was achieved during ex vivo lung perfusion by lentiviral transduction of short hairpin RNAs targeting mRNAs encoding β2-microglobulin and class II transactivator. Whereas all grafts in the control group were rejected within 3 months, five of seven animals in the treatment group maintained graft survival without immunosuppression during the 2-year monitoring period. Compared with controls, SLA-silenced lung recipients had lower donor-specific antibodies and proinflammatory cytokine concentrations in the serum. Together, these data demonstrate a survival benefit of SLA-down-regulated lung transplants in the absence of immunosuppression.

HSV-1 and Cellular miRNAs in CSF-Derived Exosomes as Diagnostically Relevant Biomarkers for Neuroinflammation.

Virus-associated chronic inflammation may contribute to autoimmunity in a number of diseases. In the brain, autoimmune encephalitis appears related to fluctuating reactivation states of neurotropic viruses. In addition, viral miRNAs and proteins can be transmitted via exosomes, which constitute novel but highly relevant mediators of cellular communication. The current study questioned the role of HSV-1-encoded and host-derived miRNAs in cerebrospinal fluid (CSF)-derived exosomes, enriched from stress-induced neuroinflammatory diseases, mainly subarachnoid hemorrhage (SAH), psychiatric disorders (AF and SZ), and various other neuroinflammatory diseases. The results were compared with CSF exosomes from control donors devoid of any neuroinflammatory pathology. Serology proved positive, but variable immunity against herpesviruses in the majority of patients, except controls. Selective ultrastructural examinations identified distinct, herpesvirus-like particles in CSF-derived lymphocytes and monocytes. The likely release of extracellular vesicles and exosomes was most frequently observed from CSF monocytes. The exosomes released were structurally similar to highly purified stem-cell-derived exosomes. Exosomal RNA was quantified for HSV-1-derived miR-H2-3p, miR-H3-3p, miR-H4-3p, miR-H4-5p, miR-H6-3p, miR-H27 and host-derived miR-21-5p, miR-146a-5p, miR-155-5p, and miR-138-5p and correlated with the oxidative stress chemokine IL-8 and the axonal damage marker neurofilament light chain (NfL). Replication-associated miR-H27 correlated with neuronal damage marker NfL, and cell-derived miR-155-5p correlated with oxidative stress marker IL-8. Elevated miR-138-5p targeting HSV-1 latency-associated ICP0 inversely correlated with lower HSV-1 antibodies in CSF. In summary, miR-H27 and miR-155-5p may constitute neuroinflammatory markers for delineating frequent and fluctuating HSV-1 replication and NfL-related axonal damage in addition to the oxidative stress cytokine IL-8 in the brain. Tentatively, HSV-1 remains a relevant pathogen conditioning autoimmune processes and a psychiatric clinical phenotype.

Sustained chronic inflammation and altered childhood vaccine responses in children exposed to Zika virus

Congenital Zika virus (ZIKV) infection leads to severe newborn abnormalities, but its long-term impact on childhood immunity is not well understood. This study aims to investigate the serum proteomics in children exposed to ZIKV during pregnancy to understand potential immunological consequences during early childhood. The study included ZIKV-exposed infants (ZEI) at birth (n=42) and children exposed to ZIKV (ZEC) at two years of age (n=20) exposed to ZIKV during pregnancy, as well as healthy controls. Serum proteomic analysis was performed on these groups to assess inflammation and immune profiles. Additionally, antibody titres against two common childhood vaccines, DTaP and MMR, were measured in healthy controls (n=50) and ZEC (n=92) to evaluate vaccine-induced immunity. Results showed elevated inflammation in ZEI with birth abnormalities. Among ZEC, despite most having normal clinical outcomes at two years, their serum proteomics indicated a bias towards Th1-mediated immune responses. Notably, ZEC displayed reduced anti-Diphtheria toxin and anti-Clostridium tetani IgG levels against DTaP and MMR vaccines. They also exhibited lower antibody titres particularly against Th2-biased DTaP vaccines, but not Th1-biased MMR vaccines. In conclusion, the study highlights the long-term immunological consequences of congenital ZIKV exposure. Heightened inflammation was observed in ZEI with abnormalities at birth, while ZEC maintained a chronic Th1-biased immune profile. The impaired response to Th2-biased vaccines raises concerns about lasting effects of ZIKV exposure on immune responses. Consequently, there is a need for continued longitudinal clinical monitoring to identify potential immune-related complications arising from prenatal exposure to ZIKV. This work was partially funded by the National Institute of Allergy and Infectious Diseases (NIAID) and National Institute of Dental and Craniofacial Research (NIDCR).

Assessment of Antibody Titers after 6 Months of Vaccination against SARS-COV-2 in Patients with CKD Stage 4, 5 and CKD 5d

Background: Since the pandemic of COVID-19 started from December 2019, remarkable numbers of infections and deaths associated with COVID-19 have been recorded worldwide. Chronic kidney disease patients are particularly at high risk of infections due to impairments in the innate and adaptive immune systems. Adequate humoral (antibody) and cellular (T cell-driven) immunity are required to minimize pathogen entry and promote pathogen clearance to enable infection control. Vaccination can generate cellular and humoral immunity against this specific pathogen. COVID-19 prevention through successful vaccination is therefore paramount in chronic kidney disease population. But vaccination efficacy is diminished in these patients because premature ageing of the immune system and chronic systemic low- grade inflammation are the main causes of immune alteration in these patients. Therefore, it is urgently necessary to establish a different vaccination strategy for chronic kidney disease and dialysis patient in terms of the dose and administration time. Aims: This study aimed to assessment of antibody titers after vaccination against SARS-COV-2 in patients with chronic kidney disease stage 4, 5 on conservative management and maintenance haemodialysis. Methods: This prospective observational comparative was conducted in Nephrology department of Dhaka Medical College Hospital. Selectionof patients was done by purposive sampling according to inclusion and exclusion criteria. Total 135 patients distributed in three groups: 45 patients of chronic kidney disease (CKD) stage 4, 5 on conservative management, 45 patients on maintenance haemodialysis (MHD) and 45 healthy controls were approached for the study who were receiving SARS-COV-2 vaccination. Demographic, clinical and laboratory data were collected initially. At first a pre vaccination sample or 1st sample was taken for antibody measurement. Then participants from all groups were given 2 doses MODERNA vaccine containing 100 µg in 0.5 ml each in 28 days apart. Then after 14 days of 1st dose of vaccination the 2nd samples were taken, 3rd samples were taken 14 days after the 2nd dose vaccination. Study populations were subdivided into two groups according to pre vaccination SARS-COV-2 antibody titer; seropositive- positive response before vaccination and seronegative- negative response before vaccination. They were also divided into two groups according to quantitive antibody response; positive response- values ≥10 DU/mL were positive Negative response- values of <10 DU/mL were negative. Result: Seroconversion rate was around 20% among study participants before vaccination. 14 days after the 1st dose of vaccination, 90.04% patients had positive immune response in CKD stage 4, 5 on conservative management group whereas in MHD group 84.82% responded to vaccination and immune response in control group was 100%. Immune response is 100% among all the groups after 14 days of 2nd dose of vaccination but the concentration of antibody differs significantly among the study groups. Responders were comparatively younger with normal BMI. Conclusion: Haemodialysis patients as well as patients with chronic kidney disease stage 4, 5 on conservative management showed a favorable but profoundly lower early antibody response, which decreased substantially during follow-up.

Immunogenicity of the Inactivated SARS-CoV-2 Vaccine (BBIBPCorV) in Hemodialysis Patients: A Case-Control Study

Background: Studies have shown that immune responses to COVID-19 vaccines are impaired in dialysis patients, which may affect their immunity to vaccines. Therefore, this study aimed to evaluate SARS-COV-2 neutralizing antibodies in hemodialysis patients for 2 and 6 weeks after receiving inactivated Sinopharm vaccine. Method: In this study, 172 people were divided into two groups. The first group included 108 hemodialysis patients, while the second group included 64 health workers as a control group. To evaluate SARS-COV-2 neutralizing antibody titers, peripheral blood samples were collected from all participants 2 and 6 weeks after receiving the second dose of the Sinopharm vaccine. Samples were centrifuged, and the neutralizing antibody against the receptor-binding domain (RBD) was determined using the indirect ELISA technique. Results: Hemodialysis patients had lower IgG-neutralizing antibody titers than the control group (P <0.001). The titers of SARS-COV-2 neutralizing antibodies were not significantly different at two weeks compared to six weeks after vaccination (P=0.9204). Our findings showed a significant increase in titers of IgGneutralizing antibodies after vaccination in people with a history of COVID-19 (P=0.002). The seropositivity rate for neutralizing antibodies against RBD was significantly different between seropositive (immune) and seronegative (non-immune) patients six weeks after vaccination (P=0.022). Conclusion: The titers of neutralizing antibodies against SARS-COV-2 were lower in hemodialysis patients than in healthy individuals. This is probably due to the poor immune system. However, patients who received two doses of inactivated Sinopharm vaccine showed a higher antibody titer six weeks after vaccination.

Significant Long-Term Prevention of High Sensitization After Kidney Allograft Failure by Maintaining Calcineurin Inhibitor-Based Immunosuppression.

Broad national or international programs contribute to mitigating the expected longer waiting list (WL) time for sensitized patients but with minor benefits for highly sensitized subjects. Therefore, strategies to prevent high sensitization are urgently required. In this study, we investigated the risk of developing highly sensitized patients with different immunosuppressive (IS) handling after kidney allograft failure (KAF). Data from 185 patients with KAF, retransplanted/relisted from 2010 to 2020 in two regions of Italy that share the same regional WL, were analyzed. Patients were categorized according to IS management at 12 months after KAF as follows: patients maintaining IS with calcineurin inhibitors (CNI) (late withdrawal group [LWG], n = 58) and those who withdrew all IS therapy or were on steroids only (early withdrawal group [EWG], n = 127). Patients in the LWG showed lower panel reactive antibodies (PRA) at 12 (29.0%vs. 85.5%, p < 0.001) and 24 months (61.0%vs. 91.0%, p = 0.001), reduced risk of high sensitization (PRA ≥90%) at 12 (9.4%vs. 40.7%, p < 0.001, OR = 0.15) and 24 months (25.6%vs. 57.3%, p = 0.001, OR = 0.26) and almost no very high sensitization (PRA ≥ 98%) at 12 months (1.9%vs. 18.6%, p=0.003, OR=0.08) after KAF. In the LWG subgroup analysis, patients who maintained IS for up to 24 months after KAF did not show very high sensitization. The LWG showed shorter active WL times (406vs. 813 days, p = 0.001) without an increased risk of complications. CNI maintenance for at least 12 months after KAF could be a useful approach to prevent high sensitization and reduce WL times in patients who are offered retransplantation, without a higher burden of complications.

Blood collection tube and anticoagulant influence on SARS-CoV-2 antibody and avidity levels

SARS-CoV-2 serology plays a crucial role in assessing COVID-19 vaccine immunogenicity and antibody responses to SARS-CoV-2 infection. Tube type and anticoagulant may influence serology results. Thus, understanding the influence of these variables in test results is key.We evaluated the influence of serum collection tube type and anticoagulant on anti-SARS-CoV-2 spike antibody levels detected by enzyme-linked immunosorbent assays (ELISAs) and Luminex multiplex assays (11-plex) in serum and plasma samples. Anti-spike IgG avidity was also evaluated in both sample types.No significant differences were found between serology assay results using different blood (serum) collection tube types. However, significantly lower antibody concentrations (p < 0.05) were observed in tubes with the anticoagulants sodium citrate and acid citrate dextrose (ACD) in the ELISA and Multiplex assays (n = 29), compared to expected concentrations. These differences mostly disappeared after adjusting for the dilution factor caused by the anticoagulant volume, indicating that anticoagulant does not significantly impact the assay results, while anticoagulant volume does.There was a significant difference (p < 0.05) in IgG avidity (M) of plasma samples (p < 0.05) compared to serum, but anticoagulant type had no effect.Overall, these findings indicate that the choice of collection tube may introduce subtle variations in assay results if the volumes of anticoagulants are not taken into consideration. Additionally, differences between serum and anticoagulant-treated plasma matrices were observed in avidity ELISAs, indicating that these samples are not interchangeable for these assays; a finding that requires further investigation.

Dynamics of Antibody Response to Covishield Vaccine after 6 Months: A Longitudinal Prospective Study.

To study the dynamics of antibody responses in the real world up to 6 months following two Covishield vaccination doses and evaluate its correlation with age. From March 2021 to February 2022, a prospective, longitudinal study of healthcare workers (HCWs) from a dedicated COVID-19 hospital was conducted. Institutional Ethics Committee permission was obtained. HCWs were divided into two groups. The first group consisted of individuals who had received the first dose of the COVID-19 vaccine, with at least 3 weeks elapsed since the dose, and who had not received the second dose until the initial blood sample for antibody testing was obtained. The second group consisted of individuals who had received both COVID-19 doses and had at least 2 weeks between the administration of the second dose and the collection of the first sample for antibody testing. In March 2021, after undergoing phlebotomy for serum collection, the participants responded to the survey. Electrochemiluminescence immunoassay (ECLIA) was used to perform a quantitative test for antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein receptor domain [receptor binding domain (RBD)]. The test used had a 98.8% sensitivity and a 99.9% specificity. If the antibody titer was 0.80 U/mL or higher, it was deemed positive; if it was lower, it was deemed negative. Two follow-ups were conducted for both groups, 3 and 6 months following the first sample collection. During both follow-up visits, a blood sample was obtained for testing the amount of antibody response, and the history of COVID-19 disease following the initial sample was taken. Every HCW had received the Covishield vaccination. After the vaccine's first dosage, 61 HCWs in the first group underwent antibody testing. The information about the 43 HCWs in the first group who attended the two follow-ups is as follows. There were 14 (32.6%) nurses and 5 (11.6%) doctors among the 43 HCWs. The age range was 21-55 years, with the median [interquartile range (IQR)] age being 26 (22-40) years and 20 (60.5%) being females. The vaccination series had a median (IQR) of 34 (29-49) days between doses. There was a statistically significant difference in immunoglobulin G (IgG) levels of the three samples, χ2 = 13.579, p = 0.001. Median (IQR) IgG levels of the three samples at 1 month after the first dose, 3 and 6 months after the second dose were 8511 (51-15400) U/mL, 1471 (249-5050) U/mL, and 978 (220-2854) U/mL, respectively. The antibody titer was negative for two HCWs in the first sample, positive in the rest of the samples, and positive in all samples in both follow-ups. In the second group, following two COVID-19 dosages, a total of 65 HCWs had tested positive for antibodies. The information of the 56 HCWs in group II who attended both follow-ups is as follows. Of the 56 HCWs, 15 (26.8%) were doctors, 27 (48.2%) were nurses, and 14 (25%) were others. The age range was 20-64 years, with a median (IQR) of 29.5 (22-37.7) and 31 (55.3%) female participants. The vaccination series had a median (IQR) interval of 32 (29-35) days between doses. There was a statistically significant difference in IgG levels of the three samples, χ2 = 31.107, p < 0.0001. Median (IQR) IgG levels of the three samples at 20 days, 3.8 months, and 7 months after the second dose were 2377.5, 1345.5, and 1257 U/mL, respectively. Spearman's rank order correlation was used to assess the association between IgG level and age in both groups. The relationship between IgG levels and age was weakly correlated and not statistically significant. There is a waning of antibody titer over time postimmunization. A lower antibody titer can be a contributing factor for infections that emerge later. IgG levels postvaccination do not differ according to age.

Nomogram for predicting the risk of central lymph node metastasis in papillary thyroid microcarcinoma: a combination of sonographic findings and clinical factors.

A considerable controversy over performing thyroidectomy and central lymph node dissection in patients with papillary thyroid microcarcinoma (PTMC) remained. However, accurate prediction of central lymph node metastasis (CLNM) is crucial for surgical extent and proper management. The aim of this study was to develop and validate a practical nomogram for predicting CLNM in patients with PTMC. A total of 1,029 patients with PTMC who underwent thyroidectomy and central lymph node dissection at Tangdu Hospital (the Second Affiliated Hospital of Air Force Medical University) and Xijing Hospital (the First Affiliated Hospital of Air Force Medical University) were selected. Seven hundred and nine patients were assigned to the training set and 320 patients to the validation set. Data encompassing demographic characteristics, ultrasonography results, and biochemical indicators were obtained. Stepwise backward selection and multiple logistic regression were used to screen the variables and establish the nomogram. Concordance index (C-index), receiver operating characteristic (ROC) curve analysis, and decision curve analysis (DCA) were employed to evaluate the nomogram's distinguishability, accuracy, and clinical utility. Young age, multifocality, bigger tumor, presence of microcalcification, aspect ratio (height divided by width) ≥1, loss of fatty hilum, high free thyroxine (FT4), and lower anti-thyroid peroxidase antibody (TPOAb) were significantly associated with CLNM. The nomogram showed strong predictive capacity, with a C-index and accuracy of 0.784 and 0.713 in the training set and 0.779 and 0.703 in the external validation set, respectively. DCA indicated that the nomogram demonstrated strong clinical applicability. We established a reliable, cost-effective, reproducible, and noninvasive nomogram for predicting CLNM in patients with PTMC. This tool could be a valuable guidance for deciding on management in PTMC.

Efficacy, effectiveness and immunogenicity of reduced HPV vaccination schedules: A review of available evidence.

Current National Advisory Committee on Immunization (NACI) guidance recommends human papillomavirus (HPV) vaccines be administered as a two or three-dose schedule. Recently, several large clinical trials have reported the clinical benefit of a single HPV vaccine dose. As a result, the World Health Organization released updated guidance on HPV vaccines in 2022, recommending a two-dose schedule for individuals aged 9-20 years, and acknowledging the use of an alternative off-label single dose schedule. The objective of this overview is to provide a detailed account of the available evidence comparing HPV vaccination schedules, which was considered by NACI when updating recommendations on HPV vaccines. To identify relevant evidence, existing systematic reviews were leveraged where possible. Individual studies were critically appraised, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence. Available evidence suggests that a one, two, or three-dose HPV vaccine schedule may provide similar protection from HPV infection. While antibody levels against HPV vaccine types were statistically significantly lower with a single dose schedule compared to two or three doses, titres were sustained for up to 16 years. The clinical significance of lower antibody titres is unknown, as there is no established immunologic correlate of protection. While the available evidence on single-dose HPV vaccination schedules shows a one-dose schedule is highly effective, continued follow-up of single-dose cohorts will be critical to understanding the relative duration of protection for reduced dose schedules and informing future NACI guidance on HPV vaccines.

Comparison of Hepatitis B Surface Antibody Levels After Vaccination With Combined One Dose of Hexavalent Vaccine and Two Doses of Pentavalent Vaccine Versus Three Doses of Pentavalent Vaccine.

Vaccination can effectively prevent hepatitis B virus (HBV) infection. Vaccination with 3 doses of hexavalent HBV-containing vaccines led to a higher Hepatitis B surface antibody (anti-HBs) antibody level than vaccination with 3 doses of pentavalent HBV-containing vaccines. Whether the substitution of one dose of hexavalent HBV-containing vaccine in the pentavalent regimen could lead to a higher anti-HBs antibody level remains unknown. A randomized, open-label controlled trial was conducted. Infants aged 30-120 days were randomly assigned to either a combined hexavalent/pentavalent regimen (hexavalent HBV-containing vaccine at 2 months of age and pentavalent HBV-containing vaccine at 4 and 6 months of age) or a 3-dose pentavalent regimen (pentavalent HBV-containing vaccine at 2, 4, and 6 months of age). Anti-HBs antibody levels were measured 3-6 months after the last vaccination. Seventy-six infants were enrolled, 38 in each group. The geometric mean of anti-HBs antibody levels in the combined hexavalent/pentavalent group was significantly higher than that of the 3-dose pentavalent group [316.2 mIU/mL (95% CI: 173.8-575.4 mIU/mL) versus 81.3 mIU/mL (95% CI: 38.9-169.8 mIU/mL), P = 0.006]. By multivariate analysis, the combined hexavalent/pentavalent regimen (coefficient 0.57; P = 0.003) was associated with higher anti-HBs antibody levels, while body weight <10th percentile (coefficient -0.85; P = 0.006) and receiving concomitant pneumococcal conjugated vaccines (coefficient -0.65; P = 0.001) were associated with lower anti-HBs antibody levels. Substituting the first dose with a hexavalent HBV-containing vaccine in the pentavalent regimen for HBV vaccination led to higher anti-HBs antibody levels in infants. Concomitant pneumococcal conjugated vaccine administration may have an adverse impact on anti-HBs antibody level.

Differences in SARS-CoV-2 antibodies depending on age, blood group, and sex in a Swedish blood donor cohort

This study aimed to describe differences in prevalence and the long-term presence of nucleocapsid antibodies (N-antibodies) elicited by SARS-CoV-2 infection in a Swedish blood donor population not subjected to lockdown. We tested 20,651 blood donor samples for nucleocapsid antibodies from the beginning of March 2020 and 27 months onwards using the Roche Elecsys Anti-SARS-CoV-2 assay. The proportion of positive SARS-CoV-2 antibody samples was determined each week. After the exclusions of one-time donors and subjects with incomplete data, 19,726 samples from 4003 donors remained. Differences in antibody prevalences stratified for age, sex, and blood groups (ABO and RhD) were determined, as well as antibody loss and recovery. Lower antibody prevalence was seen for older donors, blood group AB, and RhD-negative subjects. A significant decrease in antibody titer between the first and the second antibody-positive donation was seen for the whole study group, females, older subjects, blood group O, AB, and RhD-positive subjects. The titer waned below the detection limit in 60 (3.0%) of 1983 N-antibody-positive donors, and for 18 of these donors, a second episode with antibodies was detected. We showed that N-antibodies persist for months or years and that surprisingly few antibody-positive donors lost their antibodies. We also conclude that antibody prevalence in a Swedish population never subject to lockdown did not apparently differ from populations that were subject to stricter regulations.

Humoral immune response and safety of Sars-Cov-2 vaccine in people with multiple sclerosis

BackgroundFor the past three years, the pandemic has had a major effect on global public health, mainly on those with underlying medical conditions, such as people living with Multiple Sclerosis. Vaccination among this group is of great importance, and the long-term impacts of vaccination and its safety on the health of these patients will continue to be revealed. Therefore, risks related to vaccination and immune response need to be assessed. The objective here was to characterize the immune response, short-term safety, and the effects of multiple variables on these factors after COVID-19 vaccination (mainly Sinopharm) among people with Multiple Sclerosis. We assessed the short-term safety and humoral SARS-COV-2 anti-RBD IgG response using a data collection form and Immunoassay, respectively.ResultsNo severe adverse events or MS relapse was observed. Myalgia/body pain (26.7%), low-grade fever (22.2%), and mild headache (15.6%) were the most common adverse events. The use and type of vaccine influenced the frequency of side effects with a p-value < 0.0001. Regarding immune response, patients on rituximab and fingolimod had a lower antibody titer compared to other medications. With a significant difference, hybrid immunity (p-value: 0.047) and type of DMTs (p-value: 0.017) affected the humoral response.ConclusionThere is a low incidence of serious adverse effects, MS worsening or relapse after COVID-19 vaccination, and mainly, side effects are similar to that of the general population. It appears that treatment with various disease-modifying therapies does not induce or worsen the post-vaccination side effects, although some, including Rituximab and fingolimod, may affect the immunity induced after vaccination.

Immunogenicity of COVID-19 vaccines in patients with follicular lymphoma receiving frontline chemoimmunotherapy.

Immune responses to primary COVID-19 vaccination were investigated in 58 patients with follicular lymphoma (FL) as part of the PETReA trial of frontline therapy (EudraCT 2016-004010-10). COVID-19 vaccines (BNT162b2 or ChAdOx1) were administered before, during or after cytoreductive treatment comprising rituximab (depletes B cells) and either bendamustine (depletes CD4+ T cells) or cyclophosphamide-based chemotherapy. Blood samples obtained after vaccine doses 1 and 2 (V1, V2) were analysed for antibodies and T cells reactive to the SARS-CoV-2 spike protein using the Abbott Architect and interferon-gamma ELISpot assays respectively. Compared to 149 healthy controls, patients with FL exhibited lower antibody but preserved T-cell responses. Within the FL cohort, multivariable analysis identified low pre-treatment serum IgA levels and V2 administration during induction or maintenance treatment as independent determinants of lower antibody and higher T-cell responses, and bendamustine and high/intermediate FLIPI-2 score as additional determinants of a lower antibody response. Several clinical scenarios were identified where dichotomous immune responses were estimated with >95% confidence based on combinations of predictive variables. In conclusion, the immunogenicity of COVID-19 vaccines in FL patients is influenced by multiple disease- and treatment-related factors, among which B-cell depletion showed differential effects on antibody and T-cell responses.

Longitudinal humoral analysis in RSV-infected infants identifies pre-existing RSV strain-specific G and evolving cross-reactive F antibodies

Respiratory syncytial virus (RSV) is among the most common causes of lower respiratory tract infection (LRTI) and hospitalization in infants. However, the mechanisms of immune control in infants remain incompletely understood. Antibody profiling against attachment (G)and fusion (F)proteins in children less than 2 years of age, with mild (outpatients) or severe (inpatients) RSV disease, indicated substantial age-dependent differences in RSV-specific immunity. Maternal antibodies were detectable for the first 3months of life, followed by a long window of immune vulnerability between 3 and 6months and a rapid evolution of FcγR-recruiting immunity after 6months of age. Acutely ill hospitalized children exhibited lower G-specific antibodies compared with healthy controls. With disease resolution, RSV-infected infants generated broad functional RSV strain-specific G-responses and evolved cross-reactive F-responses, with minimal maternal imprinting. These data suggest an age-independent RSV G-specific functional humoral correlate of protection, and the evolution of RSV F-specific functional immunity with disease resolution.

Heterotypic immunity from prior SARS-CoV-2 infection but not COVID-19 vaccination associates with lower endemic coronavirus incidence.

Immune responses from prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 vaccination mitigate disease severity, but they do not fully prevent subsequent infections, especially from genetically divergent strains. We examined the incidence of and immune differences against human endemic coronaviruses (eCoVs) as a proxy for response against future genetically heterologous coronaviruses (CoVs). We assessed differences in symptomatic eCoV and non-CoV respiratory disease incidence among those with known prior SARS-CoV-2 infection or previous COVID-19 vaccination but no documented SARS-CoV-2 infection or neither exposure. Retrospective cohort analyses suggest that prior SARS-CoV-2 infection, but not previous COVID-19 vaccination alone, associates with a lower incidence of subsequent symptomatic eCoV infection. There was no difference in non-CoV incidence, implying that the observed difference was eCoV specific. In a second cohort where both cellular and humoral immunity were measured, those with prior SARS-CoV-2 spike protein exposure had lower eCoV-directed neutralizing antibodies, suggesting that neutralization is not responsible for the observed decreased eCoV disease. The three groups had similar cellular responses against the eCoV spike protein and nucleocapsid antigens. However, CD8+ T cell responses to the nonstructural eCoV proteins nsp12 and nsp13 were higher in individuals with previous SARS-CoV-2 infection as compared with the other groups. This association between prior SARS-CoV-2 infection and decreased incidence of eCoV disease may therefore be due to a boost in CD8+ T cell responses against eCoV nsp12 and nsp13, suggesting that incorporation of nonstructural viral antigens in a future pan-CoV vaccine may improve vaccine efficacy.

A 20-year serological survey of Toxoplasma gondii and Neospora caninum infection in dogs with neuromuscular disorders from urban areas in Argentina

Toxoplasma gondii and Neospora caninum infections may be associated with neuromuscular disorders in dogs. The aim of this study was to assess the seroprevalence to these protozoan parasites in dogs with neuromuscular disease from urban areas of Buenos Aires province, Argentina, over a period of 20 years, and to evaluate the association of seropositivity and antibody titres with different variables such as sex, breed and age. For this, a total of 7238 serum samples from urban owned dogs were analysed by the indirect fluorescence antibody test (IFAT) for specific IgG antibodies. The observed seropositivity rates were 35.7 % for T. gondii and 25.7 % for N. caninum. Crossbred dogs had a significantly higher seroprevalence for T. gondii than purebred dogs (41 % vs. 29.3 %), while a trend towards significance was observed for N. caninum, which was slightly higher in purebred dogs (26 % vs. 23.6 %). Seroprevalence for both parasites increased with age and was higher in older animals. Regarding the distribution of specific antibody titres, the most frequent IFAT T. gondii titre found was 100 and for N. caninum it was ≥800. For toxoplasmosis, there was no association with age group, and low titres (50, 100 and 200) predominated in all groups. However, for neosporosis, age and titres were significantly associated for one age group, with dogs under 12 months of age having a higher proportion of high titres (400 and 800). The trend in the seroprevalence for T. gondii is increasing over the years and lower antibody titres predominate in the dogs studied, which may be more related to the presence of chronic infections and not necessarily to the clinical signs of the animals. Despite the generally low titres observed for toxoplasmosis in this study, it is important to highlight the high seroprevalence found in our region, as dogs can act as sentinels of environmental contamination and as indicators of possible human infection. In the case of neosporosis, although the trend in seroprevalence in dogs with signs appears to be decreasing over the years, our work shows that higher antibody titres predominate, and are probably related to the clinical signs presented by the dogs. This study provides the most recent epidemiological data and serological profiles of T. gondii and N. caninum infections in a large number of canine sera from urban areas in Argentina, providing relevant information for clinical veterinarians and epidemiologists in order to understand the circulation of the parasites.

Immune responses and reinfection of SARS-CoV-2 Omicron variant in patients with lung cancer.

A significant Omicron wave emerged in China in December 2022. To explore the duration of humoral and cellular response postinfection and the efficacy of hybrid immunity in preventing Omicron reinfection in patients with lung cancer, a total of 447 patients were included in the longitudinal study after the Omicron wave from March 2023 to August 2023. Humoral responses were measured at pre-Omicron wave, 3 months and 7 months postinfection. The detected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific antibodies including total antibodies, anti-receptor binding domain (RBD) specific IgG, and neutralizing antibodies against SARS-CoV-2 wild type (WT) and BA.4/5 variant. T cell responses against SARS-CoV-2 WT and Omicron variant were evaluated in 101 patients by ELISpot at 3 months postinfection. The results showed that Omicron-infected symptoms were mild, while fatigue (30.2%), shortness of breath (34.0%) and persistent cough (23.6%) were long-lasting, and vaccines showed efficacy against fever in lung cancer patients. Humoral responses were higher in full or booster vaccinated patients than those unvaccinated (p < .05 for all four antibodies), and the enhanced response persisted for at least 7 months. T cell response to Omicron was higher than WT peptides (21.3 vs. 16.0 SFUs/106 PBMCs, p = .0093). Moreover, 38 (9.74%) patients were reinfected, which had lower antibody responses than non-reinfected patients (all p < .05), and those patients of unvaccinated at late stage receiving anti-cancer immunotherapy alone were at high risk of reinfection. Collectively, these data demonstrate the Omicron infection induces a high and durable immune response in vaccinated patients with lung cancer, which protects vaccinated patients from reinfection.

Immunological Insights: A Multicenter Longitudinal Study on Humoral Response to COVID-19 Vaccines in Greece

Vaccination has emerged as the most effective tool in the battle against COVID-19. To optimize vaccination protocols, a deeper understanding of the immune response to vaccination, including influential factors and its duration, is essential. This study aimed to assess the humoral response in vaccinated individuals with or without prior SARS-CoV-2 infection. A prospective observational study was conducted across 14 private healthcare structures in Greece. Anti-spike IgG titers were measured at different timepoints following the initial vaccination and booster doses of the BNT162b2, mRNA-1273, ChAdOx1 nCoV-19, and Ad26.COV2.S vaccines. A total of 505 participants were included in the first phase, evaluating the humoral response after the initial vaccination, and 311 participants were involved in the second phase, assessing the effects of booster vaccination. All vaccines elicited high anti-S IgG titers initially, followed by a subsequent decline that was addressed by the booster vaccination. The humoral response was sustained up to one year after the booster vaccination. mRNA vaccines induced higher anti-S IgG titers compared to vector vaccines, with mRNA-1273 eliciting higher titers than BNT162b2. Vaccination resulted in higher antibody titers than natural infection alone; however, convalescent patients who received vaccination had significantly higher anti-S IgG titers compared to those who received the booster vaccine without previous SARS-CoV-2 infection. Lower antibody titers were observed in men and older patients (&gt;51.5 years old), as well as smokers, although the decline rate was lower in these subgroups. These results underscore the importance of booster doses and reveal the potential influence of age, gender, smoking habits, and vaccine type on varying humoral responses. Long-term monitoring of antibody persistence, evaluation of cellular immune responses, and assessment of vaccine efficacy against emerging variants should be considered to enhance our understanding of immunity dynamics and inform vaccine development and deployment strategies.