Significant Decrease In Antibody Titers Research Articles

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 and Cellular Responses to COVID-19 Vaccination Indicate the Need for Post-Vaccination Testing in Frail Population.

Despite the high efficacy of the BNT162b2 vaccine in the general population, data on its immunogenicity among frail elderly individuals are limited. Recently, levels of anti-SARS-CoV-2 spike IgG antibodies and serum neutralization titers were confirmed as good immune markers of protection against the virus, with evidence showing a reverse correlation between these two parameters and susceptibility to infection. Here we analyzed sera from 138 nursing home residents (median age of 88.9 years) and 312 nursing home staff (median age of 50.7 years) to determine the humoral response to two doses of the BNT162b2 vaccine, and found markedly decreased serum anti-spike antibody levels and neutralization titers in the nursing home resident (NHR) group, with over 11% non-responders compared to only 1.3% among the controls. Moreover, three months post-vaccination, a significant decrease in antibody titers was observed in COVID-19-naive nursing home residents. Subsequent flow cytometry and interferon gamma secretion analyses indicated that antibody non-responders among NHRs also failed to mount cellular responses. The presented data emphasize that additional measures are needed in the population of frail elderly individuals. Given the high proportion of non-responders among NHRs, continued monitoring should be considered in this group.

Effects of nano-manganese on humoral immune response and oxidative stress in broilers

The objective of the present study was to evaluate the alterations in selected indicators of immune responses and oxidative stress of broilers fed with nano-manganese. One hundred-sixty 1-day-old broiler chicks were randomly assigned into four groups with three replicates. Birds were fed the same basal diet supplemented with nano-manganese oxide, as 0.00 (control group), 50.00, 100, or 150 mg kg-1 of diet. The birds were vaccinated against avian influenza (AI), Newcastle disease (ND), infectious bronchitis (IB) and infectious bursal disease (IBD) as the standard vaccination schedule. Blood sample was taken from the brachial vein of birds on 42th day. A significant decrease in antibody titer against sheep RBC was revealed in the nano-manganese 100 and 150 groups compared to the control group. In addition, the antibody titers against IB and ND were significantly lower in the all nano-manganese groups compared to the control group. No significant difference was observed for the antibody titer against AI and oxidative stress indices among the experimental groups. The findings in the present study suggested that nano-manganese at 50.00, 100 and 150 mg kg-1 levels might suppress humoral immune response in broilers which should be taken into consideration in supplementation.

Post-treatment human papillomavirus antibody kinetics in cervical cancer patients.

Antibodies to the E6 and E7 oncoproteins of high-risk human papillomavirus (HPV) types are strongly associated with HPV-driven cancer, while antibodies against the capsid protein L1 are considered cumulative exposure markers. To test the hypothesis that L1 antibody levels are stable over time, whereas E6 and E7 levels undergo decay after cervical cancer (CxCa) treatment, we performed multiplex serology for HPV16 and 18 antigens E6, E7 and L1 in a post-treatment study of 184 patients with invasive CxCa that were characterized with a median follow-up time of 725 days, and 2-12 sera per patient. Antibody titers significantly decreased within the first six months for HPV16 E6 and E7 but not L1, and stabilized for the following 12 months on a high level, with few patients showing seroreversion. Of 67 patients seropositive for HPV16 E6 at diagnosis, 28 (41.8%) showed a decrease in antibody titers of at least 50% within the first 18 months. Similarly, of 50 HPV16 E7 seropositives, 33 (66.0%) showed decreasing antibody levels, whereas antibody decay was less frequent for HPV16 L1 (12 of 47, 25.5%). Using a power-law mathematical model to characterize antibody decay kinetics, the mean (±s.e.) durations to a 50% reduction in antibody titers within individual patients were estimated to be 56.9 (±26.1) and 56.3 (±19.0) days for HPV16 E6 and E7, respectively. In summary, HPV16 E6 and E7 antibodies undergo a slow but significant decrease in antibody titers within the first 6-18 months following CxCa treatment. However, larger studies are needed to confirm the utility of serology for prediction of disease progression and time to relapse based on antibody decay kinetics. This article is part of the theme issue 'Silent cancer agents: multi-disciplinary modelling of human DNA oncoviruses'.

P076 Alloantibody desensitization outcomes: PRA levels, CPRA or antibody titers; how to use them best

Aim Desensitization protocols that include IVIG, plasmapheresis have been utilized by multiple groups with different levels of success. More recently, Rituximab and Bortezomib have been studied as part of desensitization therapies, but the data to support the utility and safety of these agents to reduce PRA is still debatable. This retrospective IRB approved study, looked at patients listed at Tampa General Hospital from 10/2011 to 10/2014. These patients were categorized into 3 different groups: non sensitized, sensitized non treated and sensitized treated. Sensitization was defined as a Percent Reactive Antibody (PRA) > 10%. The aim of this study was to evaluate the effects of PRA and HLA antibody specificity and titers, to best evaluate the efficacy of treatment. Methods % Class I and II PRA was measured by Flow PRA beads and antibody specificity/titers, using Luminex SAB (One Lambda, Canoga Park, CA). Results From 10/2011 to 10/2014, 164 heart transplant patients were listed for transplantation. Fifteen of the 58 sensitized patients (25.9%) underwent desensitization therapy. Patients on desensitization, all received plasmapheresis and IVIG, with a median of 3 monthly cycles. Eleven of the 15 patients (73.3%) also received Rituximab therapy. Two of the 15 (13.3%) received Bortexomib therapy after at least 2 cycles of plasmapheresis, IVIG and Rituximab with no significant decrease in HLA antibody by any of the methods tested. Twelve out of the 15 patients (80%) were transplanted. Eight out of 15 (53%) of patients showed no significant change in antibody reduction if %PRA or cPRA were utilized as end points. However, 12 out of 15 (80%) patients that proceeded to transplant after desensitization had a significant decrease in antibody titers. Conclusions When reporting the effects of desensitization therapy, the use of %PRA and/or cPRA can be deceiving and can possibly result in the misinterpretation of the efficacy of protocols among different transplant centers. The utilization of titers was the most reliable way to proceed to transplant. Patients that were transplanted after the desensitization protocol (80%) have shown no significant difference from non- sensitized patients in antibody mediated rejection (p 0.05) and have not developed significant DSA after transplant.

Fall in antibody titer to small ruminant lentivirus in the periparturient period in goats

The prospective study was carried out to document the change of antibody level to small ruminant lentivirus (SRLV) in chronically infected pregnant does. Thirteen dairy goats of Polish White Improved and Polish Fawn Improved breeds, asymptomatically infected with SRLV for at least a year, were enrolled. The goats were blood-sampled at mating, then four times during pregnancy, 2 weeks before kidding, at kidding and monthly for three months postpartum. Antibody titers to SRLV were determined by screening sera in increasing dilutions with three different commercial ELISAs: indirect whole-virus antigen (wELISA), indirect p28-transmembrane antigen (p28-TM-ELISA) and competitive gp135 (SU-ELISA). Then, the reciprocal of the greatest dilution at which a serum yielded the result greater than the cut-off of the test was considered the end-point antibody titer. Compared to the level at mating antibody titers significantly fell at kidding in all three tests. Significant decrease in antibody titer was observed for the longest time in SU-ELISA and for the shortest time in p28-TM-ELISA. At kidding false negative results were observed in two ELISAs (p28-TM-ELISA and SU-ELISA) and 3 of 13 goats became seronegative at kidding in at least one ELISA. At least four-fold fall in antibody titer between mating and kidding was observed in wELISA in 6 goats, in p28-TM-ELISA in 4 goats and in SU-ELISA in 5 goats. None of goats showed at least four-fold decrease in all three tests. Fall in antibody titer to SRLV in the periparturient period can interfere with the results of serological screening of pregnant goats.

Some Chemical Pollutants of Water Used in Broiler Chicken Farms and Their Effect on Immune Response and Body Weight of Chicken

The chemical fitness of water used in so me broiler farms in Behera and Kafr El sheikh Provinces was assessed and effects of some of the detected chemical pollutants on the body weight and the immune response of broiler chicken to so me vaccines including New castle disease (ND) and infectious bursal disease (IBD) vaccines were studied. A total of 100 water samples were co llected including; 71 water samples fro m chicken farms (44 samp les fro m underground water and 27 fro m tap water) and 29 water samples were collected fro m streams and canals located at the same areas of chicken farms. Chemical examination was performed at The Central Laboratory, Faculty of Agriculture, Kafr El Sheikh Un iversity to determine the levels of lead, iron, copper, zinc, manganese, cadmiu m and cobalt. The obtained results revealed detection of lead, copper, iron, zinc, manganese in some of the examined sample and their maximu m concentration were 0.23, 0.67, 2.15, 7.75, 2.99 mg/l, respectively while cadmiu m and cobalt could not be detected in all samples. The effects of the detected chemical pollutants on the body weight and the immune response of broiler chicken to so me vaccines were evaluated. 195 one day old broiler chicks were randomly selected and divided in to 6 groups (each group contains two sub groups; each sub group contains 15 chicks), that were received water with selected chemical pollutants including lead, iron, copper, zinc and manganese and one group containing 15 ch icks was reared as a control group that received distilled water. All the experimental groups was vaccinated against ND and IBD then the antibody titers of ND and IBD vaccines was measured by the Heamagglutination Inhibit ion Test (HI test) and En zy me linked Immunosorbent Assay (ELISA), respectively. The obtained results revealed that the group of chicks received water containing the low and high levels of lead showed a significant decrease in antibody titer when co mpared with control g roup. Also, the group received treated water with high level of copper showed a significant decrease in the antibody titer of ND at days 21 and 28 when co mpared with control group. Results of ELISA showed a significant decrease in antibody titer of IBD at day 21 in the group received water containing the high dose of copper. By co mparing the final body weight of all groups, it was observed that there was a significant decrease in the body weight of groups received high level of lead and high level of all po llutants together. On the other hand, there was a significant increase in the body weight of the group received high level of zinc. Finally, it was concluded that lead and copper had an adverse effect on the immune response of broiler chicken and their body weight so periodical examination of water for presence of chemical pollutant especially heavy metals is suggested.

Immunogenicity of Heptavalent Conjugate Vaccine Against Streptococcus pneumoniae in Premature Babies with Low Birth Weight

There are few studies about immunogenicity and safety of heptavalent pneumococcal-CRM197 conjugate vaccine (PCV7) in low birth weight infants. Assessment of immunogenicity following administration of PCV7 in low birth weight children. The PCV7 vaccine was administered to 60 infants divided into two groups: 23 children with birth weight <1000g (Group I); and 37 children with birth weight ≥1000g (Group II). Serum was collected four times. Birth weight of children included in the study ranged from 480g to 2450g. The primary immunization caused an increase in the average concentration of antibodies for all serotypes in most of the participants, with no significant differences between the groups. However, there were some differences between various serotypes. Group serotypes 6B and 23F were the least immunogenic (≥0.35μg/mL, Group I vs. Group II - 6B: 78.3% vs. 67,6% p=0.371 and 23F: 87% vs. 83.8% p=0.738). Prior to the administration of a booster dose, a significant decrease in antibody titer was observed in all children. The last vaccination resulted in an increased concentration of antibodies in all children in both groups, and the results were significantly higher compared to those measured following administration of three doses of the vaccine. PCV7 is immunogenic in children with low, very low, and extremely low birth weight. Serotypes 6B and 23F were the least immunogenic, and serotype 14 proved to be the most immunogenic.

Respuesta inmunitaria a la vacuna de la hepatitis B en pacientes hemodializados en Brasil y sus factores asociados

Patients on chronic hemodialysis have a lower immune response to vaccination against hepatitis B virus (HBV) than the general population. To identify factors that may interfere with immunization against hepatitis B virus (HBV) in Brazilian hemodialysis patients and analyze the evolution of the level of antibodies. A retrospective longitudinal study, using records of patients on hemodialysis in the years 2000-2008. Non-responder patients, defined as a level of anti-HBs less than 10 IU/mL, were identified. The effect of social and demographic factors, clinical and laboratory data on the lack of response was evaluated. Logistic regression analysis was used to assess the independent effect of each factor. The difference between initial and final anti-HBs levels (24 months), was also analyzed. Fifty seven percent of patients responded adequately to vaccination. After adjustment with other variables, the only factor associated with immune response was serum ferritin. Responding patients of less than 40 years of age did not have a significant decrease in antibody titers over time. The initial anti-HBs title, influenced the final title. Fifty percent of non-responders achieved serum levels of protection after revaccination. The study showed that ferritin may be a marker of reduced immune response. Patients aged less than 40 years were the only ones who maintained over time their initial anti-HBs levels.

The Presence of Moderate to High Donor-Specific Anti-HLA Antibody Titers Is Associated with a High Risk of Graft Failure in Haploidentical Stem Cell Transplantation

Background and Rationale: Stem cell transplantation using alternative sources of stem cells from haploidentical relatives is an established therapy for high risk leukemia patients who lack a matched related or unrelated donor. Although efforts have been made to improve the engraftment rate in haploidentical stem cell transplantation, approximately 10–20% of these patients fail to achieve primary engraftment. The causes for this higher rate of graft failure are currently unknown. We hypothesized that anti-HLA antibodies directed against donor specific antigens (DSA) are a possible cause for graft failure in such patients.Materials and Methods: Twenty-two consecutive patients who received a T-cell depleted haploidentical graft at our institution after 9/2005 were evaluated prospectively for presence of DSA. The patients received a conditioning regimen consisting of fludarabine, melphalan and thiotepa previously described, and megadoses of CD34+ cells. The presence of antibodies against DSA was determined by testing the patients' sera with a panel of fluorescent beads coated with single HLA antigen preparations using a Luminex™ platform; results were interpreted as fluorescence intensity (FI) against DSA mismatch. FI less then 500 was considered negative, while positive FI ranging 500–1500, 1500–3000 and >3000 were classified as weak, intermediate and strong, respectively. HLA A, B, C, DRB1, DRB3/4/5, DQB1 and DPB1 were typed by high resolution methods.Results: Of the 22 treated patients, 6 experienced primary graft failure (PGF). Five of these patients, all females with median age 39 years (range 26–50), were identified to have intermediate or strong FI anti DSA. The anti-HLA antibodies identified were directed against both HLA class I and II antigens, most commonly anti-HLA DRB1 (Table 1). After the first patient was identified to have graft failure in the presence of DSA, treatment with rituximab and plasma exchange was initiated in an attempt to decrease DSA titers and achieve engraftment. Subsequently, four patients were treated in this fashion, two of which had a significant decrease in antibody titers and achieved engraftment. The remaining 2 patients experienced also PGF. All 3 patients who had PGF underwent a second transplant from the same donors. In one of these patients who experienced two graft losses, the DSA was strong before the first transplant decreased significantly a few days after transplantation and returned to the intermediate FI range before the second transplant. Overall, 4 of 6 (67%) haploidentical transplants performed in the in the presence of DSA, and 4 of 4 (100%) transplants performed in patients with moderate to high DSA titers failed to achieve engraftment. Rituximab and plasma exchange appeared to decrease the DSA in 2 of 4 patients with moderate titers, enough to allow engraftment (Table 1). No significant differences were found in the number of CD34+ cells infused, number of allele mismatched, and number of bone marrow blasts present at the time of transplant between the PGF and the control group. The fact that all patients with DSA were females prompted a review of the pregnancy history. The median number of pregnancies was 3 in the PGF group (N=5) as compared with 0 in the control group (N=6) (P=0.1). In addition, a review of the transfusion history to explain a possible alloimmunization at least in one patient without prior pregnancies, identified a median of 37 units (range 17–65) transfused in the PGF group (N=5) as compared with 15 the control group (range 4–38) (N=16) (P=0.007).Conclusion: Donor specific anti-HLA antibodies appear to play an important role in preventing engraftment in patients receiving a (T-cell depleted) haploidentical stem cell transplant.Figure 1. Relationship between HLA antibody titers and engraftment in 5 patients who received a total of eight haploidentical transplants at MDACC.Pt #AB typeInitial titerR/PETiter after R/PE/pre first SCTEngrafted Y/NTiter after first SCT/Pre second SCTEngrafted Y/N1A*3201N/AN+ + +NNTY2A*0211+ + +Y+ +N+ +NB*391301+ + ++ ++ + +Cw*0702+ + +NTNTDRB1*0404+++3DRB1*0701+ +Y-YN/AN/ADRB1*0701+ ++ + +-4DRB4*0101+ + +Y+ + +N-YDQB1*0202+ + ++ + +-DRB1*0401+ ++/− (borderline)5DRB4*0103+ +Y+YN/AN/ADPB1*0401+ + ++ + +Legend: AB – antibody, R – rituximab, PE – plasma exchange, NT – not tested

Diagnostic value of serum antibodies in early Pseudomonas aeruginosa infection in cystic fibrosis patients

Specific serum antibodies could be helpful in defining the status of Pseudomonas aeruginosa infection as well as the response to early intervention treatment in patients with cystic fibrosis (CF). We used 1,791 serum samples from 375 European CF patients with known respiratory microbiology status to define titers of P. aeruginosa antibodies directed against alkaline protease (AP), elastase (ELA), and exotoxin A (ExoA). Pseudomonas antibody titers were also measured in a separate cohort of 56 patients undergoing antibiotic treatment for eradication of P. aeruginosa. At a specificity of 97.5%, the sensitivity was highest for antibodies against AP (85.4%), followed by ELA (76.2%) and ExoA (72.0%). AP, ELA, or ExoA antibody titers were significantly higher (P < 0.001) in patients chronically infected with P. aeruginosa compared to patients with negative cultures. The sensitivity of the combined three ELISAs was higher than that for any single ELISA alone. Based on the newly defined cut-off levels, positive serum antibody titers against at least one of the three antigens were present in 43% of patients with new onset of P. aeruginosa infection. Longitudinal assessment of antibody titers assessed before and after inhaled antibiotic therapy in patients with first P. aeruginosa isolation showed a significant decrease in antibody titers against AP and ExoA in patients clearing P. aeruginosa infection, whereas titers increased in patients in whom antibiotic therapy failed to eradicate the organism. Antibody testing against AP, ELA, and ExoA offers high sensitivity and specificity for the presence of P. aeruginosa in respiratory cultures of CF patients. Although serum antibody titers are on average low at the time of first P. aeruginosa isolation from respiratory specimens, they may be useful to monitor response to therapy. However, because variability between patients is considerable, treatment decisions should not be based on P. aeruginosa antibody levels alone.

Targeting Notch Signaling as a Safe and Effective Treatment for Autoimmune and Lymphoproliferative Diseases.

Patients and mice with both the autoimmune lymphoproliferative syndrome (ALPS) and systemic lupus erythematosis (SLE) have T cell dysregulation and produce both abnormal, activated T lymphocytes and an unusual T cell population, Double Negative T cells (DNTs, cell phenotype: CD3+, CD4-, CD8-, TCR αβ+). The Notch signaling pathway is important in T cell lineage development, including development of DNTs, and in T cell activation. Inhibitors of this pathway are in clinical development, because inhibiting Notch signaling may be effective in treating Alzheimer's disease and T cell leukemia. We hypothesized that inhibiting Notch signaling would be effective in reducing symptoms and treating the disease in patients with ALPS and SLE by both reducing the production of abnormal DNTs and by blocking aberrant T cell activation. We tested this hypothesis using two murine models of defective lymphocyte apoptosis, CBA-lprcg and MRL-lpr. CBA-lprcg has a phenotype similar to human ALPS, as these mice develop massive lymphadenopathy and splenomegaly with DNT infiltration of these organs. In the MRL-lpr background, the apoptotic defect manifests itself in a phenotype similar to human SLE, as these mice develop autoantibodies, glomerulonephritis, and a vasculitic dermatitis. Mice were randomized to treatment with a low dose (5mg/kg/day) of the α-secretase inhibitor, DAPT, for 5 days a week by gavage versus vehicle. Treatment response was followed with assessment of DNTs in peripheral blood and lymphoid tissue by flow cytometry, by monitoring of lymph node and spleen size with small animal ultrasound, and ELISA to quantify antibody titer for anti-dsDNA IgG specific antibodies. We found a profound and statistically significant decrease in antibody titer (p = 0.02), lymphadenopathy (p = 0.006), and splenomegaly (p = 0.008) after only 4 weeks, comparing mice treated with DAPT to control animals (Table). Treated mice also had decreased absolute DNTs in their spleens (p = 0.02) and lymph nodes (p = 0.04) compared to control. Treated mice had a trend toward decreased absolute DNTs in peripheral blood; however, more animals are being enrolled on this study to reach 80% power to detect a statistically significant difference. Finally, treated MRL-lpr mice showed stabilization or improvement in their characteristic vasculitic skin disease, whereas control animals showed progression. We found the response to DAPT was durable, having treated mice for over 12 weeks. Also, with this dosing schema, mice experienced no toxicity. They did not manifest any gastrointestinal symptoms, as have been reported with other γ-secretase inhibitors. In summary, inhibiting the Notch signaling pathway appears to be a safe and well-tolerated means of treating autoimmune and lymphoproliferative diseases. This is the first report to use γ-secretase inhibitors to treat non-malignant, T-lymphocyte mediated disease.Disease Parameter(1)DAPT Treated(2)Vehicle Control(2)p valueLymph node volume by ultrasound (mm3)360 (170–550)780 (366–1043)p = 0.006Splenic area by ultrasound (mm2)48 (27–73)159 (69–336)p = 0.008anti-dsDNA IgG antibody titer (ug/ml)450 (340–560)1350 (1260–1410)p = 0.02(1) Averge antibody titer, volume of lymph nodes, and area of spleens were similar and not statistically different between groups at initiation of treatment; (2) average (range) after 4 weeks of treatment

Virus Reactivation Profile as Assessed by PCR and Serology Pattern Following First-Line Alemtuzumab (Anti-CD52 Monoclonal Antibody, Campath®) Therapy in Patients with B-CLL.

Alemtuzumab (Campath®) has shown promising results in the treatment of B-cell chronic lymphocytic leukemia (B-CLL) as first-line therapy and in fludarabine-refractory disease (Lundin, Blood 2002; Keating, Blood 2002). Alemtuzumab induces depletion of all lymphoid subsets, which may persist for a prolonged period of time (Lundin, Leukemia 2004). As a result, an increased risk of infection has been associated with alemtuzumab therapy, in particular cytomegalovirus (CMV) reactivation causing symptomatic disease in 10%–30% of patients. It is of importance, therefore, to study the incidence of clinical and subclinical reactivation of not only CMV but also other pathogenic viruses, as well as serology patterns, in order to better understand the consequences of the induced immunosuppression and to further evaluate the safety of alemtuzumab therapy in B-CLL patients. In this study, serum samples were analyzed from 18 patients with B-CLL who achieved long-lasting unmaintained remissions following first-line alemtuzumab SC therapy (Lundin, Blood 2002). Quantitative real time PCR was used to detect and measure the presence of CMV, Ebstein-Barr virus (EBV), human herpesvirus-6 (HHV-6), and parvovirus B19. Analyses were conducted at the following timepoints: baseline; Months 1, 2, and 3 of alemtuzumab therapy; end of treatment; 6 and 12 months post-alemtuzumab therapy. The presence of serum immunoglobulin G (IgG) antibodies against CMV, varicella-zoster (VZV), Morbillivirus, Epstein-Barr Nuclear Antigen-1 (EBNA1) protein of EBV, and Streptococcus pneumoniae were detected by Enzyme-Linked Immunosorbent Assay (ELISA), and EBV viral capsid antigen (VCA) IgG by immunofluorescence (IF). All 18 patients with B-CLL responded (PR or CR) to alemtuzumab therapy. Median time to treatment failure was 34 months (range, 9–71+). There were 9 episodes of viral reactivation (5 CMV after 1–2 months of therapy; 3 EBV at baseline; 1 HHV-6 after 1 month of therapy) measured by PCR in 8 patients (44%) during the study period. The median number of genome equivalents/mL was 2,600 (range, 1,300–81,400). A retrospective analysis of the case records revealed that 3/5 episodes of CMV reactivation correlated to discrete clinical symptoms (transient, grade I fever or temporary cough), which were not diagnosed as viremia during the clinical part of the study. All 9 episodes of viral reactivation resolved spontaneously, except for 1 patient (in stable unmaintained PR) who had a late recurrence of symptomatic EBV infection 20 months after completion of alemtuzumab therapy. The viral load and symptoms responded to rituximab (anti-CD20 monoclonal antibody, Rituxan®) therapy, but repeated treatment episodes have been required. Most patients had stable IgG reactivities during and after alemtuzumab therapy; however, 6 patients (35%) had a significant decrease in antibody titers: 4 against Morbillivirus and 2 against EBV. These results suggest that virus reactivation is not uncommon in patients receiving alemtuzumab therapy for B-CLL. Notably, most reactivations occurred early during therapy, were asymptomatic or caused discrete symptoms, and usually resolved spontaneously without specific therapy. Additional studies on virus reactivation and long-term studies of virus serology to evaluate the need for vaccination are warranted also in patients with fludarabine-refractory B-CLL receiving alemtuzumab.

Double-dose accelerated hepatitis B vaccine in patients with end-stage liver disease.

The aims of this study are to assess the efficacy of hepatitis B virus (HBV) vaccination using an accelerated schedule and double dose of recombinant vaccine in liver transplant recipients and identify factors associated with seroconversion and persistence of antibody to hepatitis B surface antigen (anti-HBs). Three hundred fifty-six patients were enrolled. Exclusion criteria were previous HBV infection, fulminant liver failure, or less than 2 years of follow-up after orthotopic liver transplantation (OLT). The vaccination schedule was 0, 2 weeks, 4 weeks, and 6 months using double-dose recombinant vaccine. Seroconversion was evaluated prospectively by measuring anti-HBs on the day of OLT and 1 and 2 years after OLT. Quantitative analyses of anti-HBs were performed retrospectively on stored sera. Geometric mean concentrations (GMCs) were calculated using a standard formula. All patients completed the full vaccination schedule, and 129 patients (36%) completed the schedule before OLT. The overall prevalence of anti-HBs was 128 of 356 pre-OLT samples (36%) compared with 41 of 353 (11.6%) and 26 of 325 post-OLT samples (8%) 1 and 2 years after OLT, respectively (both P =.001). The pre-OLT GMC was 86.7 compared with 0.32 and 0.33 at 1 and 2 years after OLT, respectively (P =.001). Patients with high titers of anti-HBs before OLT were more likely to have persistence of antibodies 1 or 2 years after OLT. Younger age (P =.02), low Child-Pugh score (P =.02), underlying chronic hepatitis C (P=.03), and specific host HLA subtypes were most strongly associated with seroconversion and/or persistence of anti-HBs. Thus, (1) seroconversion before or after OLT using double-dose accelerated-schedule vaccination against HBV is low, (2) there is a rapid, significant decrease in antibody titer after OLT, (3) pre-OLT anti-HBs titer potentially may be useful in predicting persistence of protective antibodies after OLT, and (4) several factors (age, genetic predisposition, severity of liver disease, and underlying liver disease) may have a role in poor vaccine responsiveness.

Longevity of naturally acquired antibody responses to the N- and C-terminal regions of Plasmodium vivax merozoite surface protein 1.

In an earlier study, we found that individuals with patent infection had significantly higher IgG antibody titers to the 19-kD C-terminal region of Plasmodium vivax merozoite surface protein 1 (PvMSP1) than individuals treated for malaria 1-4 months earlier. These results suggested that the antibody levels decreased rapidly following treatment. The present study was designed to determine the persistence of antibody response to the N- and C-terminal regions of PvMSP1 after infection with P. vivax in individuals from the city of Bélem in northern Brazil. Our results demonstrated that the vast majority of individuals had a significant decrease in antibody titers to the C-terminal region of PvMSP1 in a period of two months following treatment. Among responders to the C-terminal region, 44.4% became serologically negative and 44.4% had their antibody titers reduced by an average of 13-fold. Only 11.2% of the individuals had their antibody titers maintained or slightly increased during that period. A decrease in the antibody response to the recombinant protein representing the N-terminal region of PvMSP1 was also noted; however, it was not as dramatic. The rapid decrease in the antibody levels to the C-terminal region of PvMSP1 might contribute to the high risk of reinfection in these individuals.

Suppression of murine collagen-induced arthritis with monoclonal anti-Ia antibodies and augmentation with IFN-gamma.

Collagen-induced arthritis (CIA) is an experimental model in which a specific immune response to type II collagen (CII) is associated with the development of inflammatory arthritis. In this study, we evaluated the effects of early and delayed treatments with anti-Ia mAb and IFN-gamma on murine CIA. Administration of anti-Ia mAb at the time of immunization with CII decreased the incidence and delayed the onset of arthritis, whereas anti-Ia treatments begun 2 wk after immunization had no effect upon either arthritis incidence or onset. Neither treatment protocol resulted in a significant decrease in antibody titer or proliferative response to CII. Because IFN-gamma increases Ia expression in a variety of cells, we determined its effect on arthritis incidence and onset. When IFN-gamma treatments were begun at the time of immunization the incidence of arthritis was increased and arthritis onset was more rapid. Treatment with IFN-gamma did not result in an increase in anti-CII antibody levels. These results support the importance of Ia expression in the induction of murine collagen-induced arthritis, and suggest that suppression with anti-Ia antibodies and augmentation with IFN-gamma are not the result of changes in the humoral response to CII, but may be due to local effects within the target organ.

Two-year follow-up of rubella vaccinees in a public school system.

Two years after receiving live rubella virus vaccine, 625 school children were retested to determine the persistence of vaccine-induced antibody. There was no significant change in antibody between seven weeks and two years after vaccination in 307 of 313 Cendehill strain vaccinees and 282 of 299 high passaged virus (HPV)-77-dog kidney (DK)-12 strain vaccinees. Five Cendehill and 6 HPV-77-DK-12 vaccinees experienced a significant decrease in antibody titer, and one Cendehill and 11 HPV-77-DK-12 vaccinees experienced a significant increase in titer. Thirteen children were revaccinated; one had a significant boost in antibody titer. Among a control group of susceptible adolescent girls not vaccinated, 86 of 93 remained susceptible. Two control girls had clinical and five had subclinical rubella. Medical and laboratory surveillance revealed little rubella in the school system during the two-year period.

Candida-Reacting Antibody in the Serum of Patients with Lymphomas and Related Disorders

Abstract 1. The quantity and characteristics of antibody reacting with Candida albicans was determined in normal subjects and in patients with lymphomas and leukemias by the immune-adherence technic. 2. Little antibody to Candida albicans is present in infants during the first few months of neonatal life; a progressive increase in antibody occurs during adolescence, and antibody is present in high titer in the serum of normal adults. 3. No significant decrease in antibody titer was found in the sera of patients with advanced leukemia or lymphoma, most of whom had had extensive specific therapy. 4. This antibody was characterized by lack of cross absorption with rice starch polysaccharide, complete absorption with Candida albicans and by increased serum reactivity following active antigenic stimulation in rabbits. 5. It is apparent from this study that production of the "natural antibody" of this type is maintained despite the progression of neoplastic disease and the use of antineoplastic agents. 6. It is probable that alteration of tissue defense mechanisms rather than humoral antibody account for the increased incidence of disseminated monilial infections in patients with lymphomas and leukemias.