Browsing by Subject "ANTIBODIES"

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  • Jalkanen, Pinja; Pasternack, Arja; Maljanen, Sari; Melen, Krister; Kolehmainen, Pekka; Huttunen, Moona; Lundberg, Rickard; Tripathi, Lav; Khan, Hira; Ritvos, Mikael A.; Naves, Rauno; Haveri, Anu; Österlund, Pamela; Kuivanen, Suvi; Jääskeläinen, Anne J.; Kurkela, Satu; Lappalainen, Maija; Rantasärkkä, Kaisa; Vuorinen, Tytti; Hytönen, Jukka; Waris, Matti; Tauriainen, Sisko; Ritvos, Olli; Kakkola, Laura; Julkunen, Ilkka (2021)
    Background. Primary diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is based on detection of virus RNA in nasopharyngeal swab samples. In addition, analysis of humoral immunity against SARS-CoV-2 has an important role in viral diagnostics and seroprevalence estimates. Methods. We developed and optimized an enzyme immunoassays (EIA) using SARS-CoV-2 nucleoprotein (N), Si and receptor binding domain (RBD) of the viral spike protein, and N proteins from SARS, Middle East respiratory syndrome (MERS), and 4 low-pathogenic human CoVs. Neutralizing antibody activity was compared with SARS-CoV-2 IgG, IgA, and IgM EIA results. Results. The sensitivity of EIA for detecting immune response in COVID-19 patients (n = 101) was 77% in the acute phase and 100% in the convalescent phase of SARS-CoV-2 infection when N and RBD were used as antigens in IgG and IgA specific EIAs. SARS-CoV-2 infection significantly increased humoral immune responses against the 229E and NL63 N proteins. Si and RBD-based EIA results had a strong correlation with microneutralization test results. Conclusions. The data indicate a combination of SARS-CoV-2 Si or RBD and N proteins and analysis of IgG and IgA immunoglobulin classes in sera provide an excellent basis for specific and sensitive serological diagnostics of COVID-19.
  • Amanat, Fatima; Stadlbauer, Daniel; Strohmeier, Shirin; Nguyen, Thi H. O.; Chromikova, Veronika; McMahon, Meagan; Jiang, Kaijun; Arunkumar, Guha Asthagiri; Jurczyszak, Denise; Polanco, Jose; Bermudez-Gonzalez, Maria; Kleiner, Giulio; Aydillo, Teresa; Miorin, Lisa; Fierer, Daniel S.; Lugo, Luz Amarilis; Kojic, Erna Milunka; Stoever, Jonathan; Liu, Sean T. H.; Cunningham-Rundles, Charlotte; Felgner, Philip L.; Moran, Thomas; Garcia-Sastre, Adolfo; Caplivski, Daniel; Cheng, Allen C.; Kedzierska, Katherine; Vapalahti, Olli; Hepojoki, Jussi M.; Simon, Viviana; Krammer, Florian (2020)
    Development of an enzyme-linked immunosorbent assay to detect antibodies to the SARS-CoV-2 spike protein in human sera and plasma. Here, we describe a serological enzyme-linked immunosorbent assay for the screening and identification of human SARS-CoV-2 seroconverters. This assay does not require the handling of infectious virus, can be adjusted to detect different antibody types in serum and plasma and is amenable to scaling. Serological assays are of critical importance to help define previous exposure to SARS-CoV-2 in populations, identify highly reactive human donors for convalescent plasma therapy and investigate correlates of protection.
  • Karjalainen, Erno; Izquierdo, Diana F.; Marti-Centelles, Vicente; Luis, Santiago V.; Tenhu, Heikki; Garcia-Verdugo, Eduardo (2014)
  • Reusken, Chantal; Boonstra, Marrit; Rugebregt, Sharona; Scherbeijn, Sandra; Chandler, Felicity; Avsic-Zupanc, Tatjana; Vapalahti, Olli; Koopmans, Marion; GeurtsvanKessel, Corine H. (2019)
    Background: Tick-borne encephalitis (TBE) is an infectious disease endemic to large parts of Europe and Asia. Diagnosing TBE often relies on the detection of TBEV-specific antibodies in serum and cerebrospinal fluid (CSF) as viral genome is mostly not detectable once neurological symptoms occur. Objectives: We evaluated the performance of TBEV IgM and IgG ELISAs in both serum and CSF of confirmed TBEV patients and discuss the role of (CSF) serology in TBEV diagnostics. Study design: For the assay evaluation we collected specimen from confirmed TBEV patients. Assay specificity was assessed using sera from patients with a related flavivirus infection or other acute infection. A selected ELISA assay was used to analyze TBEV-specific antibodies in CSF and to evaluate the use in confirming TBE diagnosis. Results: In this study the overall sensitivity of the IgM TBEV ELISAs was acceptable (94-100 %). Four out of five IgM ELISA's demonstrated an excellent overall specificity from 94-100% whereas a low overall specificity was observed for the IgG TBEV ELISAs (30-71%). Intrathecal antibody production against TBEV was demonstrated in a subset of TBE patients. Conclusions: In four out of five ELISAs, IgM testing in serum and CSF of TBE patients is specific and confirmative. The lack of IgG specificity in all ELISAs emphasizes the need of confirmatory testing by virus neutralisation, depending on the patient's background and the geographic location of exposure to TBEV. A CSF-serum IgG antibody index can support the diagnosis specifically in chronic disease or once IgM has disappeared.
  • Hetemaki, Iivo; Jarva, Hanna; Kluger, Nicolas; Baldauf, Hanna-Mari; Laakso, Sini; Bratland, Eirik; Husebye, Eystein S.; Kisand, Kai; Ranki, Annamari; Peterson, Part; Arstila, T. Petteri (2016)
    Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a monogenic autoimmune disease caused by mutations in the AIRE gene. Although mainly an endocrine disease, a substantial fraction of patients have gastrointestinal manifestations. In this study, we have examined the role of anticommensal responses and their regulation. APECED patients had increased levels of Abs against Saccharomyces cerevisiae (p <0.0001) and against several species of commensal gut bacteria, but not against species predominantly associated with other locations. The anticommensal Ab levels did not correlate with gastrointestinal autoantibodies, neutralizing anti-IL-17 or -IL-22 Abs, or gastrointestinal symptoms, although scarcity of the available clinical data suggests that further study is required. However, the anti-S. cerevisiae Ab levels showed a significant inverse correlation with FOXP3 expression levels in regulatory T cells (Treg), previously shown to be dysfunctional in APECED. The correlation was strongest in the activated CD45RO(+) population (rho = 20.706; p <0.01). APECED patients also had decreased numbers of FOXP3(+) cells in gut biopsies. These results show that APECED patients develop early and sustained responses to gut microbial Ags in a pattern reminiscent of Crohn's disease. This abnormal immune recognition of gut commensals is linked to a systemic Treg defect, which is also reflected as a local decrease of gut-associated Treg. To our knowledge, these data are the first to show dysregulated responses to non-self commensal Ags in APECED and indicate that AIRE contributes to the regulation of gut homeostasis, at least indirectly. The data also raise the possibility of persistent microbial stimulation as a contributing factor in the pathogenesis of APECED.
  • Vaarala, Outi; Vuorela, Arja; Partinen, Markku; Baumann, Marc; Freitag, Tobias L.; Meri, Seppo; Saavalainen, Paivi; Jauhiainen, Matti; Soliymani, Rabah; Kirjavainen, Turkka; Olsen, Paivi; Saarenpaa-Heikkila, Outi; Rouvinen, Juha; Roivainen, Merja; Nohynek, Hanna; Jokinen, Jukka; Julkunen, Ilkka; Kilpi, Terhi (2014)
  • Veijola, Lea Irene; Oksanen, Aino Mirjam; Sipponen, Pentti Ilmari; Rautelin, Hilpi Iris Kaarina (2010)
  • Luo, Guo; Ambati, Aditya; Lin, Ling; Bonvalet, Melodie; Partinen, Markku; Ji, Xuhuai; Maecker, Holden Terry; Mignot, Emmanuel Jean-Marie (2018)
    Type 1 narcolepsy (T1N) is caused by hypocretin/orexin (HCRT) neuronal loss. Association with the HLA DQB1*06:02/DQA1*01:02 (98% vs. 25%) heterodimer (DQ0602), T cell receptors (TCR) and other immune loci suggest autoimmunity but autoantigens are unknown. Onset is seasonal and associated with influenza A, notably pandemic 2009 H1N1 (pH1N1) infection and vaccination (Pandemrix). Peptides derived from HCRT and influenza A, including pH1N1, were screened for DQ0602 binding and presence of cognate DQ0602 tetramer-peptide-specific CD4(+) T cells tested in 35 T1N cases and 22 DQ0602 controls. Higher reactivity to influenza pHA(273-287) (pH1N1 specific), PR8 (H1N1 pre-2009 and H2N2)-specific NP17-31 and C-amidated but not native version of HCRT54-66 and HCRT86-97 (HCRTNH2) were observed in T1N. Single-cell TCR sequencing revealed sharing of CDR3 beta TRBV4-2-CASSQETQGRNYGYTF in HCRTNH2 and pHA(273-287)-tetramers, suggesting molecular mimicry. This public CDR3 beta uses TRBV4-2, a segment modulated by T1N-associated SNP rs1008599, suggesting causality. TCR-alpha/beta CDR3 motifs of HCRT54-66-NH2 and HCRT86-97-NH2 tetramers were extensively shared: notably public CDR3 alpha, TRAV2-CAVETDSWGKLQF-TRAJ24, that uses TRAJ24, a chain modulated by T1N-associated SNPs rs1154155 and rs1483979. TCR-alpha/beta CDR3 sequences found in pHA(273-287), NP17-31, and HCRTNH2 tetramer-positive CD4(+) cells were also retrieved in single INF-gamma-secreting CD4(+) sorted cells stimulated with Pandemrix, independently confirming these results. Our results provide evidence for autoimmunity and molecular mimicry with flu antigens modulated by genetic components in the pathophysiology of T1N.
  • Habibullah, Mahmoud; Porter, Julie A.; Kluger, Nicolas; Ranki, Annamari; Krohn, Kai J. E.; Brandi, Maria L.; Brown, Edward M.; Weetman, Anthony P.; Kemp, E. Helen (2018)
    A major manifestation of autoimmune polyendocrine syndrome type 1 (APS1) is hypoparathyroidism, which is suggested to result from aberrant immune responses against the parathyroid glands. The calcium-sensing receptor (CaSR), which plays a pivotal role in maintaining calcium homeostasis by sensing blood calcium levels and regulating release of parathyroid hormone (PTH), is an autoantibody target in APS1. In this study, the aim was to characterize the binding sites, specificity, functional affinity, IgG subclass, and functional effects of CaSR autoantibodies using phage-display technology, ELISA, and bioassays. The results indicated that CaSR autoantibody binding sites were at aa 41-69, 114-126, 171-195, and 260-340 in the extracellular domain of the receptor. Autoantibodies against CaSR epitopes 41-69, 171-195, and 260-340 were exclusively of the IgG1 subclass. Autoantibody responses against CaSR epitope 114-126 were predominantly of the IgG1 with a minority of the IgG3 subclass. Only autoantibodies recognizing CaSR epitopes 114-126 and 171-195 affected receptor activity; inositol-phosphate accumulation was increased significantly in HEK293-CaSR cells, and PTH secretion from PTH-C1 cells was reduced significantly when either were incubated with purified Ab and Ca2+ compared with Ca2+ alone. In conclusion, although the majority of APS1 patients do not have CaSR-stimulating autoantibodies, the hypoparathyroid state in a small minority of patients is the result of functional suppression of the parathyroid glands.
  • Qiu, Tianyi; Yang, Yiyan; Qiu, Jingxuan; Huang, Yang; Xu, Tianlei; Xiao, Han; Wu, Dingfeng; Zhang, Qingchen; Zhou, Chen; Zhang, Xiaoyan; Tang, Kailin; Xu, Jianqing; Cao, Zhiwei (2018)
    Major challenges in vaccine development include rapidly selecting or designing immunogens for raising cross-protective immunity against different intra-or inter-subtypic pathogens, especially for the newly emerging varieties. Here we propose a computational method, Conformational Epitope (CE)-BLAST, for calculating the antigenic similarity among different pathogens with stable and high performance, which is independent of the prior binding-assay information, unlike the currently available models that heavily rely on the historical experimental data. Tool validation incorporates influenza-related experimental data sufficient for stability and reliability determination. Application to dengue-related data demonstrates high harmonization between the computed clusters and the experimental serological data, undetectable by classical grouping. CE-BLAST identifies the potential cross-reactive epitope between the recent zika pathogen and the dengue virus, precisely corroborated by experimental data. The high performance of the pathogens without the experimental binding data suggests the potential utility of CE-BLAST to rapidly design cross-protective vaccines or promptly determine the efficacy of the currently marketed vaccine against emerging pathogens, which are the critical factors for containing emerging disease outbreaks.
  • Valtonen, Ville (2017)
    A great variety of non-specific symptoms may occur in patients living or working in moisture-damaged buildings. In the beginning, these symptoms are usually reversible, mild, and present irritation of mucosa and increased morbidity due to respiratory tract infections and asthma-like symptoms. Later, the disease may become chronic and a patient is referred to a doctor where the assessment of dampness and mold hypersensitivity syndrome (DMHS) often presents diagnostic challenges. Currently, unanimously accepted laboratory tests are not yet available. Therefore, the diagnosis of DMHS is clinical and is based on the patient's history and careful examination. In this publication, I reviewed contemporary knowledge on clinical presentations, laboratory methods, and clinical assessment of DMHS. From the literature, I have not found any proposed diagnostic clinical criteria. Therefore, I propose five clinical criteria to diagnose DMHS: (1) the history of mold exposure in water-damaged buildings, (2) increased morbidity to due infections, (3) sick building syndrome, (4) multiple chemical sensitivity, and (5) enhanced scent sensitivity. If all the five criteria are met, the patient has a very probable DMHS. To resolve the current problems in assigning correct DMHS diagnosis, we also need novel assays to estimate potential risks of developing DMHS.
  • Ronnberg, Bengt; Gustafsson, Ake; Vapalahti, Olli; Emmerich, Petra; Lundkvist, Ake; Schmidt-Chanasit, Jonas; Blomberg, Jonas (2017)
    The recent spread of Zika virus (ZIKV) in the Americas and Asia necessitates an increased preparedness for improved maternal and perinatal health and blood safety. However, serological cross-reactions, especially to Dengue virus (DENV), complicate ZIKV antibody serodiagnosis. A novel "pan-Flavi" suspension multiplex immunoassay (PFSMIA) using 25 antigens, whole virus (WV), non-structural protein 1 (NS1), and envelope (E) proteins, from 7 zoonotic flaviviruses for specific detection of ZIKV and DENV IgM and IgG was developed. Patterns of antibody cross-reactivity, avidity, and kinetics were established in 104 sera from returning travelers with known ZIKV and DENV infections. PFSMIA gave IgM- and IgG-sensitivities for both viruses of 96-100%, compared to an immunofluorescence assay. Main IgM cross-reactions were to NS1, for IgG to the E and WV antigens. Infecting virus yielded reactivity to several antigens of the homologous virus, while cross-reactions tended to occur only to a single antigen from heterologous virus(es). A specificity-enhancing computer procedure took into account antibody isotype, number of antibody-reactive antigens per virus, avidity, average degree of cross-reactivity to heterologous flavivirus antigens, and reactivity changes in serial sera. It classified all 50 cases correctly. Applied to sera from 200 pregnant women and 173 blood donors from Sweden, one blood donor was found ZIKV NS1 IgM positive, and another as ZIKV NS1 IgG positive. These samples did not react with other ZIKV antigens and were thereby judged as false-positives. PFSMIA provided sensitive and specific ZIKV and DENV serology, warranting high-throughput serological surveillance and a minimized need for laborious and expensive virus neutralization assays.
  • Haller-Kikkatalo, Kadri; Alnek, Kristi; Metspalu, Andres; Mihailov, Evelin; Metskula, Kaja; Kisand, Kalle; Pisarev, Heti; Salumets, Andres; Uibo, Raivo (2017)
    The presence of autoantibodies usually precedes autoimmune disease, but is sometimes considered an incidental finding with no clinical relevance. The prevalence of immune-mediated diseases was studied in a group of individuals from the Estonian Genome Project (n = 51,862), and 6 clinically significant autoantibodies were detected in a subgroup of 994 (auto) immune-mediated disease-free individuals. The overall prevalence of individuals with immune-mediated diseases in the primary cohort was 30.1%. Similarly, 23.6% of the participants in the disease-free subgroup were seropositive for at least one autoantibody. Several phenotypic parameters were associated with autoantibodies. The results suggest that (i) immune-mediated diseases are diagnosed in nearly one-third of a random European population, (ii) 6 common autoantibodies are detectable in almost one-third of individuals without diagnosed autoimmune diseases, (iii) tissue non-specific autoantibodies, especially at high levels, may reflect preclinical disease in symptom-free individuals, and (iv) the incidental positivity of anti-TPO in men with positive familial anamnesis of maternal autoimmune disease deserves further medical attention. These results encourage physicians to evaluate autoantibodies in addition to treating a variety of patient health complaints to detect autoimmune-mediated disease early.
  • Virtanen, Jenni; Aaltonen, Kirsi; Vapalahti, Olli; Sironen, Tarja (2020)
    Aleutian disease (AD), caused by Aleutian mink disease virus (AMDV), causes significant welfare problems to mink, and financial losses to the farmers. As there is no vaccine or treatment available, reliable diagnostics is important for disease control. Here, we set up a probe-based real-time PCR (NS1-probe-PCR) to detect all strains of AMDV. PCR was validated and compared to two other real-time PCR methods (pan-AMDV- and pan-AMDO-PCR) currently used for AMDV diagnostics in Finland. The NS1-probe-PCR had a similar detection limit of 20 copies/reaction based on plasmid dilution series, and similar or better diagnostic sensitivity, when evaluated using spleen samples from mink, and stool samples from mink and foxes. None of the three PCR tests cross-reacted with other parvoviruses. The NS1-probe-PCR also showed a significantly higher specificity than the pan-AMDO-PCR with spleen samples and the best specificity with stool samples. Furthermore, it produced the results more rapidly than the other two PCRs making it a promising tool for both diagnostic and research purposes.
  • Mueller, Janis A.; Harms, Mirja; Schubert, Axel; Mayer, Benjamin; Jansen, Stephanie; Herbeuval, Jean-Philippe; Michel, Detlef; Mertens, Thomas; Vapalahti, Olli; Schmidt-Chanasit, Jonas; Muench, Jan (2017)
    Zika virus (ZIKV) is an emerging pathogen that causes congenital infections which may result in birth defects, such as microcephaly. Currently, no approved treatment or vaccination is available. ZIKV can be readily detected in cell culture where virally infected cells are normally stained by specific antibodies. As ZIKV regularly causes a cytopathic effect, we were wondering whether this viral property can be used to quantitatively determine viral infectivity. We here describe the use of an 3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide-(MTT)-based cell viability assay that allows to determine ZIKV-induced cell death. We show that this colorimetric assay quantifies ZIKV infection over a broad range of viral dilutions in both monkey and human cells. It allows to determine inhibitory activities of antivirals that block ZIKV or to define the neutralizing antibody titers of ZIKV antisera. This MTT-based ZIKV detection assay can be evaluated by naked eye or computational tools, has a broad linear range, does not require large equipment or costly reagents, and thus represents a promising alternative to antibody-based assays, in particular in resource-poor settings. We propose to use this simple, fast, and cheap method for quantification of ZIKV neutralizing antibodies and testing of antiviral compounds.
  • Lammi, Anne; Arikoski, Pekka; Hakulinen, Arja; Schwab, Ursula; Uusitupa, Matti; Heinonen, Seppo; Savilahti, Erkki; Kinnunen, Tuure; Ilonen, Jorma (2016)
    Objective. The development of gliadin-specific antibody and T-cell responses were longitudinally monitored in young children with genetic risk for celiac disease (CD). Material and methods. 291 newborn children positive for HLA-DQB1*02 and -DQA1*05 alleles were followed until 3-4 years of age by screening for tissue transglutaminase autoantibodies (tTGA) by using a commercial ELISA-based kit and antibodies to deamidated gliadin peptide (anti-DGP) by an immunofluorometric assay. Eighty-five of the children were also followed for peripheral blood gliadin-specific CD4(+) T-cell responses by using a carboxyfluorescein diacetate succinimidyl ester-based in vitro proliferation assay. Results. The cumulative incidence of tTGA seropositivity during the follow-up was 6.5%. CD was diagnosed in nine of the tTGA-positive children (3.1%) by duodenal biopsy at a median 3.5 years of age. All of the children with confirmed CD were both IgA and IgG anti-DGP positive at the time of tTGA seroconversion and in over half of the cases IgG anti-DGP positivity even preceded tTGA seroconversion. Peripheral blood T-cell responses to deamidated and native gliadin were detected in 40.5% and 22.2% of the children at the age of 9 months and these frequencies decreased during the follow-up to the levels of 22.2% and 8.9%, respectively. Conclusions. Anti-DGP antibodies may precede tTGA seroconversion and thus frequent monitoring of both tTGA and anti-DGP antibodies may allow earlier detection of CD in genetically susceptible children. Peripheral blood gliadin-specific T-cell responses are relatively common in HLA-DQ2-positive children and are not directly associated with the development of CD.
  • Pöllänen, Petra M.; Ryhänen, Samppa J.; Toppari, Jorma; Ilonen, Jorma; Vähäsalo, Paula; Veijola, Riitta; Siljander, Heli; Knip, Mikael (2020)
    Context: We set out to characterize the dynamics of islet autoantibodies over the first 15 years of life in children carrying genetic susceptibility to type 1 diabetes (T1D). We also assessed systematically the role of zinc transporter 8 autoantibodies (ZnT8A) in this context. Design: HLA-predisposed children (N = 1006, 53.0% boys) recruited from the general population during 1994 to 1997 were observed from birth over a median time of 14.9 years (range, 1.9-15.5 years) for ZnT8A, islet cell (ICA), insulin (IAA), glutamate decarboxylase (GADA), and islet antigen-2 (IA-2A) antibodies, and for T1D. Results: By age 15.5 years, 35 (3.5%) children had progressed to T1D. Islet autoimmunity developed in 275 (27.3%) children at a median age of 7.4 years (range, 0.3-15.1 years). The ICA seroconversion rate increased toward puberty, but the biochemically defined autoantibodies peaked at a young age. Before age 2 years, ZnT8A and IAA appeared commonly as the first autoantibody, but in the preschool years IA-2A- and especially GADA-initiated autoimmunity increased. Thereafter, GADA-positive seroconversions continued to appear steadily until ages 10 to 15 years. Inverse IAA seroconversions occurred frequently (49.3% turned negative) and marked a prolonged delay from seroconversion to diagnosis compared to persistent IAA (8.2 vs 3.4 years; P = .01). Conclusions: In HLA-predisposed children, the primary autoantibody is characteristic of age and might reflect the events driving the disease process toward clinical T1D. Autoantibody persistence affects the risk of T1D. These findings provide a framework for identifying disease subpopulations and for personalizing the efforts to predict and prevent T1D.
  • Diabimmune Study Grp; Simre, Kart; Uibo, Oivi; Hämäläinen, Anu-Maaria; Härkönen, Taina; Siljander, Heli; Virtanen, Suvi M.; Ilonen, Jorma; Hyöty, Heikki; Knip, Mikael (2019)
    Aim Our aim was to compare the presence of various common viruses (rhinovirus, enterovirus, adenovirus, Epstein-Barr virus, cytomegalovirus, norovirus, parechovirus) in stool and nasal swab samples as well as virus-specific antibodies in serum samples between children who developed coeliac disease and controls. Methods A case-control study was established based on the DIABIMMUNE Study cohorts. During the study, eight Estonian children and 21 Finnish children aged 1.5 years to five years developed coeliac disease and each was matched with a disease-free control. Nasal swabs and stool samples were taken at the age of three to six months and the serum samples at the time of diagnosis. Results Rhinovirus ribonucleic acid was detected in the nasal swabs from five coeliac disease children, but none of the control children (p = 0.05). There were no statistically significant differences in the level of viral antibodies between cases and controls. Enterovirus immunoglobulin G class antibodies were found more frequently in the Estonian than in the Finnish children (63% versus 23%, p = 0.02). Conclusion This study did not find any marked overall differences in laboratory-confirmed common viral infections between the children who developed coeliac disease and the controls. However, rhinovirus infections were detected slightly more often in those patients who developed coeliac disease.
  • Nokireki, Tiina; Jakava-Viljanen, Miia; Virtala, Anna-Maija; Sihvonen, Liisa (2017)
    Background: Rabies is preventable by pre-and/or post-exposure prophylaxis consisting of series of rabies vaccinations and in some cases the use of immunoglobulins. The success of vaccination can be estimated either by measuring virus neutralising antibodies or by challenge experiment. Vaccines based on rabies virus offer cross-protection against other lyssaviruses closely related to rabies virus. The aim was to assess the success of rabies vaccination measured by the antibody response in dogs (n = 10,071) and cats (n = 722), as well as to investigate the factors influencing the response to vaccination when animals failed to reach a rabies antibody titre of = 0.5 IU/ml. Another aim was to assess the level of protection afforded by a commercial veterinary rabies vaccine against intracerebral challenge in mice with European bat lyssavirus type 2 (EBLV-2) and classical rabies virus (RABV), and to compare this with the protection offered by a vaccine for humans. Results: A significantly higher proportion of dogs (10.7%, 95% confidence interval CI 10.1-11.3) than cats (3.5%; 95% CI 2.3-5.0) had a vaccination antibody titre of <0.5 IU/ml. In dogs, vaccination with certain vaccines, vaccination over 6 months prior the time of antibody determination and vaccination of dogs with a size of > 60 cm or larger resulted in a higher risk of failing to reach an antibody level of at least 0.5 IU/ml. When challenged with EBLV-2 and RABV, 80 and 100% of mice vaccinated with the veterinary rabies vaccine survived, respectively. When mice were vaccinated with the human rabies vaccine and challenged with EBLV-2, 75-80% survived, depending on the booster. All vaccinated mice developed sufficient to high titres of virus-neutralising antibodies (VNA) against RABV 21-22 days post-vaccination, ranging from 0.5 to 128 IU/ml. However, there was significant difference between antibody titres after vaccinating once in comparison to vaccinating twice (P <0.05). Conclusions: There was a significant difference between dogs and cats in their ability to reach a post vaccination antibody titre of = 0.5 IU/ml. Mice vaccinated with RABV-based rabies vaccines were partly cross-protected against EBLV-2, but there was no clear correlation between VNA titres and cross-protection against EBLV-2. Measurement of the RABV VNA titre can only be seen as a partial tool to estimate the cross-protection against other lyssaviruses. Booster vaccination is recommended for dogs and cats if exposed to infected bats.
  • Sane, Famara; Bertin, Antoine; Sioofy-Khojine, Amir-Babak; Oikarinen, Sami; Alidjinou, Enagnon K.; Veijola, Riitta; Toppari, Jorma; Ilonen, Jorma; Knip, Mikael; Engelmann, Ilka; Hyöty, Heikki; Hober, Didier (2020)
    Abstract Studies in prospective cohorts have suggested that enterovirus infections are associated with the appearance of islet autoantibodies that precede later appearance of type 1 diabetes (T1D). It was shown that in addition to an antibody-mediated anti-coxsackievirus (CV)-B neutralizing activity of serum from patients with T1D, there was also enhancing anti-CV-B activity in vitro. In this study the patterns of enhancing and neutralizing anti-CV activities were analyzed from consecutive serum samples collected from children who were followed from birth until they developed T1D in the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) study and compared to those in non-diabetic control children. The titers of serum neutralizing activity were analyzed against those CVs which were detected in the stools in these children (CV-B3, CV-B5 or CV-A4) using plaque assay. The enhancing activity of these serum samples was analysed by measuring interferon-alpha (INF-α) production in cultures of peripheral blood mononuclear cells (PBMC) inoculated with a mixture of these viruses and diluted serum. A sustained anti-CV enhancing activity was observed in consecutive serum samples in patients with T1D. The pattern of responses differed between children who developed T1D and control children. In patients, the anti-CV enhancing activity was predominant or even exclusive over the neutralizing activity, whereas in controls the enhancing and neutralizing activities were more balanced or the neutralizing activity was largely predominant. In conclusion, evaluating the anti-enterovirus neutralizing and enhancing activity of serum samples can be useful to investigate further the relationship between enteroviruses and the development of T1D. This article is protected by copyright. All rights reserved.