Articoli di riviste: "Antibody avidity"

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Arifa, Julian Eva, Budiman Bela, Silvia Tri Widyaningtyas e Jeanne Elvia Christian. "Penggunaan antigen p24, IDR-Gp41 dan ID2-Pol dalam uji aviditas untuk identifikasi kasus baru pada infeksi HIV-1". Jurnal Biotek Medisiana Indonesia 8, n. 1 (18 dicembre 2019): 1–8. http://dx.doi.org/10.22435/jbmi.v8i1.2578.

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AIDS is a severe immunodeficiency disease caused by HIV. Identification of new HIV infection in a population is required for the evaluation of intervention strategy of HIV-1 transmission. The avidity assay has been promoted for HIV-1 detection. Avidity assay is based on affinity strength of the epitopes of the HIV antigen against its specific corresponding antibodies. The binding of the antigen - the antibody formed in the initial phase of infection is relatively weak and easy to break with chaotropic reagents. In contrary, the antigen-antibody binding formation in long-term infection is strong and not easily broken by addition of chaotropic reagents. Commercial avidity assays are available, however the antigens used might not be compatible with the circulating HIV strains in Indonesia. AbstractThis research aimed to identify the most appropriate antigen candidate for avidity assay, three structural proteins from HIV were used i.e., p24, IDR-gp41 and ID2-Pol employed from the HIV strains circulating in Indonesia. The avidity assay was performed based on ELISA with pH 3 sodium citrate as chaotropic reagent. Serum samples was previously determined as positive and negative reactive by the Indonesian Red Cross. Each sample was tested in triplicates. The results of the avidity index were compared with the corresponding pattern of reactivity shown by Western Blotting. Comparative analysis of the avidity index using the IDR-Gp41 antigen showed correlation with increased value of avidity index with the completeness of the Western Blot reactivity pattern. This finding is not true in antigen ID2-Pol, and p24. Based on the results of the study, it can be concluded that IDR-Gp41 antigen has potential to be used in HIV avidity assay that is based on circulating strains of HIV in Indonesia. AbstrakAIDS merupakan penyakit imunodefisiensi berat yang disebabkan oleh HIV. Penentuan infeksi baru HIV-1 pada level populasi diperlukan guna evaluasi strategi intervensi pencegahan penularan HIV-1. Uji aviditas telah diajukan sebagai salah satu uji deteksi HIV-1. Prinsip uji aviditas adalah kekuatan afinitas epitope antigen HIV terhadap antibodi spesifik yang mengenali epitop tersebut. Ikatan antigen-antibodi yang terbentuk pada fase awal infeksi merupakan ikatan yang lemah dan mudah diputuskan dengan pemberian reagensia chaotropic. Pada fase infeksi lama, ikatan antigen-antibodi yang terbentuk merupakan ikatan yang kuat sehingga tidak mudah diputuskan oleh pemberian reagensia chaotropic. Uji aviditas komersial telah tersedia namun antigen yang digunakan belum tentu sesuai dengan galur HIV yang beredar di Indonesia. Pada penelitian ini digunakan 3 kandidat antigen yaitu p24, IDR-gp41 dan ID2-Pol dari galur HIV yang beredar di Indonesia, untuk menentukan kandidat yang sesuai. Uji aviditas dilakukan dengan prinsip ELISA dengan sodium sitrat pH 3 sebagai reagensia chaotropic. Sampel yang diujikan adalah sampel serum yang telah ditentukan reaktivitasnya sebagai positif dan negatif oleh Palang Merah Indonesia. Sampel diuji secara triplikat. Hasil indeks aviditas sampel dibandingkan dengan pola reaktivitasnya pada uji Western Blot. Analisis perbandingan menunjukkan bahwa peningkatan nilai indeks aviditas yang menggunakan antigen IDR-Gp41 berkorelasi dengan kelengkapan pola reaktivitas uji Western Blot. Hal ini tidak ditemukan pada pengujian menggunakan antigen IDR-Pol2, dan p24. Berdasarkan hasil penelitian, dapat disimpulkan bahwa antigen IDR-Gp41 berpotensi untuk digunakan lebih lanjut dalam pengembangan uji aviditas HIV berbasis galur HIV yang beredar di Indonesia.

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Racine-Brzostek, Sabrina E., Mohsen Karbaschi, Christian Gaebler, P. J. Klasse, Jim Yee, Marina Caskey, He S. Yang et al. "TOP-Plus Is a Versatile Biosensor Platform for Monitoring SARS-CoV-2 Antibody Durability". Clinical Chemistry 67, n. 9 (29 aprile 2021): 1249–58. http://dx.doi.org/10.1093/clinchem/hvab069.

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Abstract Background Low initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody titers dropping to undetectable levels within months after infection have raised concerns about long-term immunity. Both the antibody levels and the avidity of the antibody–antigen interaction should be examined to understand the quality of the antibody response. Methods A testing-on-a-probe “plus” panel (TOP-Plus) was developed to include a newly developed avidity assay built into the previously described SARS-CoV-2 TOP assays that measured total antibody (TAb), surrogate neutralizing antibody (SNAb), IgM, and IgG on a versatile biosensor platform. TAb and SNAb levels were compared with avidity in previously infected individuals at 1.3 and 6.2 months after infection in paired samples from 80 patients with coronavirus disease 2019 (COVID-19). Sera from individuals vaccinated for SARS-CoV-2 were also evaluated for antibody avidity. Results The newly designed avidity assay in this TOP panel correlated well with a reference Bio-Layer Interferometry avidity assay (r = 0.88). The imprecision of the TOP avidity assay was <10%. Although TAb and neutralization activity (by SNAb) decreased between 1.3 and 6.2 months after infection, the antibody avidity increased significantly (P < 0.0001). Antibody avidity in 10 SARS-CoV-2 vaccinated individuals (median: 28 days after vaccination) was comparable to the measured antibody avidity in infected individuals (median: 26 days after infection). Conclusions This highly precise and versatile TOP-Plus panel with the ability to measure SARS-CoV-2 TAb, SNAb, IgG, and IgM antibody levels and avidity of individual sera on one sensor can become a valuable asset in monitoring not only patients infected with SARS-CoV-2 but also the status of individuals’ COVID-19 vaccination response.

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Pereira Arias-Bouda, Lenka M., Sjoukje Kuijper, Anouk Van Der Werf, Lan N. Nguyen, Henk M. Jansen e Arend H. J. Kolk. "Changes in Avidity and Level of Immunoglobulin G Antibodies to Mycobacterium tuberculosis in Sera of Patients Undergoing Treatment for Pulmonary Tuberculosis". Clinical Diagnostic Laboratory Immunology 10, n. 4 (luglio 2003): 702–9. http://dx.doi.org/10.1128/cdli.10.4.702-709.2003.

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ABSTRACT Much is known about specific antibodies and their titers in patients with tuberculosis. However, little is known about the avidity of these antibodies or whether changes in avidity occur during the progression of the disease or during treatment. The aims of this study were to determine the avidity of antibodies to Mycobacterium tuberculosis in patients with pulmonary tuberculosis, to explore the value of avidity determination for the diagnosis of tuberculosis, and to study changes in levels of antibodies and their avidity during treatment. Antibody avidity was measured by an enzyme-linked immunosorbent assay with thiocyanate elution. Avidity indices and serum levels of immunoglobulin G to M. tuberculosis were determined for 22 patients with pulmonary tuberculosis before and during treatment and for 24 patients with other pulmonary diseases. Antibody levels and avidity were both significantly higher in untreated tuberculosis patients than in the controls. Avidity determination had more diagnostic potential than determination of the antibody levels. Tuberculosis patients with a long duration of symptoms had higher antibody avidity than those with a recent onset of symptoms, indicating affinity maturation of specific antibodies during active disease. In the early phase of treatment, a decrease in antibody avidity was observed for 73% of all tuberculosis patients, accompanied by an initial increase in antibody levels in 36% of these patients. These phenomena could be explained by an intense stimulation of the humoral response by antigens released from killed bacteria, reflecting early bactericidal activity of antituberculous drugs leading to the production of low-affinity antibodies against these released antigens.

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Intner, Sara, Michelle Altrich e Niraj Patel. "Comparison of Pneumococcal Avidity and Antibody Concentration in Children with Recurrent Infections: A Retrospective Pilot Study". Journal of Immunological Sciences 4, n. 4 (10 ottobre 2020): 24–30. http://dx.doi.org/10.29245/2578-3009/2020/4.1194.

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Measurement of pneumococcal antibody concentration is a frequently used parameter for functional antibody response to vaccination. Antibody concentration in response to vaccination and strength of antigen-antibody (avidity) interaction are both important measurements of functional antibody response. Both antibody concentration and avidity contribute to immunity against invasive pneumococcal disease. Higher avidity is correlated with increasing bactericidal activity and opsonophagocytosis. On the other hand, patients with lower pneumococcal avidity may be more likely to develop clinically significant pneumococcal sinopulmonary infections. Nine patients with recurrent bacterial respiratory infections were identified by retrospective chart review as having adequate pneumococcal antibody concentrations, but with low avidity for multiple serotypes following immunization with pneumococcal vaccine polyvalent (PPSV23). We assessed response with IgG replacement therapy in these patients. The mean number of serotypes with a normal antibody response (>1.3 mg/ml) among 9 children following immunization with pneumococcal vaccine polyvalent was 19.1 (range 12-22) of 23 serotypes while the mean number of serotypes with a normal avidity response (≥1.0) was 4.7 (range 2-7) of 23 serotypes. Flow cytometry was performed for 8 of the 9 patients prior to starting SCIG replacement therapy. 100% of the cohort experienced a significant decrease in yearly infection rate after starting immunoglobulin replacement. This is the first study to assess the clinical response to immune globulin replacement in patients with normal pneumococcal antibody response but poor pneumococcal avidity, and suggests that patients with poor pneumococcal avidity but apparent normal response by pneumococcal antibody following PPSV23 may benefit from IgG replacement therapy.

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Tiburcio, Monique Gomes Salles, Laís Anversa, Kelly Aparecida Kanunfre, Antonio Walter Ferreira, Virmondes Rodrigues Júnior e Luciana de Almeida Silva. "Anti-Leishmania infantum IgG Antibody Avidity in Visceral Leishmaniasis". Clinical and Vaccine Immunology 20, n. 11 (4 settembre 2013): 1697–702. http://dx.doi.org/10.1128/cvi.00367-13.

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ABSTRACTIgG avidity tests are used to discriminate acute from chronic infections. There are few reports on the IgG avidity profile of patients with visceral leishmaniasis (VL). This study investigated the anti-LeishmaniaIgG avidity in patients with classic VL (n= 10), patients showing clinical cure after treatment (n= 18), and asymptomatic subjects with at least one positiveLeishmaniatest (n= 20). All subjects were from areas in Brazil where VL is endemic. Serum samples were collected from each subject on two different occasions. IgG avidity was evaluated by Western blotting. The proportion of high-avidity antibodies was higher in all samples from patients with classic VL. In contrast, low-avidity antibodies predominated in subjects with a history of VL, including 13 cases (72.2%) in the first assessment and 14 (77.8%) in the second. Fifteen (75%) of the asymptomatic subjects presented a predominance of low-avidity antibodies in the first assessment, and the frequency of high-avidity antibodies increased over time in seven subjects (35%) of this group. Antibodies against the 14- and/or 16-kDa antigen fraction were detected in the first assessment in all patients with classic VL, in 10 (55.5%) treated patients, and in 10 (50%) asymptomatic subjects. These were high-avidity antibodies in most cases. In the asymptomatic group, an increase in IgG avidity against the 14- and/or 16-kDa antigen fraction was observed in three cases (15%). The results indicate distinct responses in infected and asymptomatic subjects, probably associated with the length of time after infection. In this respect, IgG avidity tests represent a new approach to better characterize asymptomatic VL.

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Marcipar, Iván S., Marikena G. Risso, Ariel M. Silber, Silvia Revelli e Alberto J. Marcipar. "Antibody Maturation in Trypanosoma cruzi-Infected Rats". Clinical Diagnostic Laboratory Immunology 8, n. 4 (1 luglio 2001): 802–5. http://dx.doi.org/10.1128/cdli.8.4.802-805.2001.

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ABSTRACT The study of antibody avidity changes during infection has improved the understanding of the pathologic processes involved in several infectious diseases. In some infections, like toxoplasmosis, this information is being used for diagnostic purposes. Results of the evolution of antibody avidity for different specific antigens inTrypanosome cruzi-infected rats are presented. A Western blotting technique, combined with avidity analysis to identify antigens that elicit high-avidity antibodies, is suggested. In this system, antibodies showed high avidity values only during the chronic phase of infection and only in relation to antibodies against 21-, 33-, 41-, 42-, 56-, 58-, 66-, and 72-kDa antigens. Finally, a 97-kDa T. cruzi antigen, which was recognized by high-avidity antibodies and occurred in noninfected rats, was identified. These results allow us to evaluate the different antigens in chagasic infection. Our results show that with the correct choice of antigen it is possible to detect differences in maturation of antibodies and to discriminate, in an experimental model, between recent (acute) and chronic infections.

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Alex, Diviya, Tennison Inba Raj Williams, Jaiprasath Sachithanandham, Swaminathan Prasannakumar, John Paul Demosthenes, Veena Vadhini Ramalingam, Punitha John Victor, Priscilla Rupali, Gnanadurai John Fletcher e Rajesh Kannangai. "Performance of a Modified In-House HIV-1 Avidity Assay among a Cohort of Newly Diagnosed HIV-1 Infected Individuals and the Effect of ART on the Maturation of HIV-1 Specific Antibodies". Current HIV Research 17, n. 2 (2 settembre 2019): 134–45. http://dx.doi.org/10.2174/1570162x17666190712125606.

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Background: Viral kinetics impact humoral immune response to HIV; antibody avidity testing helps distinguish recent (<6 months) and long-term HIV infection. This study aims to determine the frequency of recent HIV-1 infection among clients attending ICTC (Integrated Counselling and Testing Centre) using a commercial EIA, to correlate it with a modified in-house avidity assay and to study the impact of ART on anti-HIV-1 antibody maturation. Method: Commercial LAg Avidity EIA was used to detect antibody avidity among 117 treatment naïve HIV-1 infected individuals. A second-generation HIV ELISA was modified for in-house antibody avidity testing and cutoff was set based on Receiver Operating Characteristic (ROC) analysis. Archived paired samples from 25 HIV-1 infected individuals before ART and after successful ART; samples from 7 individuals responding to ART and during virological failure were also tested by LAg Avidity EIA. Results: Six individuals (5.1%) were identified as recently infected by a combination of LAg avidity assay and HIV-1 viral load testing. The modified in-house avidity assay demonstrated sensitivity and specificity of 100% and 98.2%, respectively, at AI=0.69 by ROC analysis. Median ODn values of individuals when responding to ART were significantly lower than pre-ART [4.136 (IQR 3.437– 4.827) vs 4.455 (IQR 3.748–5.120), p=0.006] whereas ODn values were higher during virological failure [4.260 (IQR 3.665 – 4.515) vs 2.868 (IQR 2.247 – 3.921), p=0.16]. Conclusion: This modified in-house antibody avidity assay is an inexpensive method to detect recent HIV-1 infection. ART demonstrated significant effect on HIV-1 antibody avidity owing to changes in viral kinetics.

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Yoshida, Márcia, Maria Carmen Arroyo Sanchez e Maria Aparecida Shikanai-Yasuda. "Increased Immunoglobulin G Anti-Paracoccidioides brasiliensis Serum Antibody Avidity as a Predictor of Favorable Posttherapeutic Evolution in Paracoccidioidomycosis". Clinical and Vaccine Immunology 16, n. 11 (2 settembre 2009): 1583–86. http://dx.doi.org/10.1128/cvi.00265-09.

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ABSTRACT Paracoccidioidomycosis is endemic in Latin America, and ca. 80% of all cases occur in Brazil. Little is known about antibody avidity or the evolution of such avidity in the posttherapeutic period for the different clinical presentations of the disease. In the present study, we evaluated 53 patients with paracoccidioidomycosis and calculated the avidity index. Medium- and high-avidity antibodies were found in 79.5% of patients with chronic presentation (n = 39). Among patients with the acute form (n = 14), 57.1% of the antibodies presented low avidity. In the posttherapeutic period, there was a significant increase in antibody avidity in patients presenting with the chronic multifocal form. In our preliminary study, which needs to be confirmed using a larger number of samples, the optimized method for studying antibody avidity detected differences among the clinical presentations of the mycosis and indicated the value of the avidity index as a marker of posttherapeutic evolution of patients with a multifocal chronic form of the disease.

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Chan, K. H., K. Sonnenberg, M. Niedrig, S. Y. Lam, C. M. Pang, K. M. Chan, S. K. Ma, W. H. Seto e J. S. M. Peiris. "Use of Antibody Avidity Assays for Diagnosis of Severe Acute Respiratory Syndrome Coronavirus Infection". Clinical and Vaccine Immunology 14, n. 11 (19 settembre 2007): 1433–36. http://dx.doi.org/10.1128/cvi.00056-07.

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ABSTRACT An indirect immunofluorescent assay (Euroimmun AG, Luebeck, Germany) was used to investigate the avidity of immunoglobulin G (IgG), IgM, IgA, and total Ig (IgGAM) antibody responses to severe acute respiratory syndrome coronavirus (SARS CoV) infections. Serial serum samples from eight patients collected during the first, third, and ninth months after the onset of infection were evaluated. It was found that low-avidity IgG antibodies were detected in 15/15 (100%), 1/5 (20%), and 0/8 (0%) serum samples collected during the first, third, and ninth months after the onset of symptoms, respectively. Low-avidity antibodies of IgA and IgM subclasses were detected in 14/14 (100%) and 3/14 (21%) serum samples, respectively, collected in the first month after the onset of infection. However, IgA antibodies remained low in avidity in a proportion of patients even during late convalescence. As a consequence, IgG antibody avidity assays gave better discrimination between acute-phase and late-convalescent-phase serum samples than IgM, IgA, or IgGAM assays. In two of these patients, sequential serum samples were also tested for IgG avidity against human CoV strains OC43 and 229E in parallel. While SARS CoV infections induced an anamnestic IgG antibody response to the 229E and OC43 viruses, these cross-reactive antibodies remained of high avidity from early (the first month) postinfection. The results showed that assays to detect low-avidity antibody may be useful for discriminating early from late antibody responses and also for distinguishing anamnestic cross-reactive antibody responses from primary specific responses. This may be useful in some clinical situations.

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Griswold, William R. "A Quantitative Relationship Between Antibody Affinity and Antibody Avidity". Immunological Investigations 16, n. 2 (gennaio 1987): 97–106. http://dx.doi.org/10.3109/08820138709030567.

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Welten, Suzanne P. M., Anke Redeker, René E. M. Toes e Ramon Arens. "Viral Persistence Induces Antibody Inflation without Altering Antibody Avidity". Journal of Virology 90, n. 9 (17 febbraio 2016): 4402–11. http://dx.doi.org/10.1128/jvi.03177-15.

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ABSTRACTAntibodies are implicated in long-term immunity against numerous pathogens, and because of this property, antibody induction is the basis for many vaccines. Little is known about the influence of viral persistence on the evolving antibody response. Here, we examined the characteristics of antibody responses to persistent infection by employing the prototypic betaherpesvirus family member cytomegalovirus (CMV) in experimental mouse models. During the course of infection, mouse CMV (MCMV)-specific IgM and IgG responses are elicited; however, IgG levels gradually inflate in the persistent phase of infection while IgM levels are stably maintained. Whereas CD27-CD70 interactions are dispensable, the CD28/B7 costimulatory pathway is critical for the class switching of MCMV-specific IgM-to-IgG B cell responses, which corresponds to the CD28/B7-dependent formation of CD4+T follicular helper cells (TFH) and germinal center (GC) B cells. Furthermore, the initial viral inoculum dose dictates the height of the antibody levels during IgG antibody inflation and relates to the induction of long-lived plasma cells and memory B cells. Antibody avidity nonetheless is not altered after the establishment of viral persistence and occurs independently of the inoculum doses. However, repetitive challenge with intact viral particles, accompanied by increased GC reactivity, promotes the development of high-avidity IgG responses with neutralizing capacity. These insights can be used for the rational design of CMV-based vaccines aimed at inducing antibody responses.IMPORTANCEAntibodies provide long-term protection to different pathogens. However, how antibody responses develop during persistent virus infection is not entirely clear. Here, we characterize factors that influence the virus-specific antibody response to persistent CMV. This study describes that during persistent infection, CMV-specific IgM antibody levels are stably maintained while IgG2b and IgG2c levels gradually inflate over time. In contrast, the IgG avidity remains similar after the establishment of viral persistence. The induction of T follicular helper cells and GC B cells requires CD4+T cell help and CD28/B7 costimulation signals and is essential for the development of CMV-specific IgG antibody responses. Furthermore, neutralizing CMV-specific antibodies appear to develop late after infection, yet the neutralizing capacity can be improved upon repetitive viral challenge that is associated with increased GC reactivity. The results described here could inform the use of CMV-based vaccines and may help to understand how our immune system copes with this persistent virus.

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Usinger, William R., e Alexander H. Lucas. "Avidity as a Determinant of the Protective Efficacy of Human Antibodies to Pneumococcal Capsular Polysaccharides". Infection and Immunity 67, n. 5 (1 maggio 1999): 2366–70. http://dx.doi.org/10.1128/iai.67.5.2366-2370.1999.

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ABSTRACT Antibodies reactive with capsular polysaccharides are considered the principal mediators of immunity against invasive diseases caused byStreptococcus pneumoniae. In this study, we tested the hypothesis that anti-pneumococcal capsular polysaccharide (PPS) antibody avidity can influence protective efficacy. We measured the avidities of individual adult postvaccination immunoglobulin G2 (IgG2) antibodies to PPS serotypes 6B and 23F and examined the relationship between avidity and opsonophagocytic and mouse-protective activities. The avidities of PPS 6B- and PPS 23F-specific IgG2 antibodies ranged from 6 to 31 nM−1 and from 3 to 20 nM−1, respectively. We observed an inverse correlation between the magnitude of avidity and the amount of antibody required to protect mice against lethal bacteremia caused by serotype 6B pneumococci. Similarly, higher-avidity antibodies were more effective than lower-avidity antibodies in vitro in mediating complement-dependent opsonophagocytosis of both 6B and 23F pneumococci. These data suggest that in adults, PPS antibodies are sufficiently polymorphic to possess biologically significant variations in avidity. We conclude that avidity functions as an important determinant of anticapsular antibody protective efficacy against pneumococci.

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Benner, Sarah E., Eshan U. Patel, Oliver Laeyendecker, Andrew Pekosz, Kirsten Littlefield, Yolanda Eby, Reinaldo E. Fernandez et al. "SARS-CoV-2 Antibody Avidity Responses in COVID-19 Patients and Convalescent Plasma Donors". Journal of Infectious Diseases 222, n. 12 (10 settembre 2020): 1974–84. http://dx.doi.org/10.1093/infdis/jiaa581.

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Abstract Background Convalescent plasma therapy is a leading treatment for conferring temporary immunity to COVID-19–susceptible individuals or for use as post-exposure prophylaxis. However, not all recovered patients develop adequate antibody titers for donation and the relationship between avidity and neutralizing titers is currently not well understood. Methods SARS-CoV-2 anti-spike and anti-nucleocapsid IgG titers and avidity were measured in a longitudinal cohort of COVID-19 hospitalized patients (n = 16 individuals) and a cross-sectional sample of convalescent plasma donors (n = 130). Epidemiologic correlates of avidity were examined in donors by linear regression. The association of avidity and a high neutralizing titer (NT) were also assessed in donors using modified Poisson regression. Results Antibody avidity increased over duration of infection and remained elevated. In convalescent plasma donors, higher levels of anti-spike avidity were associated with older age, male sex, and hospitalization. Higher NTs had a stronger positive correlation with anti-spike IgG avidity (Spearman ρ = 0.386; P < .001) than with anti-nucleocapsid IgG avidity (Spearman ρ = 0.211; P = .026). Increasing levels of anti-spike IgG avidity were associated with high NT (≥160) (adjusted prevalence ratio = 1.58 [95% confidence interval = 1.19–2.12]), independent of age, sex, and hospitalization. Conclusions SARS-CoV-2 antibody avidity correlated with duration of infection and higher neutralizing titers, suggesting a potential alternative screening parameter for identifying optimal convalescent plasma donors.

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Leite, Marcel, Sonia Siciliano, Lucia Silvieri A. Rocha, Teresa R. Justa, Katia Regina César e Celso F. H. Granato. "Correlation between specific IgM levels and percentage IgG-class antibody avidity to Toxoplasma gondii". Revista do Instituto de Medicina Tropical de São Paulo 50, n. 4 (agosto 2008): 237–42. http://dx.doi.org/10.1590/s0036-46652008000400010.

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Toxoplasmosis is an usually asymptomatic worldwide disseminated infection. In its congenital presentation it may lead to abortion or fetal malformations. Antenatal evaluation is considered of paramount importance to identify seronegative women and allow for prophylaxis. Recent improvements in sensitivity of IgM tests has made IgM detection an extremely protracted acute phase marker, and IgG avidity evaluation test became necessary. Observation has shown that a correlation can be established between IgM levels and avidity percentages, suggesting that frequently the avidity test may not be necessary. In this study we analyzed Toxoplasma gondii IgM levels of 202 samples and their IgG avidity percentages, in order to define specific levels whose IgM quantification could by itself define serodiagnosis and therefore make the avidity evaluation unnecessary. We showed that for IgM levels bellow 2.0 and above 6.0 serodiagnosis of toxoplasmosis could be established without need of IgG avidity test. IgM levels between these two parameters are associated with varying avidity indexes highlighting the importance of its evaluation as a means to confirm toxoplasmosis. Following this demonstration it was possible to avoid the avidity test for 75% of the cases, to reduce the turnaround time and to reduce costs.

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Alexander, Marina R., Rajesh Ringe, Rogier W. Sanders, James E. Voss, John P. Moore e Per Johan Klasse. "What Do Chaotrope-Based Avidity Assays for Antibodies to HIV-1 Envelope Glycoproteins Measure?" Journal of Virology 89, n. 11 (25 marzo 2015): 5981–95. http://dx.doi.org/10.1128/jvi.00320-15.

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ABSTRACTWhen HIV-1 vaccine candidates that include soluble envelope glycoproteins (Env) are tested in humans and other species, the resulting antibody responses to Env are sifted for correlates of protection or risk. One frequently used assay measures the reduction in antibody binding to Env antigens by an added chaotrope (such as thiocyanate). Based on that assay, an avidity index was devised for assessing the affinity maturation of antibodies of unknown concentration in polyclonal sera. Since a high avidity index was linked to protection in animal models of HIV-1 infection, it has become a criterion for evaluating antibody responses to vaccine candidates. But what does the assay measure and what does an avidity index mean? Here, we have used a panel of monoclonal antibodies to well-defined epitopes on Env (gp120, gp41, and SOSIP.664 trimers) to explore how the chaotrope acts. We conclude that the chaotrope sensitivity of antibody binding to Env depends on several properties of the epitopes (continuity versus tertiary- and quaternary-structural dependence) and that the avidity index has no simple relationship to antibody affinity for functional Env spikes on virions. We show that the binding of broadly neutralizing antibodies against quaternary-structural epitopes is particularly sensitive to chaotrope treatment, whereas antibody binding to epitopes in variable loops and to nonneutralization epitopes in gp41 is generally resistant. As a result of such biases, the avidity index may at best be a mere surrogate for undefined antibody or other immune responses that correlate weakly with protection.IMPORTANCEAn effective HIV-1 vaccine is an important goal. Such a vaccine will probably need to induce antibodies that neutralize typically transmitted variants of HIV-1, preventing them from infecting target cells. Vaccine candidates have so far failed to induce such antibody responses, although some do protect weakly against infection in animals and, possibly, humans. In the search for responses associated with protection, an avidity assay based on chemical disruption is often used to measure the strength of antibody binding. We have analyzed this assay mechanistically and found that the epitope specificity of an antibody has a greater influence on the outcome than does its affinity. As a result, the avidity assay is biased toward the detection of some antibody specificities while disfavoring others. We conclude that the assay may yield merely indirect correlations with weak protection, specifically when Env vaccination has failed to induce broad neutralizing responses.

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FENOY, S., M. RODERO, E. PONS, C. AGUILA e C. CUÉLLAR. "Follow-up of antibody avidity in BALB/c mice infected withToxocara canis". Parasitology 135, n. 6 (16 aprile 2008): 725–33. http://dx.doi.org/10.1017/s0031182008004368.

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SUMMARYIn humanToxocara canisinfection, an association has been shown between high IgG avidity in the chronic phase and low IgG avidity in recently acquired toxocarosis. The evolution of the antibody response in terms of avidity has been carried out through aT. canisinfection in BALB/c mice. Infection withT. canisembryonated eggs (EE) was carried out with single doses (SD) of 6, 12, 50, 100, 200 or 1000 EE/mouse and with multiple doses (MD) of 200 and 1000 EE. Specific antibodies againstT. canis(IgM+G, IgG, IgG1 and IgM) were detected by ELISA and Western Blot (WB) techniques in the presence and absence of urea. With the ELISA method, an increase in the avidity index (AI) of around 50% was detected from days 40–80 p.i. to the end of the study, with all the doses studied. The WB method showed the presence of high avidity antibodies bound to 100 kDa and 75 kDaT. canisproteins in all the cases when the IgM+G and the IgG1 antibodies were investigated. Antibodies of variable avidity were observed in those sera that recognized the group of low molecular weight proteins, between 37 kDa and 25 kDa.

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Velander, William H., Rapti D. Madurawe, Anuradha Subramanian, Guneet Kumar, Gurudas Sinai-Zingde, Judy S. Riffle e Carolyn L. Orthner. "Polyoxazoline-Peptide adducts that retain antibody avidity". Biotechnology and Bioengineering 39, n. 10 (25 aprile 1992): 1024–30. http://dx.doi.org/10.1002/bit.260391006.

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Kangro, Hillar O., Shazad Manzoor e David R. Harper. "Antibody avidity following varicella-zoster virus infections". Journal of Medical Virology 33, n. 2 (febbraio 1991): 100–105. http://dx.doi.org/10.1002/jmv.1890330207.

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19

Schoub, Barry D., Nigel K. Blackburn, Sylvia Johnson, Jo M. McAnerney e Bennie Miller. "Low antibody avidity in elderly chickenpox patients". Journal of Medical Virology 37, n. 2 (giugno 1992): 113–15. http://dx.doi.org/10.1002/jmv.1890370207.

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20

O'DELL, D. S., e J. L. EBERSOLE. "Avidity of antibody responses toActinobacillus actinomycetemcomitansin periodontitis". Clinical & Experimental Immunology 101, n. 2 (agosto 1995): 295–301. http://dx.doi.org/10.1111/j.1365-2249.1995.tb08354.x.

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21

Harris, Shannon L., How Tsao, Lindsey Ashton, David Goldblatt e Philip Fernsten. "Avidity of the Immunoglobulin G Response to a Neisseria meningitidis Group C Polysaccharide Conjugate Vaccine as Measured by Inhibition and Chaotropic Enzyme-Linked Immunosorbent Assays". Clinical and Vaccine Immunology 14, n. 4 (7 febbraio 2007): 397–403. http://dx.doi.org/10.1128/cvi.00241-06.

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Abstract (sommario):

ABSTRACT Antibody avidity, the strength of the multivalent interaction between antibodies and their antigens, is an important characteristic of protective immune responses. We have developed an inhibition enzyme-linked immunosorbent assay (ELISA) to measure antibody avidity for the capsular polysaccharide (PS) of Neisseria meningitidis group C (MnC) and determined the avidity constants (KD s) for 100 sera from children immunized with an MnC PS conjugate vaccine. The avidity constants were compared to the avidity indices (AI) obtained for the same sera using a chaotropic ELISA protocol. After the primary immunization series, the geometric mean (GM) KD was 674 nM and did not change in the months following immunization. However, the GM avidity did increase after the booster dose (GM KD , 414 nM 1 month after booster immunization). In contrast, the GM AI increased from an initial value of 118 after the primary immunization series to 147 6 months after the completion of the primary immunization series and then further increased to 178 after booster immunization. At the individual subject level, the avidity constant and AI correlated after the primary immunization series and after booster immunization but not prior to boosting. This work suggests that the AI, as measured by the chaotropic ELISA, in contrast to the KD , reflects changes that render antibody populations less susceptible to disruption by chaotropic agents without directly affecting the strength of the binding interactions.

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22

Dollard, Sheila C., Stephanie A. S. Staras, Minal M. Amin, D. Scott Schmid e Michael J. Cannon. "National Prevalence Estimates for Cytomegalovirus IgM and IgG Avidity and Association between High IgM Antibody Titer and Low IgG Avidity". Clinical and Vaccine Immunology 18, n. 11 (14 settembre 2011): 1895–99. http://dx.doi.org/10.1128/cvi.05228-11.

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ABSTRACTPrimary cytomegalovirus (CMV) infection of the mother during pregnancy presents risk of CMV infection of the fetus with resulting permanent disability. CMV IgM antibody is generated following primary CMV infection but also can appear during nonprimary CMV infection and is thus of limited diagnostic use by itself. In contrast, the presence of low CMV IgG avidity has been shown to be a unique and reliable serologic indicator of primary CMV infection. We measured CMV IgG and IgM antibody levels and IgG avidity in sera from a population sample of 6,067 U.S. women aged 12 to 49 years from NHANES (National Health and Nutrition Examination Survey). The CMV IgG prevalence was 58% overall and increased strongly with age. The CMV IgM prevalence was 3.0% overall and remained relatively flat across age groups. The prevalence of low IgG avidity was 2.0% overall, decreased sharply with age, and was seen mainly among IgM-positive sera. Fourteen to 18% of the CMV IgM-positive sera were low IgG avidity, presumably representing primary CMV infection. High CMV IgM antibody titer was a strong predictor of low IgG avidity. The ability to reliably identify primary CMV infection during pregnancy is important for management of the pregnancy, including possible treatment options for the fetus. Both IgM and IgG avidity measurements provide useful clinical information for evaluating primary CMV infection, although commercial tests for CMV IgG avidity are not yet widely available in the United States.

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23

Holliman, R. E., R. Raymond, N. Renton e J. D. Johnson. "The diagnosis of toxoplasmosis using IgG avidity". Epidemiology and Infection 112, n. 2 (aprile 1994): 399–408. http://dx.doi.org/10.1017/s0950268800057812.

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SUMMARYCurrent methods to establish the duration of toxoplasma infection in pregnant women and for the diagnosis of toxoplasmosis in the neonate or HIV infected patient have significant limitations. We assessed the precision of a commercial ELISA for the detection of toxoplasma specific IgG and adapted the assay to measure avidity using an elution agent washing step. The sensitivity and specificity of the ELISA were 100 and 75 % respectively and optimal measurement of avidity was achieved using 6 M urea as the elution agent.Toxoplasma lymphadenopathy of less than 3 months duration was associated with low avidity specific IgG but some discordant findings were recorded. Serial measurement of IgG avidity assisted the distinction between actively produced antibody in infants with congenital toxoplasmosis and passively acquired antibody of maternal origin in uninfected babies. There was no significant difference between avidity levels in HIV infected patients with or without cerebral toxoplasmosis.

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24

Marcolino, P. T., D. A. O. Silva, P. G. Leser, M. E. Camargo e J. R. Mineo. "Molecular Markers in Acute and Chronic Phases of Human Toxoplasmosis: Determination of Immunoglobulin G Avidity by Western Blotting". Clinical Diagnostic Laboratory Immunology 7, n. 3 (1 maggio 2000): 384–89. http://dx.doi.org/10.1128/cdli.7.3.384-389.2000.

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Abstract (sommario):

ABSTRACT We characterized antigenic markers recognized by human serum samples from patients presenting with acute and chronic toxoplasmosis by the determination of immunoglobulin G (IgG) antibody avidity by a Western blot modified technique (avidity immunoblotting) that includes the dissociation of the antigen-antibody interaction with 6 or 8 M urea solutions. Human serum samples from 20 patients presenting with recent infection and from 20 patients with chronic infection were analyzed. It was observed that bands p16, p32, p38, p40, p43, p54, p60, p66, and p97 were more frequently recognized by low-avidity IgG in recent infection and by high-avidity IgG in chronic toxoplasmosis. From these antigenic bands, p38 can be characterized as an optimal antigenic marker of low avidity for recent forms of toxoplasmosis due to a significant decrease of their frequencies (from 80 to 0%) after treatment with 6 M urea solutions. The p30 antigen was not considered a good marker to distinguish acute from chronic infection since corresponding IgG antibodies were determined to have high avidity in both phases of the infection. Thus, the avidity immunoblotting assay proved to be a useful tool for determining antigenic markers of recent and chronic phases ofToxoplasma gondii infection.

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25

Romero-Steiner, Sandra, Patricia F. Holder, Patricia Gomez de Leon, Willie Spear, Thomas W. Hennessy e George M. Carlone. "Avidity Determinations for Haemophilus influenzae Type b Anti-Polyribosylribitol Phosphate Antibodies". Clinical Diagnostic Laboratory Immunology 12, n. 9 (settembre 2005): 1029–35. http://dx.doi.org/10.1128/cdli.12.9.1029-1035.2005.

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ABSTRACT Determination of antibody avidity measurements can be difficult in human serum depending on the population evaluated. We evaluated three approaches for the determination of antibody avidity for immunoglobulin G (IgG). These approaches were (i) elution of bound antibody with increasing concentrations of a chaotropic agent using a single serum dilution, (ii) binding interference of multiple serum dilutions by a single concentration of a chaotrope, and (iii) elution of multiple serum dilutions by a single concentration of a chaotrope. Parameters that affect the determination of avidity measurements and their limitations were evaluated with pre- and post-Haemophilus influenzae type b conjugate vaccination sera (n = 89). We determined that elution of low-avidity antibodies present in multiple dilutions of the serum sample by a single concentration of a chaotrope (0.15 M sodium thiocyanate [NaSCN]) was optimal for the determination of avidity measurements throughout a wide range of IgG concentrations (0.94 to 304.6 μg/ml). The percent reduction in concentration as determined by the elution assay with 0.15 M NaSCN correlated highly (r = 0.84) with weighted averages obtained by an elution assay with multiple solutions of NaSCN. The correlation (r = 0.57) between elution and binding interference, when a single concentration of a chaotrope was used, was lower than the correlation between the two elution methods (r = 0.84). We found that the serum dilution, the heterogeneity of the antibody population, and the concentration of the chaotrope were the primary variables affecting avidity determinations. In this study, we present multiple analysis methods depending on the methodology used. We also present the factors that affect the analysis of avidity determinations given the polyclonal nature of human sera. This experimental approach should benefit the evaluation of similar antibodies induced by other bacterial polysaccharide vaccines.

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26

Richmond, J. F. L., S. Lu, J. C. Santoro, J. Weng, Shiu-Lok Hu, D. C. Montefiori e H. L. Robinson. "Studies of the Neutralizing Activity and Avidity of Anti-Human Immunodeficiency Virus Type 1 Env Antibody Elicited by DNA Priming and Protein Boosting". Journal of Virology 72, n. 11 (1 novembre 1998): 9092–100. http://dx.doi.org/10.1128/jvi.72.11.9092-9100.1998.

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Abstract (sommario):

ABSTRACT DNA vaccination is an effective means of eliciting strong antibody responses to a number of viral antigens. However, DNA immunization alone has not generated persistent, high-titer antibody and neutralizing antibody responses to human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env). We have previously reported that DNA-primed anti-Env antibody responses can be augmented by boosting with Env-expressing recombinant vaccinia viruses. We report here that recombinant Env protein provides a more effective boost of DNA-initiated antibody responses. In rabbits primed with Env-expressing plasmids, protein boosting increased titer, persistence, neutralizing activity, and avidity of anti-Env responses. While titers increased rapidly after boosting, avidity and neutralizing activity matured more slowly over a 6-month period following protein boosting. DNA priming and protein immunization with HIV-1 HXB-2 Env elicited neutralizing antibody for T cell line-adapted, but not primary isolate, viruses. The most effective neutralizing antibody responses were observed after priming with plasmids which expressed noninfectious virus-like particles. In contrast to immunizations with HIV-1 Env, DNA immunizations with the influenza virus hemagglutinin glycoprotein did not require a protein boost to achieve high-titer antibody with good avidity and persistence.

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27

Ekström, Nina, Heidi Åhman, Arto Palmu, Sinikka Grönholm, Terhi Kilpi e Helena Käyhty. "Concentration and High Avidity of Pneumococcal Antibodies Persist at Least 4 Years after Immunization with Pneumococcal Conjugate Vaccine in Infancy". Clinical and Vaccine Immunology 20, n. 7 (8 maggio 2013): 1034–40. http://dx.doi.org/10.1128/cvi.00039-13.

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ABSTRACTTo provide more extensive evidence of long-term effects of vaccination on immunity againstStreptococcus pneumoniae, a follow-up study of the Finnish Otitis Media (FinOM) Vaccine Trial was conducted. One of the objectives was to assess the persistence and avidity of pneumococcal antibodies 4 years after pneumococcal vaccination given in infancy. Children with complete follow-up in the FinOM trial up to 24 months of age were invited to a single visit in their fifth year of life. A blood sample was taken from all children for determination of anticapsular antibody concentrations to vaccine serotypes and avidity of antibodies to three serotypes. Children had been vaccinated at 2, 4, 6, and 12 months of age with 7-valent pneumococcal capsular polysaccharide, CRM197 conjugate vaccine (PCV7), or a control vaccine. Serum IgG antibody concentrations to vaccine serotypes remained significantly higher in children who had received PCV7 than in control children for 4 years after the fourth PCV7 dose. Concentrations of antibodies to frequently carried serotypes (6B and 19F) declined less than those of antibodies to a rarely carried serotype (4), suggesting that natural boosting contributed to antibody persistence. Furthermore, antibody avidity was significantly higher in PCV7 than control vaccine recipients. Four doses of PCV7 given in infancy elicit long-lasting antibody responses with high avidity. (This study has been registered at ClinicalTrials.gov under registration no. NCT00378417.)

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28

Alam, Mohammad Murshid, Mohammad Arifuzzaman, Shaikh Meshbahuddin Ahmad, M. Ismail Hosen, Mohammad Arif Rahman, Rasheduzzaman Rashu, Alaullah Sheikh, Edward T. Ryan, Stephen B. Calderwood e Firdausi Qadri. "Study of Avidity of Antigen-Specific Antibody as a Means of Understanding Development of Long-Term Immunological Memory after Vibrio cholerae O1 Infection". Clinical and Vaccine Immunology 20, n. 1 (31 ottobre 2012): 17–23. http://dx.doi.org/10.1128/cvi.00521-12.

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Abstract (sommario):

ABSTRACTThe avidity of antibodies to specific antigens and the relationship of avidity to memory B cell responses to these antigens have not been studied in patients with cholera or those receiving oral cholera vaccines. We measured the avidity of antibodies to cholera toxin B subunit (CTB) andVibrio choleraeO1 lipopolysaccharide (LPS) in Bangladeshi adult cholera patients (n= 30), as well as vaccinees (n= 30) after administration of two doses of a killed oral cholera vaccine. We assessed antibody and memory B cell responses at the acute stage in patients or prior to vaccination in vaccinees and then in follow-up over a year. Both patients and vaccinees mounted CTB-specific IgG and IgA antibodies of high avidity. Patients showed longer persistence of these antibodies than vaccinees, with persistence lasting in patients up to day 270 to 360. The avidity of LPS-specific IgG and IgA antibodies in patients remained elevated up to 180 days of follow-up. Vaccinees mounted highly avid LPS-specific antibodies at day 17 (3 days after the second dose of vaccine), but the avidity waned rapidly to baseline by 30 days. We examined the correlation between antigen-specific memory B cell responses and avidity indices for both antigens. We found that numbers of CTB- and LPS-specific memory B cells significantly correlated with the avidity indices of the corresponding antibodies (P< 0.05; Spearman'sρ= 0.28 to 0.45). These findings suggest that antibody avidity after infection and immunization is a good correlate of the development and maintenance of memory B cell responses toVibrio choleraeO1 antigens.

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29

Zhu, Xuekai, Lei Wang, Rongzhi Liu, Barry Flutter, Shenghua Li, Jie Ding, Hua Tao, Changzhen Liu, Meiyi Sun e Bin Gao. "COMBODY: one‐domain antibody multimer with improved avidity". Immunology & Cell Biology 88, n. 6 (9 marzo 2010): 667–75. http://dx.doi.org/10.1038/icb.2010.21.

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30

Perciani, C. T., P. S. Peixoto, W. O. Dias, F. S. Kubrusly e M. M. Tanizaki. "Improved method to calculate the antibody avidity index". Journal of Clinical Laboratory Analysis 21, n. 3 (2007): 201–6. http://dx.doi.org/10.1002/jcla.20172.

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31

Rudnick, Stephen I., e Gregory P. Adams. "Affinity and Avidity in Antibody-Based Tumor Targeting". Cancer Biotherapy and Radiopharmaceuticals 24, n. 2 (aprile 2009): 155–61. http://dx.doi.org/10.1089/cbr.2009.0627.

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32

Pullen, G. R., Margaret G. Fitzgerald e C. S. Hosking. "Antibody avidity determination by ELISA using thiocyanate elution". Journal of Immunological Methods 86, n. 1 (gennaio 1986): 83–87. http://dx.doi.org/10.1016/0022-1759(86)90268-1.

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33

Alam, Mohammad Murshid, Daniel T. Leung, Marjahan Akhtar, Mohammad Nazim, Sarmin Akter, Taher Uddin, Farhana Khanam et al. "Antibody Avidity in Humoral Immune Responses in Bangladeshi Children and Adults following Administration of an Oral Killed Cholera Vaccine". Clinical and Vaccine Immunology 20, n. 10 (7 agosto 2013): 1541–48. http://dx.doi.org/10.1128/cvi.00341-13.

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Abstract (sommario):

ABSTRACTAntibody avidity for antigens following disease or vaccination increases with affinity maturation and somatic hypermutation. In this study, we followed children and adults in Bangladesh for 1 year following oral cholera vaccination and measured the avidity of antibodies to the T cell-dependent antigen cholera toxin B subunit (CTB) and the T cell-independent antigen lipopolysaccharide (LPS) in comparison with responses in other immunological measurements. Children produced CTB-specific IgG and IgA antibodies of high avidity following vaccination, which persisted for several months; the magnitudes of responses were comparable to those seen in adult vaccinees. The avidity of LPS-specific IgG and IgA antibodies in vaccinees increased significantly shortly after the second dose of vaccine but waned rapidly to baseline levels thereafter. CTB-specific memory B cells were present for only a short time following vaccination, and we did not find significant memory B cell responses to LPS in any age group. For older children, there was a significant correlation between CTB-specific memory T cell responses after the second dose of vaccine and CTB-specific IgG antibody avidity indices over the subsequent year. These findings suggest that vaccination induces a longer-lasting increase in the avidity of antibodies to a T cell-dependent antigen than is measured by a memory B cell response to that antigen and that early memory T cell responses correlate well with the subsequent development of higher-avidity antibodies.

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34

Cuda, Tahleesa J., Yaowu He, Thomas Kryza, Tashbib Khan, Brian W. Tse, Kamil A. Sokolowski, Cheng Liu et al. "Preclinical Molecular PET-CT Imaging Targeting CDCP1 in Colorectal Cancer". Contrast Media & Molecular Imaging 2021 (13 settembre 2021): 1–12. http://dx.doi.org/10.1155/2021/3153278.

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Abstract (sommario):

Colorectal cancer (CRC) is the third most common malignancy in the world, with 22% of patients presenting with metastatic disease and a further 50% destined to develop metastasis. Molecular imaging uses antigen-specific ligands conjugated to radionuclides to detect and characterise primary cancer and metastases. Expression of the cell surface protein CDCP1 is increased in CRC, and here we sought to assess whether it is a suitable molecular imaging target for the detection of this cancer. CDCP1 expression was assessed in CRC cell lines and a patient-derived xenograft to identify models suitable for evaluation of radio-labelled 10D7, a CDCP1-targeted, high-affinity monoclonal antibody, for preclinical molecular imaging. Positron emission tomography-computed tomography was used to compare zirconium-89 (89Zr)-10D7 avidity to a nonspecific, isotype control 89Zr-labelled IgGκ1 antibody. The specificity of CDCP1-avidity was further confirmed using CDCP1 silencing and blocking models. Our data indicate high avidity and specificity for of 89Zr-10D7 in CDCP1 expressing tumors at. Significantly higher levels than normal organs and blood, with greatest tumor avidity observed at late imaging time points. Furthermore, relatively high avidity is detected in high CDCP1 expressing tumors, with reduced avidity where CDCP1 expression was knocked down or blocked. The study supports CDCP1 as a molecular imaging target for CRC in preclinical PET-CT models using the radioligand 89Zr-10D7.

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35

Korhonen, Maria H., John Brunstein, Heikki Haario, Alexei Katnikov, Roberto Rescaldani e Klaus Hedman. "A New Method with General Diagnostic Utility for the Calculation of Immunoglobulin G Avidity". Clinical Diagnostic Laboratory Immunology 6, n. 5 (1 settembre 1999): 725–28. http://dx.doi.org/10.1128/cdli.6.5.725-728.1999.

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Abstract (sommario):

ABSTRACT The reference method for immunoglobulin G (IgG) avidity determination includes reagent-consuming serum titration. Aiming at better IgG avidity diagnostics, we applied a logistic model for the reproduction of antibody titration curves. This method was tested with well-characterized serum panels for cytomegalovirus, Epstein-Barr virus, rubella virus, parvovirus B19, and Toxoplasma gondii. This approach for IgG avidity calculation is generally applicable and attains the diagnostic performance of the reference method while being less laborious and twice as cost-effective.

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36

Steffen, M. J., e J. L. Ebersole. "Effects of aging on antibody avidity to Mycoplasma pulmonis". Mechanisms of Ageing and Development 78, n. 2 (marzo 1995): 123–44. http://dx.doi.org/10.1016/0047-6374(94)01531-p.

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37

Altrich, M. L., M. Smith, M. Ling e J. F. Halsey. "Pneumococcal Antibody Avidity Evaluation in Patients with Suspected Immunodeficiency". Journal of Allergy and Clinical Immunology 125, n. 2 (febbraio 2010): AB8. http://dx.doi.org/10.1016/j.jaci.2009.12.063.

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38

Yamamoto, S., K. Tagata, Y. Ishikawa, H. Santsuka, M. Yamada, M. Morimatsu e M. Naiki. "Avidity of antibody and agglutinability of antibody-sensitized latex in latex agglutination test". Veterinary Immunology and Immunopathology 36, n. 3 (aprile 1993): 257–64. http://dx.doi.org/10.1016/0165-2427(93)90023-w.

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39

Furuya, Andrea K. M., Danielle Hunt, Kirsten St George, Alan P. Dupuis, Laura D. Kramer, Pei-Yong Shi e Susan Wong. "Use of the immunoglobulin G avidity assay to differentiate between recent Zika and past dengue virus infections". Clinical Science 133, n. 7 (aprile 2019): 859–67. http://dx.doi.org/10.1042/cs20180874.

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Abstract (sommario):

Abstract Zika (ZIKV) and dengue (DENV) virus infections elicit a robust but cross-reactive antibody response against the viral envelope protein, while antibody responses against non-structural proteins (NS) are more virus specific. Building on this premise, we have previously developed a flavivirus multiplex microsphere immunoassay (MIA) for the serologic diagnosis of ZIKV and DENV infections. This assay significantly improved diagnostic accuracy; however, MIA could not differentiate more recent from past infections, which still represents a major diagnostic challenge. Therefore, an immunoglobulin G (IgG) based avidity assay was developed and its diagnostic performance evaluated. Specimens from New York State residents were submitted to the Wadsworth Center New York State Department of Health (NYSDOH) for routine clinical testing by Zika IgM ELISA and plaque reduction neutralization test (PRNT). Using our previously developed flavivirus MIA as a platform, we developed an IgG avidity assay to discriminate recent ZIKV from past DENV infections. Zika IgM positive specimens had an average Zika IgG avidity index of 14.8% (95% CI: 11.0–18.4%), while Zika IgM negative but flavivirus MIA and PRNT positive samples had an average Zika IgG avidity index of 34.9% (95% CI: 31.1–38.7%). Specimens positive for dengue antibodies by flavivirus MIA and PRNT had an average dengue IgG avidity index of 68.7% (95% CI: 62.7–75.0%). The IgG avidity assay accurately distinguished recent ZIKV from past DENV infections in patients who traveled to dengue endemic regions. This assay could be very useful in patients with high risk of Zika complications such as pregnant women and monitoring immune responses in vaccine trials.

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40

Kourtis, Athena P., Jeffrey Wiener, Tiffany S. Chang, Sheila C. Dollard, Minal M. Amin, Sascha Ellington, Dumbani Kayira, Charles van der Horst e Denise J. Jamieson. "Cytomegalovirus IgG Level and Avidity in Breastfeeding Infants of HIV-Infected Mothers in Malawi". Clinical and Vaccine Immunology 22, n. 12 (30 settembre 2015): 1222–26. http://dx.doi.org/10.1128/cvi.00460-15.

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Abstract (sommario):

ABSTRACTCytomegalovirus (CMV) infection is common among infants of HIV-infected mothers in resource-limited settings. We examined the prevalence and timing of infant CMV infection during the first year of life using IgG antibody and avidity among HIV-exposed infants in Malawi and correlated the results with the presence of detectable CMV DNA in the blood. The Breastfeeding, Antiretrovirals and Nutrition (BAN) study randomized 2,369 mothers and their infants to maternal antiretrovirals, infant nevirapine, or neither for 28 weeks of breastfeeding, followed by weaning. Stored plasma specimens were tested for CMV IgG and antibody avidity from a random subset of infants who had been previously tested with blood CMV PCR and had available specimens at birth and at 24 and 48 weeks of age. Ninety-four of 127 infants (74.0%) tested at 24 weeks of age had CMV IgG of low or intermediate avidity, signifying primary CMV infections. An additional 22 infants (17.3%) had IgG of high avidity; 19 of them had CMV DNA detected in their blood, indicating infant infections. Taken together, these results show that the estimated prevalence of CMV infection at 24 weeks was 88.9%. By 48 weeks of age, 81.3% of infants had anti-CMV IgG; most of them (70.9%) had IgG of high avidity. The CMV serology and avidity testing, combined with the PCR results, confirmed a high rate of primary CMV infection by 6 months of life among breastfeeding infants of HIV-infected mothers. The CMV PCR in blood detected most, but not all, infant CMV infections.

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41

Ward, K. N., W. Dhaliwal, K. L. Ashworth, E. J. Clutterbuck e C. G. Teo. "Measurement of antibody avidity for hepatitis C virus distinguishes primary antibody responses from passively acquired antibody". Journal of Medical Virology 43, n. 4 (agosto 1994): 367–72. http://dx.doi.org/10.1002/jmv.1890430409.

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42

Raviprakash, Kanakatte, Kevin R. Porter, Tadeuscz J. Kochel, Daniel Ewing, Monica Simmons, Irving Phillips, Gerald S. Murphy, Walter R. Weiss e Curtis G. Hayes. "Dengue virus type 1 DNA vaccine induces protective immune responses in rhesus macaques". Microbiology 81, n. 7 (1 luglio 2000): 1659–67. http://dx.doi.org/10.1099/0022-1317-81-7-1659.

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Abstract (sommario):

A candidate DNA vaccine expressing dengue virus type 1 pre-membrane and envelope proteins was used to immunize rhesus macaques. Monkeys were immunized intramuscularly (i.m.) or intradermally (i.d.) by three or four 1 mg doses of vaccine, respectively. Monkeys that were inoculated i.m. seroconverted more quickly and had higher antibody levels than those that were inoculated i.d. The sera exhibited virus-neutralizing activity, which declined over time. Four of the eight i.m.-inoculated monkeys were protected completely from developing viraemia when challenged 4 months after the last dose with homologous dengue virus. The other four monkeys had reduced viraemia compared with the control immunized monkeys. The i.d.-inoculated monkeys showed no reduction in viraemia when challenged with the virus. All vaccinated monkeys showed an anamnestic antibody response, indicating that they had established immunological memory. Vaccine-induced antibody had an avidity index similar to that of antibody induced by virus infection; however, no clear correlation was apparent between antibody avidity and virus neutralization titres.

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43

To, Kelvin K. W., Anna J. X. Zhang, Ivan F. N. Hung, Ting Xu, Whitney C. T. Ip, Rebecca T. Y. Wong, Joseph C. K. Ng, Jasper F. W. Chan, Kwok-Hung Chan e Kwok-Yung Yuen. "High Titer and Avidity of Nonneutralizing Antibodies against Influenza Vaccine Antigen Are Associated with Severe Influenza". Clinical and Vaccine Immunology 19, n. 7 (9 maggio 2012): 1012–18. http://dx.doi.org/10.1128/cvi.00081-12.

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Abstract (sommario):

ABSTRACTThe importance of neutralizing antibody in protection against influenza virus is well established, but the role of the early antibody response during the initial stage of infection in affecting the severity of disease is unknown. The 2009 influenza pandemic provided a unique opportunity for study because most patients lacked preexisting neutralizing antibody. In this study, we compared the antibody responses of 52 patients with severe or mild disease, using sera collected at admission. A microneutralization (MN) assay was used to detect neutralizing antibody. We also developed an enzyme-linked immunosorbent assay (ELISA) which detects both neutralizing and nonneutralizing antibodies against viral antigens from a split-virion inactivated monovalent influenza virus vaccine. While the MN titers were not significantly different between the two groups (P= 0.764), the ELISA titer and ELISA/MN titer ratio were significantly higher for patients with severe disease than for those with mild disease (P= 0.004 andP= 0.011, respectively). This finding suggested that in patients with severe disease, a larger proportion of serum antibodies were antibodies with no detectable neutralizing activity. The antibody avidity was also significantly higher in patients with severe disease than in those with mild disease (P< 0.05). Among patients with severe disease, those who required positive pressure ventilation (PPV) had significantly higher ELISA titers than those who did not require PPV (P< 0.05). Multivariate analysis showed that the ELISA titer and antibody avidity were independently associated with severe disease. Higher titers of nonneutralizing antibody with higher avidity at the early stage of influenza virus infection may be associated with worse clinical severity and poorer outcomes.

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44

Sowers, Sun B., Jennifer S. Rota, Carole J. Hickman, Sara Mercader, Susan Redd, Rebecca J. McNall, Nobia Williams et al. "High Concentrations of Measles Neutralizing Antibodies and High-Avidity Measles IgG Accurately Identify Measles Reinfection Cases". Clinical and Vaccine Immunology 23, n. 8 (22 giugno 2016): 707–16. http://dx.doi.org/10.1128/cvi.00268-16.

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ABSTRACTIn the United States, approximately 9% of the measles cases reported from 2012 to 2014 occurred in vaccinated individuals. Laboratory confirmation of measles in vaccinated individuals is challenging since IgM assays can give inconclusive results. Although a positive reverse transcription (RT)-PCR assay result from an appropriately timed specimen can provide confirmation, negative results may not rule out a highly suspicious case. Detection of high-avidity measles IgG in serum samples provides laboratory evidence of a past immunologic response to measles from natural infection or immunization. High concentrations of measles neutralizing antibody have been observed by plaque reduction neutralization (PRN) assays among confirmed measles cases with high-avidity IgG, referred to here as reinfection cases (RICs). In this study, we evaluated the utility of measuring levels of measles neutralizing antibody to distinguish RICs from noncases by receiver operating characteristic curve analysis. Single and paired serum samples with high-avidity measles IgG from suspected measles cases submitted to the CDC for routine surveillance were used for the analysis. The RICs were confirmed by a 4-fold rise in PRN titer or by RT-quantitative PCR (RT-qPCR) assay, while the noncases were negative by both assays. Discrimination accuracy was high with serum samples collected ≥3 days after rash onset (area under the curve, 0.953; 95% confidence interval [CI], 0.854 to 0.993). Measles neutralizing antibody concentrations of ≥40,000 mIU/ml identified RICs with 90% sensitivity (95% CI, 74 to 98%) and 100% specificity (95% CI, 82 to 100%). Therefore, when serological or RT-qPCR results are unavailable or inconclusive, suspected measles cases with high-avidity measles IgG can be confirmed as RICs by measles neutralizing antibody concentrations of ≥40,000 mIU/ml.

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Gaensbauer, James T., Jeremy T. Rakhola, Carolyne Onyango-Makumbi, Michael Mubiru, Jamie E. Westcott, Nancy F. Krebs, Edwin J. Asturias, Mary Glenn Fowler, Elizabeth McFarland e Edward N. Janoff. "Impaired Haemophilus influenzae Type b Transplacental Antibody Transmission and Declining Antibody Avidity through the First Year of Life Represent Potential Vulnerabilities for HIV-Exposed but -Uninfected Infants". Clinical and Vaccine Immunology 21, n. 12 (8 ottobre 2014): 1661–67. http://dx.doi.org/10.1128/cvi.00356-14.

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ABSTRACTTo determine whether immune function is impaired among HIV-exposed but -uninfected (HEU) infants born to HIV-infected mothers and to identify potential vulnerabilities to vaccine-preventable infection, we characterized the mother-to-infant placental transfer ofHaemophilus influenzaetype b-specific IgG (Hib-IgG) and its levels and avidity after vaccination in Ugandan HEU infants and in HIV-unexposed U.S. infants. Hib-IgG was measured by enzyme-linked immunosorbent assay in 57 Ugandan HIV-infected mothers prenatally and in their vaccinated HEU infants and 14 HIV-unexposed U.S. infants at birth and 12, 24, and 48 weeks of age. Antibody avidity at birth and 48 weeks of age was determined with 1 M ammonium thiocyanate. A median of 43% of maternal Hib-IgG was transferred to HEU infants. Although its level was lower in HEU infants than in U.S. infants at birth (P< 0.001), Hib-IgG was present at protective levels (>1.0 μg/ml) at birth in 90% of HEU infants and all U.S. infants. HEU infants had robust Hib-IgG responses to a primary vaccination. Although Hib-IgG levels declined from 24 to 48 weeks of age in HEU infants, they were higher than those in U.S. infants (P= 0.002). Antibody avidity, comparable at birth, declined by 48 weeks of age in both populations. Early vaccination of HEU infants may limit an initial vulnerability to Hib disease resulting from impaired transplacental antibody transfer. While initial Hib vaccine responses appeared adequate, the confluence of lower antibody avidity and declining Hib-IgG levels in HEU infants by 12 months support Hib booster vaccination at 1 year. Potential immunologic impairments of HEU infants should be considered in the development of vaccine platforms for populations with high maternal HIV prevalence.

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Sandberg, E., G. Bergenholtz, H. Kahu e U. I. Dahlgren. "Low HEMA Conjugation Induces High Autoantibody Titer in Mice". Journal of Dental Research 84, n. 6 (giugno 2005): 537–41. http://dx.doi.org/10.1177/154405910508400610.

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2-hydroxyethylmethacrylate (HEMA) is a known causal agent of hypersensitivity to resin composites. We have reported that immunization with HEMA conjugated to mouse serum albumin (MSA) induces an autoantibody response in mice. In this study, we investigated both the activity and the avidity of autoantibodies induced by immunization with various HEMA conjugations to MSA. Female Balb/c mice were given MSA carrying 3, 7, 15, or 22 HEMA molecules. Antigen-specific IgG and IgE antibodies were determined by ELISA, and average antibody avidity by thiocyanate dissociation. Immunization with MSA carrying the lowest number of HEMA molecules induced a significantly higher IgG and IgE anti-MSA autoantibody response, with significantly higher IgG antibody avidity, than did the more heavily conjugated preparations. The results suggest that the lower the degree of HEMA conjugation to self-protein, the higher the risk for autoantibody production to the carrier protein. These findings suggest a mechanism of potential relevance in humans.

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Fox, Janet L., Stuart L. Hazell, Leslie H. Tobler e Michael P. Busch. "Immunoglobulin G Avidity in Differentiation between Early and Late Antibody Responses to West Nile Virus". Clinical and Vaccine Immunology 13, n. 1 (gennaio 2006): 33–36. http://dx.doi.org/10.1128/cvi.13.1.33-36.2006.

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ABSTRACT In 1999 West Nile virus (WNV) surfaced in the United States in the city of New York and spread over successive summers to most of the continental United States, Canada, and Mexico. Because WNV immunoglobulin M (IgM) antibodies have been shown to persist for up to 1 year, residents in areas of endemicity can have persistent WNV IgM antibodies that are unrelated to a current illness with which they present. We present data on the use of IgG avidity testing for the resolution of conflicting data arising from the testing of serum or plasma for antibodies to WNV. Thirteen seroconversion panels, each consisting of a minimum of four samples, were used. All samples were tested for the presence of WNV IgM and IgG antibodies, and the avidity index for the WNV IgG-positive samples was calculated. Panels that exhibited a rise in the WNV IgM level followed by a sequential rise in the WNV IgG level were designated “primary.” Panels that exhibited a marked rise in the WNV IgG level followed by a sequential weak WNV IgM response and that had serological evidence of a prior flavivirus infection were designated “secondary.” All samples from the “primary” panels exhibited low avidity indices (less than 40%) for the first 20 to 30 days after the recovery of the index sample (the sample found to be virus positive). All of the “secondary” samples had elevated WNV IgG levels with avidity indices of ≥55%, regardless of the number of days since the recovery of the index sample. These data demonstrate that it is possible to differentiate between recent and past exposure to WNV or another flavivirus through the measurement of WNV IgG avidity indices.

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Abou Basha, L. M., A. Y. Shehab, M. Abdel Fattah e A. Bassili. "Performance of IgG avidity in an area endemic for schistosomiasis in Egypt". Eastern Mediterranean Health Journal 08, n. 01 (15 marzo 2002): 172–80. http://dx.doi.org/10.26719/2002.8.1.172.

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We assessed the performance of IgG avidity in the diagnosis of acute, chronic and recent [reinfection] on top of chronic schistosomal infections in patients treated with praziquantel. Immunoglobulin levels were studied in 111 patients with Schistosoma mansoni infection and 28 partially cured patients [not responding to the first dose of praziquantel treatment and almost cured after a second one]. Before treatment all patients with schistosomiasis had elevated IgG levels, 75% of them also had increased IgM levels. Avidity index was high among all age groups. The increased IgM/IgG ratio and avidity index among children with schistosomiasis before treatment support the idea of reinfection. Treatment had no significant effect on the studied parameters. We conclude that unlike IgM and IgG antibody levels, IgG avidity test cannot be used to distinguish between recent and chronic infections.

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Fink, Ashley L., Kyrra Engle, Rebecca L. Ursin, Wan-Yee Tang e Sabra L. Klein. "Biological sex affects vaccine efficacy and protection against influenza in mice". Proceedings of the National Academy of Sciences 115, n. 49 (19 novembre 2018): 12477–82. http://dx.doi.org/10.1073/pnas.1805268115.

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Biological sex affects adaptive immune responses, which could impact influenza infection and vaccine efficacy. Infection of mice with 2009 H1N1 induced antibody responses, CD4+T cell and CD8+T cell memory responses that were greater in females than males; both sexes, however, were equally protected against secondary challenge with an H1N1 drift variant virus. To test whether greater antibody in females is sufficient for protection against influenza, males and females were immunized with an inactivated H1N1 vaccine that induced predominantly antibody-mediated immunity. Following vaccination, females had greater antibody responses and protection against challenge with an H1N1 drift variant virus than males. Antibody derived from vaccinated females was better at protecting both naïve males and females than antibody from males, and this protection was associated with increased antibody specificity and avidity to the H1N1 virus. The expression ofTlr7was greater in B cells from vaccinated females than males and was associated with reduced DNA methylation in theTlr7promoter region, higher neutralizing antibody, class switch recombination, and antibody avidity in females. Deletion ofTlr7reduced sex differences in vaccine-induced antibody responses and protection following challenge and had a greater impact on responses in females than males. Taken together, these data illustrate that greater TLR7 activation and antibody production in females improves the efficacy of vaccination against influenza.

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Sager, Heinz, Marianne Gloor, Camilla Björkman, Sandra Kritzner e Bruno Gottstein. "Assessment of antibody avidity in aborting cattle by a somatic Neospora caninum tachyzoite antigen IgG avidity ELISA". Veterinary Parasitology 112, n. 1-2 (febbraio 2003): 1–10. http://dx.doi.org/10.1016/s0304-4017(02)00416-8.

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