Dissertations / Theses on the topic 'Neutralizing antibodies'
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Ovcina, Emira. "An immune response to peptides selected with neutralizing antibodies." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape4/PQDD_0019/MQ59191.pdf.
Full textBonsall, David George. "The role of neutralizing antibodies in HIV-1 infection." Thesis, Imperial College London, 2011. http://hdl.handle.net/10044/1/6360.
Full textZhang, Jianchao. "HIV-1/SIV neutralizing antibody gene delivery a novel vaccination approach /." Columbus, Ohio : Ohio State University, 2009. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1237924213.
Full textLam, Sin Man. "Neutralizing antibodies and the biological response to interferon-beta therapy." Thesis, University of British Columbia, 2010. http://hdl.handle.net/2429/26977.
Full textBurke, Karen L. "Antigen chimaeras of poliovirus." Thesis, University of Reading, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.328967.
Full textWiley, James A. "Monoclonal anti-idiotypes induce neutralizing antibodies to enterovirus-70 conformational epitopes." Thesis, University of Ottawa (Canada), 1992. http://hdl.handle.net/10393/7649.
Full textDerby, Nina Rafterman. "Designing immunogens to elicit broadly reactive neutralizing antibodies to the HIV envelope /." Thesis, Connect to this title online; UW restricted, 2007. http://hdl.handle.net/1773/9302.
Full textAlpert, Michael. "Antibodies in Vaccine Protection against SIV and HIV-1 Infection." Thesis, Harvard University, 2011. http://dissertations.umi.com/gsas.harvard:10057.
Full textYari, Fayezeh. "Expression of recombinant neutralizing anti-HIV-1 antibodies in bacteria and eukaryotic cells /." Stockholm : Karolisnska institutet, 2007. http://diss.kib.ki.se/2007/978-91-7357-079-4/.
Full textMolinos, Albert Luis Manuel. "Targeting a major HIV-1 vulnerability region: the gp41 membrane proximal external region. Balance between neutralizing and non-neutralizing antibodies and implications for vaccine design." Doctoral thesis, Universitat Autònoma de Barcelona, 2016. http://hdl.handle.net/10803/392728.
Full textLa generación de anticuerpos ampliamente neutralizantes contra el VIH-1 es el principal objetivo de una vacuna que sea capaz de controlar la epidemia causada por el virus. La glicoproteína de la envuelta del VIH-1 es el único antígeno viral expuesto en la membrana del virus y la principal diana de respuestas humorales protectoras. Dentro de esta proteína se han identificado regiones funcionales que son reconocidas por anticuerpos ampliamente neutralizantes, lo cual ha permitido establecer puntos de vulnerabilidad del virus hacia los que una vacuna debería dirigirse. En este contexto, la región externa próxima a la membrana (MPER) de gp41 es uno de los sitios de vulnerabilidad del virus más representativos, ya que está altamente conservado, juega un papel crucial en la infectividad del virus y es reconocido por anticuerpos protectores ampliamente neutralizantes. Sin embargo, su localización, contigua a la membrana, hace del MPER un dominio poco accesible, expuesto de forma transitoria, hidrofóbico y altamente influenciado por lípidos de membrana. En consecuencia, su inmunogenicidad presenta una alta complejidad que debe ser explorada en mayor profundidad. En esta tesis, aportamos nuevo conocimiento sobre la inmunogenicidad del MPER a nivel de la infección natural y en modelos animales de inmunización. Hemos evaluado miniproteínas basadas en gp41 que sobreexponen el MPER, para ser utilizadas como 1) nuevas plataformas para la detección de anticuerpos anti-MPER y 2) prototipos de inmunógenos presentados en proteoliposomas de diversa composición. Los resultados han revelado una alta inmunogenicidad del MPER en humanos, que correlaciona con la respuesta global contra la proteína de la envuelta. Esto sugiere que el sistema inmune no tiene una especial restricción para la generación de este tipo de anticuerpos. Sin embargo, los anticuerpos detectados mostraron una funcionalidad heterogénea, en términos de capacidad neutralizante y competición por diferentes epítopos, independientemente de la especificidad por el MPER. Además, los resultados fueron reproducidos en animales inmunizados. En estos últimos, conseguimos generar un alto título de anticuerpos específicos, potenciados por la incorporación en los proteoliposomas de mezclas lipídicas complejas que mimetizaban las de la partícula viral. Sorprendentemente, se generó una respuesta inmunodominante no neutralizante que solapaba con un epítopo reconocido por el anticuerpo neutralizante 2F5. En resumen, la repuesta humoral natural contra el MPER en pacientes infectados por el VIH-1 y la generada en modelos animales mediante inmunización comparten ciertas características como son la especificidad y la escasa capacidad neutralizante. Estos resultados sugieren que el balance entre la respuesta neutralizante y no neutralizante podría tener una importante relevancia en la respuesta global contra el MPER. De este modo, es necesario un mayor refinamiento de inmunógenos que sean capaces de sortear respuestas no neutralizantes. Este rediseño se verá altamente beneficiado del conocimiento generado a partir de nuevos anticuerpos monoclonales contra el MPER que reflejen la heterogeneidad funcional observada en nuestros estudios.
The elicitation of broadly neutralizing antibodies (bNAbs) against HIV-1 constitutes the major goal of an effective vaccine able to control the epidemic caused by this virus. The HIV-1 envelope glycoprotein is the only viral antigen exposed on the surface of the virus and the main target of protective humoral responses. The identification within this protein of functional regions recognized by bNAbs has delineated an HIV-1 vulnerability map that has guided efforts for rational immunogen design. In this regard, the gp41 Membrane Proximal External Region (MPER) is a major HIV-1 vulnerability site because is highly conserved, plays a major role in viral infectivity and is targeted by protective bNAbs. However, its localization, next to the viral membrane, results in a hardly accessible, transiently exposed and hydrophobic domain, strongly influenced by membrane lipids. Therefore, the immunogenicity of the MPER offers a high level of complexity that needs to be further explored. In this thesis we provide new knowledge on the MPER immunogenicity in both natural HIV-1 infection and immunization in animal models. We generated gp41-based miniproteins which properly exposed the MPER region that have been used 1) as novel platforms for MPER antibody detection and 2) as immunogen candidates presented in different proteoliposome compositions. In humans, the results revealed a strong immunogenicity of the MPER that correlated with a global response against the envelope glycoprotein suggesting no special constraints for the immune system to target this region. However, the antibodies elicited showed heterogeneous functionality in terms of neutralizing capacity and epitope competition, regardless MPER specificity. Interestingly, these results were reproduced by immunization in animal models. High antibody titers were achieved that were specially enhanced by the addition of lipid mixtures mimicking the viral membrane. Interestingly, a non-neutralizing immunodominant response against an epitope that overlapped the 2F5 neutralizing antibody binding motif was identified. Overall, the anti-MPER response in both humans and animal model settings was not correlated with the neutralizing capacity and antibodies detected or induced by immunization were preferentially non-neutralizing. Our results suggest that the balance between neutralizing and non neutralizing responses may represent an important issue in the global response against MPER. Therefore, further redesign of immunogens able to skip non-neutralizing determinants will benefit from the knowledge derived from new anti-MPER antibodies that reflect the functional heterogeneous profile observed in our studies.
Fühner, Viola [Verfasser], Michael [Akademischer Betreuer] Hust, and Stefan [Akademischer Betreuer] Dübel. "Development of neutralizing and non-neutralizing antibodies targeting known and novel epitopes on Clostridioides difficile Toxin B / Viola Fühner ; Michael Hust, Stefan Dübel." Braunschweig : Technische Universität Braunschweig, 2020. http://d-nb.info/1203299036/34.
Full textPenn-Nicholson, Adam Garth. "Characterization and evaluation of approaches to elicit Broadly Reactive Neutralizing Antibodies against HIV-1." Case Western Reserve University School of Graduate Studies / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=case1205433621.
Full textRamey, Paul Christopher. "Population density and prevalence of rabies virus-neutralizing antibodies in a northern Ohio raccoon population." Connect to resource, 2005. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1173122630.
Full textBlay, Wendy Marie. "Human immunodeficiency virus type I (HIV-1) envelope evolution and the relationship to neutralizing antibodies /." Thesis, Connect to this title online; UW restricted, 2006. http://hdl.handle.net/1773/9296.
Full textHerrman, Marissa. "Neutralizing Antibodies to Epstein Barr Virus in the Rhesus Macaque Animal Model and in Humans." Thesis, Harvard University, 2015. http://nrs.harvard.edu/urn-3:HUL.InstRepos:23845409.
Full textBiology, Molecular and Cellular
Casa, Elisa. "Cell based assays used to quantify neutralizing antibodies against SARS-CoV-2 in human samples." Doctoral thesis, Università di Siena, 2022. http://hdl.handle.net/11365/1189903.
Full textJackson, Nicholas A. C. "Properties and mechanism of action of a 17 amino acid, V3-loop-specific HIV-1 neutralizing miniantibody." Thesis, University of Warwick, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.340227.
Full textBelmonte, Antonietta. "The effects of antiviral therapy on the levels of neutralizing antibodies and antibodies mediating antibody-dependent cellular cytotoxicity in HI-1 seropositive patients /." Thesis, McGill University, 1992. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=56983.
Full textThe results indicate that patients receiving zidovudine for 36 weeks, have a diminished anti-HIV-1-ADCC directing antibody response, while the levels of these antibodies in patients receiving ribavirin or placebo remain constant. The titers of neutralizing antibodies and CD4 counts remain stable regardless of the treatment except for patients receiving ribavirin, where a decline in CD4 cells is observed. The decrease in the HIV-1 specific ADCC during zidovudine treatment parallels with the decrease in the amount of viral burden. This suggests that the two effects are somehow correlated. The impact of a washout period was also assessed. An increase in viral burden during cessation of AZT was reported which may reflect the inability of the treated host to mount a rapid immune response. As a consequence, this may lead to the deterioration of the immune status and the progression of the disease. The implications of these findings will be discussed in this study.
Reid, Phillip. "Functional Neutralizing Monoclonal Antibodies F-2-1 Against gp42 Ameliorates Disease Progression in Experimental Autoimmune Encephalomyelitis." Scholarship @ Claremont, 2018. http://scholarship.claremont.edu/cmc_theses/1822.
Full textYuan, Tingting, and 袁婷婷. "Identification of intermediate antibodies of broadly neutralizing HIV-1 human monoclonal antibody b12 and characterization of variable loops of HIV-1 envelop glycoprotein." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/196445.
Full texttw, spchen@mail atit org, and Shih-Ping Chen. "Epidemiology, pathogenesis and surveillance of the pig adapted strain of foot and mouth disease in Taiwan." Murdoch University, 2008. http://wwwlib.murdoch.edu.au/adt/browse/view/adt-MU20080813.104029.
Full textGardner, Matthew Ryan. "Targeting the CD4- and Coreceptor-Binding Sites of the HIV-1 Envelope Glycoprotein." Thesis, Harvard University, 2014. http://dissertations.umi.com/gsas.harvard:11644.
Full textSuphaphiphat, Karunasinee. "Anti-viral immune response in the semen of cynomolgus macaques and inhibition of cell to cell transmission by broadly neutralizing antibodies in an SIV/SHIV model of infection SHIV162P3 transmission by semen 1 leukocytes is efficiently 2 inhibited by broadly neutralizing antibodies." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS599.
Full textHIV-1 sexual transmission occurs mostly through contaminated semen, which contains both free virions and infected leukocytes. Moreover, factors in seminal plasma (SP) can influence both semen infectivity and host’s response. Therefore, we used the experimental model of Simian Immunodeficiency Virus (SIV) infection of macaques, to investigate semen cells infectivity and the antiviral immune responses and to evaluate the potency of broadly neutralizing antibodies (bNAbs) to block cell-to-cell virus transmission.In SIVmac251 infected cynomolgus macaques, we investigated SIV-specific innate and adaptive responses in semen, including CD8+ T cell response, humoral response and levels of cytokines, chemokines and growth factors. SIV infection induced pro-inflammatory and immunoregulatory cytokines in semen and a concomitant upregulation of activated CD69+ CD8+ T cells and CCR5+ CXCR3+ CD8+ T cells. Neither SIV-specific CD8+ T-cell responses nor humoral responses controlled seminal viral shedding. Failure to control viral replication in SIV-infected semen is related to a general inflammation and immune activation, which possibly mirrors what happen in the male genital tract and which could lead to enhanced HIV/SIV transmission.Moreover, we developed cell-to-cell transmission assays, using either TZM-bl or human PBMC as target cells and SHIV162P3-infected splenocytes and CD45+ semen leukocytes as donor cells, and evaluated bNAbs-mediated inhibition. The bNAb panel included four 1st generation bNAbs and eight 2nd generation bNAbs. A combination of 1st generation bNAbs (2F5+2G12+4E10) was able to efficiently inhibit CAV transmission, while double combination or single bNAbs showed reduced potency. Of note, individual 2nd generation bNAbs inhibited transmission as efficiently as bNAbs combinations. An anti-V3 bNAb has been selected to evaluate its potential to block cell-to-cell transmission in vivo
Wenzel, Esther Veronika Verfasser], Michael [Akademischer Betreuer] [Hust, and Stefan [Akademischer Betreuer] Dübel. "Development of recombinant human anti-diphtheria toxin neutralizing antibodies for diphtheria therapy / Esther Veronika Wenzel ; Michael Hust, Stefan Dübel." Braunschweig : Technische Universität Braunschweig, 2019. http://nbn-resolving.de/urn:nbn:de:gbv:084-2019050215003.
Full textCorti, Davide. "Analysis of the human B cell memory repertoire against infectious pathogens and isolation of broadly neutralizing human monoclonal antibodies /." Bern : [s.n.], 2008. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
Full textIanni, Elvira <1981>. "Use of E. coli OMVs as delivery system to elicit neutralizing antibodies against Chlamydia infectivity: the HtrA protein example." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2011. http://amsdottorato.unibo.it/3542/1/Ianni_Elvira_tesi.pdf.
Full textIanni, Elvira <1981>. "Use of E. coli OMVs as delivery system to elicit neutralizing antibodies against Chlamydia infectivity: the HtrA protein example." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2011. http://amsdottorato.unibo.it/3542/.
Full textRojas, Expósito Luis Alfonso. "Blood barriers for oncolytic adenovirus efficacy: study of binding to erythrocytes via CAR and albumin‐mediated evasion of neutralizing antibodies." Doctoral thesis, Universitat de Barcelona, 2017. http://hdl.handle.net/10803/404054.
Full textEls adenovirus oncolítics són agents terapèutics prometedors, degut a la seva capacitat d’infectar i eliminar selectivament les cèl·lules tumorals, sense afectar les cèl·lules normals. Tot i que la ruta preferida d’administració és la intravenosa per tal d’arribar a totes les metàstasis, la interacció del virus amb diversos components de la sang provoca la seva neutralització. Per tant, millorar l’arribada dels virus als tumors per via sistèmica és un aspecte clau per a l’èxit d’aquesta teràpia. En aquest treball s’ha estudiat la interacció de l’adenovirus serotip 5 amb els eritròcits humans a través del receptor CAR, la qual es va descriure que provocava el segrest i la inactivació del virus. Malgrat es va observar unió als eritròcits, aquesta no va reduir la transducció de cèl·lules tumorals in vitro. Degut a que els eritròcits murins no expressen CAR, es van transferir eritròcits humans a ratolins immunodeprimits per tal d’analitzar l’efecte de la interacció després de la injecció sistèmica. Tot i així, aquesta unió als eritròcits no va alterar la extravasació ni la transducció del fetge per part del virus, suggerint que la interacció és reversible i no neutralitzant. Per altra banda, l’alta prevalença d’anticossos neutralitzants contra l’adenovirus 5 en la població humana representa un obstacle molt important per la injecció intravenosa d’aquest. Per protegir l’adenovirus contra els anticossos neutralitzants s’ha inserit un domini d’unió a albúmina (ABD) a la proteïna principal de la càpside viral, la proteïna hexó. Aquest domini s’uneix a l’albúmina sèrica, recobrint el virus amb aquesta després de l’administració sistèmica. Els virus modificats amb ABD són capaços d’unir-se tant a l’albúmina humana com a la murina, fet que els permet mantenir la infectivitat i la capacitat replicativa en presència d’anticossos neutralitzants. Els adenovirus no modificats són completament neutralitzats després de la administració sistèmica en ratolins pre-immunes, mentre que els virus modificats amb ABD mantenen la capacitat de transduïr els òrgans i controlar el creixement tumoral. Els resultats presentats en aquesta tesi recolzen l’ús d’aquesta estratègia per a tractar pacients amb adenovirus oncolítics per via sistèmica.
Kaiser, Fabian Marc Philipp [Verfasser], and Axel [Akademischer Betreuer] Rethwilm. "Analysis of Cross-Clade Neutralizing Antibodies against HIV-1 Env Induced by Immunofocusing / Fabian Marc Philipp Kaiser. Betreuer: Axel Rethwilm." Würzburg : Universitätsbibliothek der Universität Würzburg, 2013. http://d-nb.info/1030475695/34.
Full textDavis, Katie L. "Analysis of HIV-1 variable loop 3-specific neutralizing antibody responses by HIV-2/HIV-1 envelope chimeras." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2008. https://www.mhsl.uab.edu/dt/2009r/davis.pdf.
Full textWiegers, Anna-Katharina [Verfasser], Michael [Akademischer Betreuer] Mach, and Thomas H. [Akademischer Betreuer] Winkler. "Neutralizing Antibodies to Antigenic Domain 5 of Glycoprotein B of Human Cytomegalovirus / Anna-Katharina Wiegers. Gutachter: Michael Mach ; Thomas H. Winkler." Erlangen : Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 2014. http://d-nb.info/1065270526/34.
Full textHashem, Anwar. "Targeting the Highly Conserved Sequences in Influenza A Virus." Thèse, Université d'Ottawa / University of Ottawa, 2013. http://hdl.handle.net/10393/24058.
Full textOlsen, Ole Andrew. "The selected lymphocyte antibody method : a novel approach for the generation and genetic analysis of human cytomegalovirus (HCMV) neutralizing monoclonal IgG antibodies." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape8/PQDD_0019/NQ46403.pdf.
Full textKim, Dhohyung. "Mechanism of Maternal Antibody Inhibition and Vaccination Strategies in the presence of Maternal Antibodies." The Ohio State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=osu1330968863.
Full textMuharemagic, Darija. "Aptamers as Enhancers of Oncolytic Virus Therapy." Thesis, Université d'Ottawa / University of Ottawa, 2015. http://hdl.handle.net/10393/32170.
Full textOtterstrom, Jason John. "Visualizing Influenza Virus Membrane Fusion: Inhibition and Kinetics." Thesis, Harvard University, 2013. http://dissertations.umi.com/gsas.harvard:11251.
Full textCheng, Yuxing. "Elicitation of antibody responses against the HIV-1 gp41 Membrane Proximal External Region (MPER)." Thesis, Harvard University, 2014. http://dissertations.umi.com/gsas.harvard:11427.
Full textMehta, Dhwani. "Development and Evaluation of an Antibody-Dependent Cellular Cytotoxicity (ADCC) Assay for Influenza A Virus." University of Cincinnati / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1613742682998356.
Full textMiyazaki, Yasuyuki. "Analyses of sensitivity to antibody-mediated neutralization and induction of neutralizing antibodies to HIV-1 Env by simian/human immunodeficiency virus-macaque model." Kyoto University, 2002. http://hdl.handle.net/2433/149868.
Full text0048
新制・課程博士
博士(人間・環境学)
甲第9660号
人博第144号
13||129(吉田南総合図書館)
新制||人||35(附属図書館)
UT51-2002-G418
京都大学大学院人間・環境学研究科人間・環境学専攻
(主査)教授 速水 正憲, 教授 津田 謹輔, 教授 松村 道一, 助教授 三浦 智行
学位規則第4条第1項該当
Miles, Brodie, Shannon M. Miller, and Elizabeth Connick. "CD4 T Follicular Helper and Regulatory Cell Dynamics and Function in HIV Infection." FRONTIERS MEDIA SA, 2016. http://hdl.handle.net/10150/622733.
Full textTabata, Rosana. "Proteção cruzada entre bacterinas antileptospirose produzidas com três representantes do Sorogrupo Sejroe. Ensaio experimental em hamsters (Mesocricetus auratus)." Universidade de São Paulo, 2002. http://www.teses.usp.br/teses/disponiveis/10/10134/tde-03052004-144546/.
Full textThe existence of cross-protection among bivalent bacterins, produced with one of three leptospires belonging to Serogroup Sejroe: hardjo (bacterin A), wolffi (bacterin B) and guaricura (bacterin C), and a strain of serovar pomona (included because of its pathogenicity to hamsters and the possibility of performing potency assay with challenge), was investigated in male hamsters (Mesocricetus auratus) by comparison of agglutinating and neutralizing antibodies titers, respectively measured by microscopic agglutination (MAT) and in vitro growth inhibition (GIT) tests. All animals received two doses of bacterins by subcutaneous route; after ten days from the second dose, they were inoculated with non-inactivated cultures of respective serovars of Serogroup Sejroe. At 21 post-challenge day (p.c.d.), all animals were bled and their sera (n=8) were joined in pools and tested by MAT and GIT. The potency assay with challenge performed only with serovar pomona was modified from protocol of USDA, but vaccines were not diluted and the immunization schedule employed two 1.0 mL vaccine doses by subcutaneous route with 10?day interval; the challenge was performed after ten days from the second dose; the number of deaths due to leptospirosis was registered; at 21 p.c.d., the survivors were sacrificed and their renal carrier state was investigated by culture of renal tissue for leptospires isolation. In the potency assay with serovar pomona, the number of infectious doses employed for challenge (100 infective units) was in accordance with the recommended range (10-1,000 infective units); respectively to bacterins A, B and C, proportions of deaths due to leptospirosis among vaccinated animals were 1/10, 0/10 and 3/10, and proportions of leptospires renal carrier among survivors were 2/9, 1/10 and 2/7. Results of MAT showed that bacterin A induced reactions against serovars hardjo and wolffi; bacterin B, against hardjo, wolffi and guaricura, and bacterin C, against guaricura; results of GIT revealed that vaccinated animals with bacterins B or C presented protection against serovar hardjo, wolffi and guaricura; however, bacterin A induced protection only against wolffi. A cross?protection was observed among serovars hardjo, wolffi and guaricura, although variations exist in the immunogenic capacity according to the strain of leptospires used for the bacterins production.
Pötzsch, Sonja [Verfasser], and Thomas [Akademischer Betreuer] Winkler. "A comprehensive antibody repertoire analysis reveals novel antigenic domains on glycoprotein B of human cytomegalovirus that induce potently neutralizing antibodies / Sonja Pötzsch. Betreuer: Thomas Winkler." Erlangen : Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 2011. http://d-nb.info/107758220X/34.
Full textMiyaji, Karina Takesaki. "Persistência de anticorpos neutralizantes anti-febre amarela em pessoas com 60 anos ou mais previamente vacinadas." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/5/5134/tde-06082015-113813/.
Full textINTRODUCTION. Yellow Fever (YF) is an acute viral disease endemic in large parts of Brazil. The main preventive measure is vaccination. This study aimed to assess the prevalence and titers of neutralizing antibodies in persons aged 60 years and older who had previously received YF 17DD vaccine, in comparison to healthy adults aged 18 to 59 years. The study also evaluated the correlation between the antibodies titers and the time elapsed since vaccination, in participants who had received a single dose of the vaccine, and the prevalence of antibodies in participants vaccinated within ten years and more than ten years before enrollment. METHODS. Participants were recruited among persons who came to the Reference Center for Special Immunobiologicals (Centro de Referência para Imunobiológcos Especiais, CRIE) of the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP) to receive any vaccine and who had previously received the YF vaccine. The following data were collected: age, ethnicity, gender, number of YF vaccine doses taken and date of last YF vaccination. CD4 T cells counts were performed using flow cytometry. YF neutralizing antibodies were measured using test of neutralization by 50% reduction of lysis plaques (PRNT50). RESULTS. Ninety-four subjects were enrolled: 46 persons aged 60 years and older (Group 1) and 48 persons aged 18 to 59 years (Group 2). There was no significant difference between the groups regarding gender, ethnicity, number of YF vaccine doses previously received, time since the last dose and CD4+T cells count. There was no difference in the prevalence of YF neutralizing antibodies between the groups (87% and 93.8% in Groups 1 and 2, respectively, p=0.263). The log-transformed Geometric Mean Titer (GMT) of YF neutralizing antibodies was higher in the younger group (3.77 log10mUI/mL) in comparison to the older group (3.64 log10mUI/mL), and this difference was statistically significant (p=0.022). There was no correlation between YF neutralizing antibodies titers and time elapsed since vaccination among the participants who had previously received a single dose of YF vaccine, with the two groups analyzed together. There was no significant difference in the prevalence of neutralizing antibodies among participants who received a single dose of YF vaccine within ten years or more than 10 years before enrollment. CONCLUSIONS. Further studies on antibodies persistence in the elderly are necessary, considering the possibility of compromised immune response to vaccines due to immunosenescence
Lucar, Olivier. "Implication des cellules Natural Killer dans la physiopathologie des infections chroniques VIH et VHC : application à des stratégies thérapeutiques." Thesis, Paris 6, 2017. http://www.theses.fr/2017PA066471/document.
Full textHuman Immunodeficiency and Hepatitis C (HIV and HCV) chronic infections are at the origin of pandemics. Despite advance drug treatments, their relationship with the immune system is not resolved and is still required to establish new therapeutic strategies. Natural Killer (NK) cells are major antiviral effectors of the immune system and are important for innate and adaptive immune processes. They mediate cytotoxicity and immunoregulation via various activator and inhibitor receptors that are triggered upon interaction with their cognate ligands. Among all receptors, I particularly took an interest in Natural Cytotoxicity Receptors NKp30 and NKp44. Interestingly, the lab previously identified a conserved HIV-1 gp41 épitope that induce expression of NKp44 ligand on CD4+ T cells making them susceptible to lyses by NK-NKp44+ cells. After various studies, the lab established a vaccine strategy based on a peptide from the conserved gp41 épitope that induced in mice Neutralizing Antibodies (Nab W614A-3S) against HIV-1 infection. Whereas HIV-2 infection could be considered as a HIV control infection unique model, data on NK cells are very limited. We found a down-modulation of NKp30 receptor and an increased of its ligands that lead to functional impairments of NK cells and could represent a new viral persistence mechanism. Then, during the HCV chronic infection we found a high proportion of intrahepatic NK cells expressing NKp44 that correlates with fibrosis and viral load. Furthermore we identified a conserved épitope of HCV core protein that induced NKp44 ligand on hepatic cell lines. These data suggest that destruction of hepatocyte might occur by a similar mechanism observed during HIV-1 infection. Finally, a study on HIV-1 controllers patients allow us to identify the presence of Nab W614A-3S that correlates with viral control and the preservation of functional CD4+ T cells. These data confirm the potency of this Nab and their induction by vaccination has been also confirmed in rabbit and macaques. Thus, these studies highlight new data regarding relationship between NK cells and HIV or HCV that could represent new therapeutic approaches. These studies especially confirm the potency of Nab W614A-3S to implement a vaccine against HIV-1
Argolo, Angela Ferreira Lopes de Teive e. "Circulação dos vírus dengue no estado de Goiás: vigilância laboratorial (1994-2013) e perfil de anticorpos neutralizantes sorotipo específico durante o surto de 2013 em Goiânia." Universidade Federal de Goiás, 2014. http://repositorio.bc.ufg.br/tede/handle/tede/8774.
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Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq
Fundação de Amparo à Pesquisa do Estado de Goiás - FAPEG
Dengue is an endemic disease in Goias state with current circulation of the four serotypes. In the last five years has been occurred a significant increase in cases, hospitalizations and deaths caused by dengue in the region. In this thesis the first manuscript analyzed data from the virological surveillance of DENV in Goias during 1994-2013. Virus isolation in C6/36 (A.albopictus) cell culture followed by indirect immunofluorescence using monoclonal antibodies were performed in LACEN-GO. During the study period the four serotypes have been identified with introduction of DENV-1 in 1994, DENV-2(1998), DENV-3(2002) and DENV-4(2011). Among 21,684 virus isolation tests performed 4,839(22.3%) were positive. DENV-1 was isolated in 3,023(62.5%), DENV-3 in 1,051 (21.7%), DENV-4 in 413(8.5%) and DENV-2 in 352(7.3%) samples respectively. There were changes in the predominance of serotypes throughout the study period with dominance of DENV-1 between 1994-2002 and 2009-2011, DENV-3 in 2003-2008 and DENV-4 in 2013. The DENV-2 was never prevalent among serotypes isolated in LACEN-GO. The time series of the virological surveillance of dengue in Goias showed the introduction and the temporal sequence of circulation of DENV in the state. This study contributes to characterize the epidemiological scenario of dengue in Goias with possible implications for epidemiological surveillance of the disease in the region. The second manuscript evaluated the presence of dengue serotype-specific neutralizing antibodies (NAb) in patients involved in a clinical dengue cohort established during epidemic of 2012-2013 in Goiania, state of Goias. Among 452 participants of the cohort we analyzed the paired samples from 60 patients classified as severe dengue (n=40) or dengue fever (n=20). The eligibility criteria were confirmation of the infection by IgM, NS1Ag and /or RT-PCR; IgG positive in at least one of the samples. Monotypic or multitypic response were defined: PRNT50≥1/20 for only one serotype or ≥1/20 for two or more serotypes simultaneously. The infecting serotype was defined by ≥4 fold increase in the title of NAb in paired samples. Overall 73.3% of patients had NAb against DENV-4, 68.3% against DENV-1, 68.3% against DENV-2 or 61.6% against DENV-3. The patients' ages ranged from 3 to 81 years. Regardless of age group 85% of patients had multitypic response while 15% had monotypic response. Patients infected with DENV-4 showed the greatest difference in NAb titers in comparison to other serotypes indicating predominance of seroconversion for serotype 4. There was no correlation among preexistent NAb and disease severity. The characterization of dengue serotype-specific immune response is important to study the relationship of preexistence of neutralizing antibodies with clinical outcomes of disease also facing the perspective of introducing of antidengue vaccines to identify protective immunity.
A dengue é uma doença endêmica em Goiás com atual circulação dos quatro sorotipos virais com aumento expressivo no número de casos, hospitalizações e óbitos pela doença de forma acentuada nos últimos cinco anos. Na presente tese o primeiro manuscrito analisou os dados da vigilância virológica dos DENV em Goiás no período de 1994-2013. Os testes de isolamento viral em cultura celular C6/36(A.albopictus) seguido de imunofluorescência indireta utilizando anticorpos monoclonais foram realizados no LACEN-GO. No período do estudo, os quatro sorotipos virais foram identificados no estado com introdução do DENV-1 em 1994, DENV-2(1998), DENV-3(2002) e DENV-4(2011). Do total de 21.684 testes de isolamento viral 4.839(22,3%) foram positivos. DENV-1 foi isolado em 3.023(62,5%), DENV-3 em 1.051(21,7%), DENV-4 em 413(8,5%) e DENV-2 em 352(7,3%) amostras. A predominância dos sorotipos virais alternou ao longo do período com DENV-1 dominante entre os anos de 1994-2002 e 2009-2011, DENV-3 entre 2003-2008 e DENV-4 em 2013. O DENV-2 nunca foi predominante entre os sorotipos isolados no LACEN-GO. A série histórica da vigilância virológica da dengue em Goiás mostrou a introdução e a sequência temporal da circulação dos DENV no estado. Este estudo contribui para a caracterização do cenário epidemiológico da dengue em Goiás com possíveis implicações nas ações de vigilância epidemiológica da doença na região. O segundo manuscrito avaliou a presença de anticorpos neutralizantes (AcN) antidengue sorotipo específico em pacientes de uma coorte clínica de dengue estabelecida durante a epidemia de 2012-2013, em Goiânia-GO. Entre os 452 participantes da coorte, analisamos amostras pareadas de 60 pacientes classificados como dengue grave (n=40) ou dengue (n=20). Os critérios de elegibilidade foram a confirmação da infecção por IgM, NS1Ag e/ou RT-PCR; IgG positivo em pelo menos uma das amostras. Resposta monotípica ou multitípica foram definidas por PRNT50≥1/20 para apenas um sorotipo viral ou ≥1/20 para dois ou mais sorotipos virais simultaneamente. O sorotipo viral infectante foi definido por um aumento ≥4 vezes no título dos AcN em amostras pareadas. No total 73,3% dos pacientes apresentaram AcN contra DENV-4, 68,3% contra DENV-1, 68,3% contra DENV-2 ou 61,6% contra DENV-3. A idade dos pacientes variou de 3 a 81 anos. Independente da faixa etária 85% dos pacientes apresentaram resposta multitípica enquanto 15% tiveram resposta monotípica. Pacientes infectados por DENV-4 apresentaram a maior diferença de títulos de AcN em comparação com outros sorotipos virais indicando predominância de soroconversão para o sorotipo 4. Não houve correlação entre preexistência de AcN com a gravidade da doença. A caracterização de resposta imune sorotipo específica é importante para estudar a relação de anticorpos neutralizantes preexistentes com a gravidade clínica da doença, bem como frente à perspectiva de introdução de vacinas antidengue para identificar a imunidade protetora.
Grundner, Christoph. "HIV-1 immune escape and neutralizing antibodies solid phase proteoliposomes containing HIV-1 envelope glycoproteins as antigens and immunogens and HIV-1 core envelope glycoproteins deficient in T-helper epitopes /." [S.l.] : [s.n.], 2002. http://deposit.ddb.de/cgi-bin/dokserv?idn=965908992.
Full textHenzel, Andréia. "Experimental pathogenesis of acute and latent genital infection by bovine herpesvirus type 1.2 in heifers." Universidade Federal de Santa Maria, 2012. http://repositorio.ufsm.br/handle/1/4062.
Full textThe feline calicivirus (FCV) and the felid herpesvirus type 1 (FeHV-1) are the main agents of the respiratory tract diseases of felines. Both viruses are distributed worldwide, however its distribution and prevalence in Brazil are not well known. In the present thesis we describe the isolation and one serosurvey of FCV and FeHV-1 in some counties of the Rio Grande do Sul State, Brazil; and the molecular characterization of the capsid protein gene of FCV isolates is also described. In Chapter 1, we describe the epidemiologic survey of FCV and FeHV-1 through investigation of the conjunctival, nasal, oral and oropharyngeal swabs from 302 domestic cats. The viral isolation was performed in Crandell-Reese feline kidney cells and the isolates were submitted to PCR and RT-PCR for confirmation of the presence of the FeHV-1 and FCV, respectively. Fifty five (18.2%) of the 302 cats analyzed were positive for the viral isolation; when tested by PCR, 29 cats (52.7%) were shedding the FCV, 21 (38.2%) shedding FeHV-1, and 5 cats (9.1%) shedding both viruses. In addition, isolates of FCV and FeHV-1 were standardized to be used as control in the PCR and virus neutralization (VN) assays (serological technical used in chapter 3 of the thesis). The SV65/90 (FCV) and the SV534/00 (FeHV-1) isolates were defined as standard viruses for the assays. In Chapter 2, the molecular characterization of 13 FCV isolates is described; ten isolates came from the survey performed in chapter 1, two were deposited in the virology laboratory of the UFSM and one was obtained from a cat with gingivitis-stomatitis syndrome. The ORF2 (open reading frame) region that codifies the major protein of the viral capsid was sequenced, which includes an immunodominant region of the virus. The ORF 2 was analyzed at the nucleotide and amino acid levels and these data was used for phylogenetic studies of the 13 Brazilian isolates of FCV. These isolates were compared to ten reference strains of FCV and to the San Miguel sea lion virus type 1 (SMSV-1) as an outgroup in phylogenetic study. The primers were designed using the complete sequence of FCV-F9. The comparison of the 13 Brazilian isolates with the F9 strain revealed a large molecular diversity among them, concentrated mainly along the linear epitopes of the region. The Chapter 3 describes a serosurvey against FCV and FeHV-1 in serum samples from domestic feline. From the 630 samples tested by the VN assay, 53.6% (338/630) were positive to one or both viruses with a prevalence of 39.2% for neutralizing antibodies against FCV and 30.6% for FeHV-1. The results from the present study demonstrated that the FCV and FeHV-1 are circulating among the feline population examined, and also, the presence of carriers of the viruses among these cats. Besides, the molecular characterization of the FCV evidenced the great genetic variability of the Brazilian isolates when compared to vaccine and reference strains.
O calicivírus felino (feline calicivirus FCV) e o herpesvírus felino tipo 1 (felid herpesvirus type 1 FeHV-1) são os principais agentes das doenças do trato respiratório dos felinos. Ambos os vírus são mundialmente distribuídos, mas no Brasil sua distribuição e prevalência são ainda pouco conhecidas. Na presente tese descrevemos o isolamento e sorologia do FCV e do FeHV-1 em alguns municípios do estado do Rio Grande do Sul (RS), Brasil; e a caracterização molecular do gene da proteína do capsídeo de isolados de FCV. No Capítulo 1, descreve-se o isolamento do FCV e do FeHV-1 por meio da coleta de suabes (conjuntival, nasal, oral e orofaringeano) de 302 gatos domésticos. O material coletado foi inoculado em cultivo celular de origem felina (CRFK) e submetidos a PCR e RT-PCR para confirmação em FeHV-1 e FCV, respectivamente. Dos 302 gatos analisados, 55 (18,2%) foram positivos no isolamento; e quando testados por PCR, 29 dos 55 gatos (52,7%) excretavam o FCV, 21 (38,2%) excretavam o FeHV-1 e 5 gatos (9,1%) apresentavam ambos os vírus. Além dessa descrição, realizou-se a padronização de um isolado de FCV e de FeHV-1, para serem utilizados como controle nas técnicas de PCR e na vírus neutralização [VN] (técnica sorológica utilizada no capítulo 3 da tese). O SV65/90 (FCV) e o SV534/00 (FeHV-1) foram os isolados definidos como vírus-padrão. No Capítulo 2, incluímos o estudo sobre a análise molecular de 13 isolados de FCV; dez isolados foram obtidos a partir do material descrito no capítulo 1, dois estavam armazenados no laboratório de virologia da UFSM e um foi obtido de um gato acometido pela síndrome gengivo-estomatite. A região analisada foi o gene da proteína do capsídeo, codificado pela ORF2 (open reading frame), na qual se localizam as regiões imunodominantes do FCV. A ORF2 foi analisada em nível de nucleotídeos e aminoácidos; e uma análise filogenética dos 13 isolados brasileiros de FCV, incluindo dez cepas de referência e o vírus dos leões marinhos de San Miguel tipo 1 (San Miguel sea lion virus type 1 SMSV-1) como um outgroup, foi também realizada. Os primers foram desenhados com base na sequência completa do genoma da cepa de referência a FCV-F9. Quando os 13 isolados brasileiros de FCV foram comparados a cepa F9, detectou-se grande diversidade molecular nas regiões variáveis do gene e nos epitopos lineares mapeados. O Capítulo 3 contem um estudo sorológico contra FCV e FeHV-1 em amostras de soro de felinos domésticos. Das 630 amostras testadas pela VN, 53,6% (338/630) foram positivas para um ou ambos os vírus; sendo a prevalência de anticorpos neutralizantes contra o FCV de 39,2% e do FeHV-1 de 30,6%. Os resultados aqui apresentados demonstram a circulação do FCV e do FeHV-1 na população de gatos domésticos analisados, assim como, a presença de gatos portadores para ambos os vírus. Além disso, a caracterização molecular do FCV demonstrou a grande variabilidade genética dos isolados brasileiros em comparação às cepas vacinais e às de referência.
Rousset, Claire. "Coévolution entre les glycoprotéines d'enveloppe du VIH et les anticorps neutralisants à large spectre ciblant la région du glycane N332." Thesis, Université Grenoble Alpes (ComUE), 2018. http://www.theses.fr/2018GREAV071/document.
Full textHIV has been the cause of the AIDS pandemic since the 1980s. With over a million new infections each year, a prophylactic vaccine is needed to stop the virus spread. Among vaccine strategies, the induction of broadly neutralizing antibodies is one of the most promising, as they could protect against infection by the huge genetic diversity of circulating HIV strains. To date, no immunogen has induced such antibodies, but they have been isolated from HIV infected people. Indeed, a small fraction of infected individuals eventually develops broadly neutralizing antibodies that target vulnerable and conserved sites of the envelope glycoprotein. The region of the high-mannose patch, centred around a glycan at position N332 of gp120, is the most frequently targeted, and is therefore attractive from a vaccination standpoint.In order to better understand how antibodies targeting the high-mannose patch develop, we studied a donor selected from the International AIDS Vaccine Initiative Protocol C cohort with exceptional serum neutralizing activity. We isolated two antibody lineages targeting the N332 region from this individual's blood cells, which we characterized for their neutralizing activity and mapped their epitope. We also mapped the paratope of an antibody lineage from another Protocol C donor, also targeting the N332 region. Our results show the great diversity of solutions to achieve broad neutralization against this region. Lineage studies, as we have undertaken, provide an understanding of how antibody-virus coevolution leads to the selection of broadly neutralizing antibodies. The ultimate goal is to use this knowledge to develop immunogens and immunization protocols, to induce specific antibody lineage and drive their evolution towards broad neutralization
Reinhard, Henrike Christiane. "Struktur-Funktions-Beziehung der HCMV-kodierten Fcgamma-Rezeptoren gp34 und gp68." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2010. http://dx.doi.org/10.18452/16124.
Full textNeutralizing IgGs play a key role in diminishing virus infectivity by inhibiting the entry into host cells. Additionally, IgG-bound particles may be inactivated by virolysis through the activation of complement. Surface receptors specific for the Fc domain of IgG represent host proteins, connecting humoral and cellular immune responses. Also members of the herpes virus family code for proteins with Fc binding properties, implying functions that could intervene with antibody-dependent effector mechanisms. The presence of gp34 and gp68 on the virion membrane raised the question whether they are able to inhibit neutralising IgG and complement-mediated virolysis. The HSV-1-encoded FcyR gE was described to affect neutralisation and virolysis. Despite extensive analysis, there were no implications found that gp34 or gp68 interfere with neutralising IgG or virolysis in vitro. However, our lab could demonstrate that gp34 and gp68 selectively inhibit the IgG-dependent activation of the different host FcyRs. In contrast to the cFcyRs Fc recognition by gp34 and gp68 occurs independently of N-linked glycosylation of IgG, which points to a different binding mechanism among host and viral FcyRs. By taking advantage of a mutated Fc fragment, overlapping binding regions of the HSV-1 gE and gp68 were identified. For gp68 the amino acids 71-292 including the N-glycans are strictly required for Fc binding in a 2:1 stoichiometry. Interestingly, gp34 forms covalently linked homo-oligomers in infected cells and on the virion. Based on the minimal binding domain comprising the amino acids 24-140 of gp34, targeted cysteine exchange mutants revealed that oligomer formation by gp34 is absolutely required for Fc binding. In contrast to gp68, the Fc binding characteristics of gp34 appears to be unique among the known FcyRs. These findings allow us to postulate that even if the HCMV-encoded FcyRs are redundantly expressed the mechanistic details and binding properties are selective.
Fiebig, Uwe. "Induktion neutralisierender Antikörper gegen transmembrane Hüllproteine von Retroviren." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2008. http://dx.doi.org/10.18452/15746.
Full textPorcine xenotransplants may offer a potential solution to the problem posed by the limited supply of allotransplants. However, xenotransplantation may be associated with the risk of transmission of microorganisms, in particular of porcine endogenous retroviruses (PERVs) that are an integral part of the porcine genome and able to infect human cells in vitro. Possible strategies to prevent virus transmission include the development of PERV knockout animals or of effective vaccines. When antisera prepared against the main structural proteins of PERV were screened, goat and rat antisera against the recombinant ectodomain of the transmembrane envelope protein p15E were found to neutralize PERV infectivity. Epitope mapping using overlapping peptides revealed two epitopes, one near the fusion peptide (E1, GPQQLEK) and the other near the transmembrane domain (E2, FEGWFN). These sequences are identical for all PERVs and are highly conserved among all gammaretroviruses. Interestingly, neutralizing antibodies isolated from AIDS patients that recognize regions partially homologous with E2 (mAb4E10, LWNWFN) or located in close proximity to E2 (mAb2F5, ELDKWA) are known to neutralize a broad range of HIV-1 strains. The binding mechanisms of these HIV neutralizing antibodies were analyzed in ELISA experiments and in vitro inhibition assays. The results indicate that the two most broadly reactive HIV-1 envelope gp41 human mAbs are specific for a discontinuous epitope composed of the E1 and the E2 domain. If so, these two transmembrane protein domains in different retroviruses act as effective targets for neutralizing antibodies and may provide the basis for effective antiretroviral vaccines.