Since 2006, Uganda has experienced a nonchanging neonatal mortality rate of 27 out of 1,000 live births, which is higher than the global average of 19 deaths for every 1,000 live births. The purpose of this retrospective cross-sectional study was to determine factors affecting access to health services and their impact on newborn deaths in Uganda. Mosley and Chen's model for child survival in developing nations provided the framework for the study. Secondary data from the 2016 demographic and health survey (UDHS) collected by the Uganda Bureau of Statistics (UBOs) was used. A total of 7,538 cases were used and analyzed using binary logistic regression and one-way analysis of covariance (ANCOVA). The results showed attending less than 4 antenatal care (ANC) visits during pregnancy increased the odds of neonatal deaths 1.57 times, while not taking antimalarial drugs during pregnancy increased the odds of neonatal deaths 1.67 times. However, receiving 4 or more tetanus toxoid (TT) vaccine doses before pregnancy was not statistically associated with an increased risk of neonatal death (p = .597). Also, there was no significant relationship between neonatal mortality and whether distance to health facilities was a challenge (p = .276) or receiving medical assistance during childbirth (p = .420). While there were significant differences in deaths of newborns in geographic regions while controlling for the number of ANC visits (p = .023), there were no differences while controlling for all three covariates, F(4, 117) = 2.00, p = .098. Findings may be used to inform government policies on ANC and malaria prevention during pregnancy, which may reduce neonatal mortality rates in Uganda.

Although efforts have been made towards improving the health of children across the globe with notable results, neonatal tetanus (NNT) remains a major contributor to the neonatal death rates in Nigeria. This problem calls for a concerted effort by the government to achieve the revised global NNT elimination deadline of 2015. The purpose of this cross-sectional quantitative study using secondary data was to establish the prevalence of NNT in Nigeria's northeast region and to ascertain if there was any significant difference in frequency of antenatal care (ANC), trained traditional birth attendants (TBAs), and umbilical cord treatments, using single sample proportions test and chi-squared tests of independence. The framework for this research was the theory of planned behavior. The participants (N = 312) were mothers of NNT babies. In spite a continual decline in the NNT cases between 2010 (26%) and 2013 (9%), the prevalence rate of NNT was unacceptably high at 28.815%. Also, significant differences existed as mothers who gave birth to NNT babies received significantly fewer or no ANC (p < 0.001), received significantly fewer or no attention from TBAs (p < 0.001), and reported significantly fewer incidences of proper umbilical cord treatments (p < 0.001). The chi-squared tests of independence resulted in significant differences in the frequencies of mothers who received ANC between Nigerian provinces (p < 0.001) and mothers who had their baby's umbilical cord treated (p = 0.005). This study will contribute to social change by guiding health care policy makers and immunization program managers on maternal and newborn health care services and indicate ways to build capacity of the TBAs for safe home delivery/hygienic handling of umbilical cord of newborns.

Introdução: A vacina tríplice acelular de adultos (dTpa) foi introduzida no Programa Nacional de Imunizações (PNI) em novembro de 2014, sendo recomendada para gestantes e profissionais de saúde (PS) que têm contato com gestantes e recém-nascidos. De abril a dezembro de 2015, foram implementadas várias estratégias para aumentar a cobertura vacinal entre os profissionais do Instituto Central do Hospital das Clínicas da FMUSP. Objetivos: Avaliar a cobertura vacinal entre os PS após implementação de cada estratégia e ao término de um ano; avaliar as variáveis associadas à vacinação; e avaliar os principais motivos de não vacinação entre os PS com indicação para tal. Métodos: Estratégias implementadas: divulgação, no boletim do hospital, de texto relembrando da necessidade de vacinação de coqueluche; reforço da necessidade da vacinação, via correio eletrônico, para as chefias de enfermagem das Divisões de Clínica Obstétrica, Neonatologia e Anestesia; aulas sobre a vacina dTpa nas reuniões científicas das Divisões de Clínica Obstétrica e Neonatologia; e vacinação ativa dos profissionais na Divisão de Clínica Obstétrica, Neonatologia e Anestesia. A cobertura vacinal foi avaliada ao fim de cada mês até abril de 2016, por meio do sistema informatizado de vacinação usado no CRIE-HC. Foi usado o modelo de regressão de Poisson com variância robusta para avaliação das variáveis associadas com a vacinação com dTpa. As razões de prevalência foram calculadas e seus intervalos de confiança de 95% estimados. Para avaliar os motivos de não vacinação, foram realizadas ligações telefônicas para os profissionais que não receberam a vacina e aplicado questionário padronizado. Resultados: Entre os 515 PS elegíveis para vacinação, 59 não possuíam registro no sistema informatizado de vacinação e foram excluídos. Assim, este estudo incluiu 456 PS. Após as intervenções, a cobertura vacinal com dTpa aumentou de 2,9% para 41,2%. As coberturas vacinais após a implementação de cada estratégia foram: 3,7% após publicação no Boletim do hospital; 10,5% após mensagem de correio eletrônico para as chefias de enfermagem; 16,2% após aula sobre a vacina em reuniões científicas das Divisões de Clínica Obstétrica e Neonatologia; 27,9% após vacinação ativa na Divisão de Clínica Obstétrica; 40,6% após vacinação ativa na Divisão de Neonatologia e 41,2% após vacinação ativa na Divisão de Anestesia. Na análise multivariada, ser médico (a), trabalhar nas Divisões de Clínica Obstétrica ou Anestesia e ter recebido a vacina de influenza de 2015 foram associados à vacinação com dTpa. Foi feito contato telefônico com 39 profissionais que não receberam a vacina em nosso serviço; apenas 9 (23%) referiram ter recebido a vacina em outros serviços; e dos 30 não vacinados, 27 (90%) alegaram desconhecimento da recomendação. Conclusões: Conhecimento sobre a doença e a recomendação de vacinação são importantes para aumentar a cobertura vacinal entre PS. Porém, mesmo sabendo do efeito cumulativo na cobertura vacinal a cada estratégia realizada, a vacinação ativa dos PS em seus locais de trabalho parece ter sido a estratégia que mais contribuiu para o aumento da cobertura. A cobertura vacinal final de dTpa permanece baixa e maiores esforços são necessários para aumentá-la / Introduction: The acellular pertussis vaccine for adults (Tdap) was introduced in the Brazilian National Immunization Program (PNI) in November 2014, being recommended for pregnant women and healthcare workers (HCWs) who have contact with pregnant women and newborns. From April to December 2015, interventions to raise Tdap coverage among HCWs of the Instituto Central do Hospital das Clínicas were implemented. Objective: To evaluate the cumulative vaccine coverage after each intervention; identify factors associated to Tdap vaccination among HCWs; and evaluate the main reasons for HCWs not receiving Tdap. Methods: Interventions implemented: a note on the hospital\'s internal newsletter, reminding HCWs of the importance of pertussis vaccination; email to the nurse´s teams leaders strengthening vaccine recommendations; lectures on pertussis and Tdap for physicians at the clinical meetings of the Obstetrics and Neonatology Clinics; on-site vaccination by mobile teams at the Obstetrics, Neonatology, and Anesthesiology Clinics. The vaccine coverage was evaluated at the end of each month until April-2016. A multivariate Poisson regression model with robust error variance was used to evaluate variables associated with Tdap vaccination. Prevalence ratios (PR) and their 95%CI were estimated. To evaluate the reasons for HCWs not to be vaccinated, those who have not received Tdap were called by phone and a standard questionnaire was applied. Results: Among 515 HCWs eligible for immunization, 59 professionals were not registered in the vaccination data system and were excluded because information about Tdap vaccine could not be achieved. The study included 456 HCWs. After the interventions, Tdap coverage raised from 2.9% to 41.2%. The vaccine coverage after each intervention was: 3.7% after a note on the hospital\'s internal newsletter; 10.5% after email to the nurse´s teams leaders strengthening vaccine recommendations; 16.2% after lectures on pertussis and Tdap for physicians at the clinical meetings of the Obstetrics and Neonatology Clinics; 27.9% after on-site vaccination by mobile teams at the Obstetrics Clinic; 40.6% after on-site vaccination at the Neonatology Clinic and 41.2% after on-site vaccination at the Anesthesiology Clinic. In the multiple analysis, occupation, working place and having received influenza vaccination in 2015 were independently associated to Tdap vaccination. Thirty-nine HCWs that have not received Tdap were contacted by phone: 90% of them claimed they did not know the vaccine recommendation. Conclusions: Knowledge about pertussis and the recommendation of vaccination are important to raise vaccine coverage between HCWs. Even knowing the cumulative effect of each strategy on vaccine coverage, HCWs vaccination in their workplaces seems to be the most effective strategy in raising coverage. The final Tdap coverage remains low and greater efforts are needed to increase it

A tecnologia de conjugação melhorou a imunogeniddade de vacinas constituídas de polissacarídeo, especialmente em crianças. Polissacarídeos conjugados a proteínas carregadoras, como o toxóide tetânico, induzem resposta imunológica dependente de célula T e memória imunológica de longa duração. No entanto, esta tecnologia apresenta custo elevado. Assim, foi investigada a capaddade dos lipossomos de aumentar a resposta imunológica ao polissacarídeo C de Neisseria meningitidis (PSC). Camundongos foram imunizados com Iipossomos contendo PSC, conjugado toxóide tetânico-PSC ou PSC livre como controle, com dose de reforço constituída de PSC livre. Foram gerados anticorpos IgG e IgM contra PSC nos camundongos imunizados com conjugado ou Iipossomo. Os resultados mostram que lipossomos contendo PSC têm potencial para substituir a vadna conjugada toxóide tetânico-PSC. / Conjugation technology has improved the immunogenicity of polysaccharide vaccines, specially in small children. Polysaccharides conjugated to various carrier proteins, e.g. tetanus toxoid, stimulate a T cell-dependent antibody response and induce a long-term immunological memory. However, protein-polysaccharide conjugation technology is expensive and this could constitute an important drawback. Thus, immunopotentiation of Neisseria meningitidis serogroup C polysaccharide (PSC) by use of liposomes as an alternative to protein-polysaccharide C conjugates was investigated. Mice were immunized with liposomes containing PSC or tetanus toxoid-PSC conjugate or free PSC as control and boosted with free PSC. Immunogenicity of these different preparations was compared with each other. Conjugate and liposome containing PSC induced both IgG and IgM antibodies against the polysaccharide. These results show that liposomes containing entrapped PSC have potential to be used as an alternative to tetanus toxoid-PSC conjugate vaccine.

Introdução: A vacina tríplice acelular de adultos (dTpa) foi introduzida no Programa Nacional de Imunizações (PNI) em novembro de 2014, sendo recomendada para gestantes e profissionais de saúde (PS) que têm contato com gestantes e recém-nascidos. De abril a dezembro de 2015, foram implementadas várias estratégias para aumentar a cobertura vacinal entre os profissionais do Instituto Central do Hospital das Clínicas da FMUSP. Objetivos: Avaliar a cobertura vacinal entre os PS após implementação de cada estratégia e ao término de um ano; avaliar as variáveis associadas à vacinação; e avaliar os principais motivos de não vacinação entre os PS com indicação para tal. Métodos: Estratégias implementadas: divulgação, no boletim do hospital, de texto relembrando da necessidade de vacinação de coqueluche; reforço da necessidade da vacinação, via correio eletrônico, para as chefias de enfermagem das Divisões de Clínica Obstétrica, Neonatologia e Anestesia; aulas sobre a vacina dTpa nas reuniões científicas das Divisões de Clínica Obstétrica e Neonatologia; e vacinação ativa dos profissionais na Divisão de Clínica Obstétrica, Neonatologia e Anestesia. A cobertura vacinal foi avaliada ao fim de cada mês até abril de 2016, por meio do sistema informatizado de vacinação usado no CRIE-HC. Foi usado o modelo de regressão de Poisson com variância robusta para avaliação das variáveis associadas com a vacinação com dTpa. As razões de prevalência foram calculadas e seus intervalos de confiança de 95% estimados. Para avaliar os motivos de não vacinação, foram realizadas ligações telefônicas para os profissionais que não receberam a vacina e aplicado questionário padronizado. Resultados: Entre os 515 PS elegíveis para vacinação, 59 não possuíam registro no sistema informatizado de vacinação e foram excluídos. Assim, este estudo incluiu 456 PS. Após as intervenções, a cobertura vacinal com dTpa aumentou de 2,9% para 41,2%. As coberturas vacinais após a implementação de cada estratégia foram: 3,7% após publicação no Boletim do hospital; 10,5% após mensagem de correio eletrônico para as chefias de enfermagem; 16,2% após aula sobre a vacina em reuniões científicas das Divisões de Clínica Obstétrica e Neonatologia; 27,9% após vacinação ativa na Divisão de Clínica Obstétrica; 40,6% após vacinação ativa na Divisão de Neonatologia e 41,2% após vacinação ativa na Divisão de Anestesia. Na análise multivariada, ser médico (a), trabalhar nas Divisões de Clínica Obstétrica ou Anestesia e ter recebido a vacina de influenza de 2015 foram associados à vacinação com dTpa. Foi feito contato telefônico com 39 profissionais que não receberam a vacina em nosso serviço; apenas 9 (23%) referiram ter recebido a vacina em outros serviços; e dos 30 não vacinados, 27 (90%) alegaram desconhecimento da recomendação. Conclusões: Conhecimento sobre a doença e a recomendação de vacinação são importantes para aumentar a cobertura vacinal entre PS. Porém, mesmo sabendo do efeito cumulativo na cobertura vacinal a cada estratégia realizada, a vacinação ativa dos PS em seus locais de trabalho parece ter sido a estratégia que mais contribuiu para o aumento da cobertura. A cobertura vacinal final de dTpa permanece baixa e maiores esforços são necessários para aumentá-la / Introduction: The acellular pertussis vaccine for adults (Tdap) was introduced in the Brazilian National Immunization Program (PNI) in November 2014, being recommended for pregnant women and healthcare workers (HCWs) who have contact with pregnant women and newborns. From April to December 2015, interventions to raise Tdap coverage among HCWs of the Instituto Central do Hospital das Clínicas were implemented. Objective: To evaluate the cumulative vaccine coverage after each intervention; identify factors associated to Tdap vaccination among HCWs; and evaluate the main reasons for HCWs not receiving Tdap. Methods: Interventions implemented: a note on the hospital\'s internal newsletter, reminding HCWs of the importance of pertussis vaccination; email to the nurse´s teams leaders strengthening vaccine recommendations; lectures on pertussis and Tdap for physicians at the clinical meetings of the Obstetrics and Neonatology Clinics; on-site vaccination by mobile teams at the Obstetrics, Neonatology, and Anesthesiology Clinics. The vaccine coverage was evaluated at the end of each month until April-2016. A multivariate Poisson regression model with robust error variance was used to evaluate variables associated with Tdap vaccination. Prevalence ratios (PR) and their 95%CI were estimated. To evaluate the reasons for HCWs not to be vaccinated, those who have not received Tdap were called by phone and a standard questionnaire was applied. Results: Among 515 HCWs eligible for immunization, 59 professionals were not registered in the vaccination data system and were excluded because information about Tdap vaccine could not be achieved. The study included 456 HCWs. After the interventions, Tdap coverage raised from 2.9% to 41.2%. The vaccine coverage after each intervention was: 3.7% after a note on the hospital\'s internal newsletter; 10.5% after email to the nurse´s teams leaders strengthening vaccine recommendations; 16.2% after lectures on pertussis and Tdap for physicians at the clinical meetings of the Obstetrics and Neonatology Clinics; 27.9% after on-site vaccination by mobile teams at the Obstetrics Clinic; 40.6% after on-site vaccination at the Neonatology Clinic and 41.2% after on-site vaccination at the Anesthesiology Clinic. In the multiple analysis, occupation, working place and having received influenza vaccination in 2015 were independently associated to Tdap vaccination. Thirty-nine HCWs that have not received Tdap were contacted by phone: 90% of them claimed they did not know the vaccine recommendation. Conclusions: Knowledge about pertussis and the recommendation of vaccination are important to raise vaccine coverage between HCWs. Even knowing the cumulative effect of each strategy on vaccine coverage, HCWs vaccination in their workplaces seems to be the most effective strategy in raising coverage. The final Tdap coverage remains low and greater efforts are needed to increase it

Le médicament prophylactique qui a drastiquement réduit l’impact et la sévérité du tétanos sur les populations humaines est le vaccin antitétanique. Son principe actif appelé anatoxine tétanique résulte de l’inactivation au formaldéhyde de la toxine tétanique. Cette détoxification chimique est une étape critique qui détermine la sécurité, l’antigénicité et l’immunogénicité du vaccin. Pour une meilleure compréhension de ce processus chimique, à l’échelle moléculaire, nous avons dans un premier temps caractérisé l’anatoxine tétanique par chromatographie liquide couplée à la spectrométrie de masse en tandem haute résolution (LC-MS/MS) afin d’identifier et de localiser exhaustivement l’ensemble des modifications induites par le formaldéhyde sur la structure tridimensionnelle de la protéine vaccinale. Dans un second lieu, pour un meilleur suivi qualité du procédé industriel de fabrication de l’anatoxine tétanique, nous avons développé des méthodes uniques d’expertise in vitro par LC-MS/MS pour réaliser la quantification relative et/ou absolue de la toxine tétanique, de l’anatoxine tétanique, ainsi que pour effectuer la quantification relative des fragments de toxine chimiquement modifiés par le formaldéhyde. Ces outils de caractérisation sont complémentaires aux méthodes de contrôles qualités existantes et contribuent actuellement à un meilleur suivi de la reproductibilité des lots de vaccins antitétaniques / The prophylactic drug, which has drastically reduced the impact and severity of tetanus on human populations, is the tetanus vaccine. Its active ingredient called tetanus toxoid results from the inactivation of tetanus toxin with formaldehyde. This chemical detoxification is a critical step, which determines the safety, antigenicity and immunogenicity of the vaccine. For a better understanding of this chemical process, at the molecular level, we first characterized tetanus toxoid by liquid chromatography coupled with high-resolution tandem mass spectrometry (LC-MS/MS) in order to fully identify and map all the modifications induced by formaldehyde on the three-dimensional structure of the vaccine protein. In a second step, for a better quality control of the industrial process of manufacturing tetanus toxoid, we developed in vitro expertise methods by LC-MS/MS to perform the relative and/or absolute quantification of tetanus toxin, tetanus toxoid, and to carry out the relative quantification of the toxin fragments chemically modified with formaldehyde. These characterization tools are complementary to existing quality control methods and currently contribute to better monitoring the reproducibility of tetanus vaccine batches

A tecnologia de conjugação melhorou a imunogeniddade de vacinas constituídas de polissacarídeo, especialmente em crianças. Polissacarídeos conjugados a proteínas carregadoras, como o toxóide tetânico, induzem resposta imunológica dependente de célula T e memória imunológica de longa duração. No entanto, esta tecnologia apresenta custo elevado. Assim, foi investigada a capaddade dos lipossomos de aumentar a resposta imunológica ao polissacarídeo C de Neisseria meningitidis (PSC). Camundongos foram imunizados com Iipossomos contendo PSC, conjugado toxóide tetânico-PSC ou PSC livre como controle, com dose de reforço constituída de PSC livre. Foram gerados anticorpos IgG e IgM contra PSC nos camundongos imunizados com conjugado ou Iipossomo. Os resultados mostram que lipossomos contendo PSC têm potencial para substituir a vadna conjugada toxóide tetânico-PSC. / Conjugation technology has improved the immunogenicity of polysaccharide vaccines, specially in small children. Polysaccharides conjugated to various carrier proteins, e.g. tetanus toxoid, stimulate a T cell-dependent antibody response and induce a long-term immunological memory. However, protein-polysaccharide conjugation technology is expensive and this could constitute an important drawback. Thus, immunopotentiation of Neisseria meningitidis serogroup C polysaccharide (PSC) by use of liposomes as an alternative to protein-polysaccharide C conjugates was investigated. Mice were immunized with liposomes containing PSC or tetanus toxoid-PSC conjugate or free PSC as control and boosted with free PSC. Immunogenicity of these different preparations was compared with each other. Conjugate and liposome containing PSC induced both IgG and IgM antibodies against the polysaccharide. These results show that liposomes containing entrapped PSC have potential to be used as an alternative to tetanus toxoid-PSC conjugate vaccine.

Made available in DSpace on 2014-08-20T14:38:01Z (GMT). No. of bitstreams: 1 dissertacao_pedro_quevedo.pdf: 852940 bytes, checksum: 646d10b8df90285825807c9a0da507ab (MD5) Previous issue date: 2010-12-20 / A retrospective study of clostridial diagnosed in ruminants from 1978-2008 in southern Rio Grande do Sul, was conducted in the influence area of the Regional Diagnostic Laboratory of the Federal University of Pelotas. Out of 5.446 bovine specimens sent by practitioners or from necropsies performed 91 (1,67%) were diagnosed as clostridiosis. Of those, 30 (0.55%) were diagnosed as by black leg, 15 (0.27%) as bacillary hemoglobinuria, 9 (0.16%) as botulism, 9 (0.16%) as malignant edema, and 28 (0.51%) as tetanus. Out of 860 sheep specimens 49 (5.69%) were bacterial diseases and 14 (28,57%) of those were diagnosed as clostridiosis, being 10 (1.16%) cases of tetanus, 3 (0.34%) of malignant edema, and 1 (0.11%) %) of enterotoxemia. It was concluded that some clostridiosis cause important losses in livestock in Rio Grande do Sul, mainly black leg. The vaccination of young stock against black leg is recommended in the whole state. Vaccination against botulism is recommended in areas of native pastures where phosphorus deficieny occurs, and vaccination against bacillary hemoglobinuria is recommended in low lands where fasciolosis is enzootic. In cattle, tetanus may occur as outbreaks with significant economic losses, recommending also the vaccination of animals. In sheep clostridioses are less important being tetanus the more frequent. Good hygienic practices, mainly during castration or tail are recommended to prevent the disease. Enterotoxemia is a rare disease in the region, because most sheep are raised in native pastures with limited grass production; vaccination is only recommended in sheep grazing in cultivate pastures or supplemented with concentrates. / Foi realizado um estudo retrospectivo dos diagnósticos de clostridioses ocorridos na região sul do Rio Grande do Sul correspondente a área de influência do Laboratório Regional de Diagnóstico da Faculdade de Veterinária da Universidade Federal de Pelotas entre janeiro 1978 e janeiro de 2008 e acompanhados os casos de clostridioses diagnosticados nos anos 2009 e 2010. De um total de 5.446 materiais de bovinos provenientes de necropsias ou órgãos enviados 91 (1,67%) correspondiam a enfermidades causadas por bactérias do gênero Clostridium sendo 30 (0,55%) de carbúnculo sintomático, 15 (0,27%) de hemoglobinúria bacilar, 9 (0,16%) de botulismo, 9 (0,16%) de edema maligno e 28 (0,51%) de tétano. De 860 materiais de ovinos 49 (5,69%) diagnósticos corresponderam a doenças bacterianas e desses 14 (28,57%) foram de surtos de clostridioses. Dos 14 surtos de clostridioses observados em ovinos 10 (1,16%) foram de tétano, três (0,34%) de edema maligno e um (0,11%) de enterotoxemia. Concluiu-se que algumas clostridioses causam prejuízos econômicos à bovinocultura da região, principalmente o carbúnculo sintomático, recomendando-se a vacinação sistemática dos bovinos jovens contra esta clostridiose. Recomenda-se, também, a vacinação contra botulismo, em áreas de campo nativo onde ocorre carência de fósforo e contra hemoglobinúria bacilar em áreas de campos baixos onde ocorre infecção por Fasciola hepatica. Em bovinos o tétano pode ocorrer como surtos com prejuízos econômicos importantes, recomendando-se, também, a vacinação dos animais. Em ovinos as clostridioses têm pouca importância, sendo o tétano a mais frequente. Para a profilaxia desta doença em ovinos recomenda-se utilizar práticas de manejo, como descola e castração, em condições adequadas de higiene. Enterotoxemia é uma enfermidade rara na região por que a maioria dos ovinos permanece em campos nativos com limitada produção de foragem; recomenda-se a vacinação somente em animais em pastagens cultivadas ou suplementados com concentrados.

Cette thèse a pour vocation de contribuer au développement de différents immunocapteurs ampérométriques associés aux électrodes sérigraphiées (SPE). Les immunocapteurs sont des dispositifs simples associant un anticorps ou un antigène qui assurent la sélectivité à un transducteur (ici une SPE) ;ce dernier transforme la liaison anticorps/antigène en un signal mesurable (ici ampérométrique).<p>Le travail est divisé en deux volets principaux.<p>Le premier est consacré à la mise en œuvre de différents modèles d’immunocapteurs ampérométriques pour le dosage d’anticorps anti-tetani. La vaccination contre le tétanos est généralisée, toutefois pour maintenir un taux d’anticorps suffisant, il est indispensable d’administrer un rappel tous les 10 ans. Ce schéma vaccinal n’est pas toujours respecté, ce qui a pour conséquence qu’une partie de la population n’est plus protégée. Afin de déterminer le statut immunitaire du patient, il est indispensable de pouvoir déterminer le taux d’anticorps. Les immunocapteurs ampérométriques répondent à cet objectif. Plusieurs stratégies d’immobilisation de l’anatoxine tétanique (antigène) sur une SPE ont été mises en œuvre et comparées. L’une d’elles repose sur l’utilisation de microparticules superparamagnétiques pour la réaction immunologique et d’une SPE rendue magnétique par un support aimanté pour la mesure. D’autres reposent sur l’immobilisation de l’antigène et les réactions immunologiques directement à la surface de la SPE. L’utilisation de plans d’expérience, pour l’optimisation des immunoessais sur SPE est également exploitée dans ce travail. Les immunocapteurs développés ont permis de doser les anticorps anti-tetani dans le sérum de cobaye en dessous des valeurs considérées comme protectrices.<p>Dans le second volet, un immunocapteur basé sur l’utilisation de nanobodies® (NB) a été mis au point. Nous avons qualifié ce type d’immunocapteur original de nanoimmunocapteur. Le récepteur de facteur de croissance épidermique humain (HER2) a été utilisé comme cible. La protéine HER2 est considérée comme un biomarqueur important car sa surexpression provoque un type agressif de cancer du sein. Les NB sont des fragments à domaine unique dérivés d'anticorps à chaînes lourdes de camélidés. La stratégie de dosage immunologique en sandwich développée a tiré profit de la petite taille des NB pour la détection du marqueur électroactif d’oxydoréduction. La stabilité élevée des NB immobilisés a permis une durée de stockage des SPE modifiées supérieure à 3 semaines. De très courtes durées d'incubation étaient suffisantes pour obtenir une réponse satisfaisante. Le nanoimmunoessai a permis de déterminer le taux d’HER2 dopé dans des lysats cellulaires.<p> / Doctorat en Sciences biomédicales et pharmaceutiques / info:eu-repo/semantics/nonPublished

No description available.