La vaccination est une des meilleures procédures de prévention coût-efficaces. Des couvertures vaccinales non adéquates présentent des problèmes de Santé publique considérables. Réduire ou éliminer les occasions manquées de vaccination (OMV) dans les régions les plus vulnérables permettrait d’y augmenter la couverture vaccinale. L’Inde a un des plus grands programmes de vaccination dans le monde, cependant il y existe d’importants gradients de couvertures vaccinales d’une région à l’autre. Objectifs : Cette étude visait à estimer la prévalence des OMV chez des jeunes enfants en zone rurale de Hardoi en Inde et identifier les potentiels déterminants et facteurs prédictifs des OMV. Méthodes : Les données secondaires d’une étude pré-post ont été utilisées pour mener une étude transversale. Les OMV ont été définies selon la définition de l’Organisation mondiale de la santé. Deux sources d’information sur le statut vaccinal ont été considérées : mémoire des mère ou carnet de vaccination (M/C) pour les analyses principales; et carnet de vaccination seulement (CS) en analyse de sensibilité. La prévalence des OMV dans la première année de vie (OMV-1AV) chez les enfants de 12 à moins de 24 mois et celle des OMV pendant la période optimale de vaccination (OMV-PO) chez les 0 à moins de 24 mois ont été calculées par sexe et bloc administratif. Les potentiels déterminants des OMV ont été identifiés à l’aide de modèles hiérarchiques. Des modèles prédictifs ont été construits pour identifier les facteurs qui permettraient de mieux cibler les enfants plus à risque d’OMV: leur pouvoir prédictif a été évalué avec la statistique c. Résultats : La prévalence des OMV-1AV selon la source M/C est de 19,3% ; celle selon CS est de 76,0%. La prévalence des OMV-PO selon M/C est de 14,6% alors qu’elle est de 65,7% selon CS. Pour les OMV-1AV et les OMV-PO, la prévalence variait d’un vaccin à l’autre mais seulement selon CS. Les déterminants des OMV varient selon la source d’information sur le statut vaccinal. Les principaux potentiels déterminants selon M/C sont: problèmes logistiques (OMV-1AV Rapport de cotes (RC) = 3,38; OMV-PO RC = 2,59); malaise ressenti chez l’enfant (OMV-1AV RC = 0,37; OMV-PO RC = 0,52); refus des vaccinateurs de vacciner sans avoir le carnet de vaccination (OMV-1AV RC = 5,66; OMV-1AV RC = 5,23); effets secondaires (OMV RC = 8,24; OMV-PO RC = 5,62); et le fait qu’un membre de la famille s’oppose à la vaccination de l’enfant; (OMV-1AV RC = 4,03; OMV-PO RC = 4,61). Des modèles prédictifs efficaces ont été construits et présentaient des statistiques c variant entre 0,72 et 0,79. Certains facteurs permettaient d’améliorer le pouvoir prédictif des modèles sans être nécessairement des potentiels déterminant des OMV tel que le temps de déplacement à pied entre le ménage et le centre de vaccination. Retombées : Les résultats suggèrent que la situation des OMV est complexe que ce soit du point de vue de la source d’information sur le statut vaccinal, de l’identification de leurs potentiels déterminants ou sur la capacité à cibler les individus les plus à risque. Les divergences au niveau des estimations de la prévalence selon la source d’information soulignent l’importance d’assurer un meilleur contrôle de la validité des sources d’information afin de maximiser l’exactitude des informations fournies. / Introduction: Missed opportunities for vaccination (MOV) affect vaccination coverages and contribute to create considerable vaccination gradient between and within regions. In India, despite major vaccination accomplishments, important vaccination gradients persist. MOV have been reported but the situation is not well known in many parts of the country. Aim: Quantify MOV in children in rural Hardoi district and identify potential determinants and predictive factors. Methods: We defined MOV using the definition of the World Health Organization. Our outcomes were missed opportunities for vaccination in first year of life (MOV-FYL) and missed opportunities for on-time vaccination (MO-OTV). We used a cross-sectional design. Vaccination status was verified according to two sources: by mothers’ recalls OR children vaccination card for the main analysis; and by vaccination card only for sensitivity analysis. We calculated the prevalence of both outcomes in a clustered population of 0 to under 24month-old children recruited in a census-like manner from rural area in Hardoi, India. We used multilevel binary logistic regression to identify potential determinants of MOV and multivariable logistic regression to built prediction models. Results: The prevalence was 19.30% and 14.39% for MOV-FYL and MO-OTV respectively. There were little variations across child sex and vaccines. However, among vaccination cardholders, the prevalence was 75.99% and 65.73% for MOV-FYL and MO-OTV respectively and varied across vaccines. Marked potential determinants using the main source of information about vaccination status were: logistics problems (MOV-FYL Odds Ratio (OR) = 3.38; MO-OTV OR = 2.59); child feeling unwell (MOV-FYL OR = 0.37; MO-OTV OR = 0.52); the refusal of health provider to vaccinate without the vaccination card (MOV-FYL OR = 5.66; MO-OTV OR = 5.23); side effects (MOV-FYL OR = 8.24; MO-OTV OR = 5.62); and family member not allowing vaccination (MOV-FYL OR = 4.03; MO-OTV OR = 4.61). Predictive models for MOV-FYL and MO-OTV yielded c statistics around 0.72 and 0.79 respectively and had the best sensitivity/specificity balance when used in a population with 15%-20% probability of MOV. Conclusion: Our study revealed that quantifying the prevalence of MOV is rather complexed. The source of information about vaccination status is key to obtain the best estimates, hence the knowledge on the reliability of the information from the card or obtained from recalls is a must. Many potential modifiable determinants should be explored and there is potential for predictability: interventions should be developed to reduce risks of MOV in targeted individuals, increase vaccination coverage and reduce vaccination gradients.

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OBJECTIVE/ METHOD The study examined implementation challenges faced by primary health care workers within the Ekurhuleni Metropolitan Municipality in Gauteng South Africa. Data collection was based on semi-structured interviews carried out on a purposive sample (n=19) of frontline clinicians working within the district as primary health care practitioners. RESULTS Participants confirmed that work within the primary health care service disproportionately focussed on curative and rehabilitative functions of their roles with little prioritisation of preventive and promotive interventions. Primary identified reasons included, institutional culture that prioritised short-term curative approaches. Clinicians also cited a range of other organisational barriers, such as – poor strategic planning, and a lack of understanding of health promotion and illness prevention. CONCLUSIONS Although the challenges that exist in implementing primary health care are clearly understood, clinicians perceive the solutions for these as being within the control of policy makers and those with power within the organisation. / Health Studies / M.A. (Public Health)

This study investigated caregivers' perceptions with regard to vaccine-preventable diseases in terms of six constructs of the Health Belief Model. A qualitative research design that is explorative, descriptive and contextual in nature was employed in order to understand and describe the perceptions influencing access and utilisation of services that lead to missed immunisation opportunities and consequently outbreaks of vaccine-preventable diseases. The data-collection techniques were individual unstructured in-depth interviews, field notes and clinical records. The sample consisted of twenty two (N=22) caregivers who volunteered to be interviewed. The study has highlighted that caregivers' perceptions or cognitive factors play an important role for having children in completing immunisation schedule to protect the public from vaccine-preventable diseases. It is recommended that mass media programmes are needed to address the role of vaccines in reducing high morbidity and mortality rates caused by vaccine preventable diseases and improvement in access to immunisation services. / Health Studies / MPH (Health Studies)

La vaccination muqueuse est un moyen efficace de lutter contre les pathogènes qui utilisent les muqueuses comme porte d’entrée. Cependant, la vaccination muqueuse avec des antigènes non réplicatifs nécessite l’utilisation d’adjuvants. Les molécules de la famille de la toxine du choléra, l’entérotoxine thermolabile d’E.coli (LT), la toxine du choléra (CT) ainsi que le mutant LT-R192G et les sous-unités B non toxiques de ces toxines (LTB et CTB) ont été montrées augmenter les réponses immunitaires contre des antigènes coadministrés par voie muqueuse. Cependant leur mécanisme d’action est complexe et reste encore mal connu et des différences entre molécules entières et sous-unités B ont été rapportées ainsi que, pour une même molécule, des différences selon le modèle utilisé. Dans ce travail, nous avons étudié les effets de ces cinq molécules sur les réponses anticorps ainsi que sur les lymphocytes T CD4 dans un modèle murin d’immunisation intrarectale avec des pseudoparticules virales de rotavirus (VLP-2/6). Chez les souris non immunisées, nous avons montré que ces molécules, à l’exception de la CTB, diminuent in vitro les lymphocytes T régulateurs naturels CD4+CD25+Foxp3+, probablement par un mécanisme d’apoptose. Chez les souris immunisées, toutes les molécules étudiées induisent une même réponse anticorps sérique et fécale spécifique des VLP-2/6, qu’il s’agisse des molécules entières connues pour leur fort pouvoir adjuvant ou des sous-unités B qui, elles, ont été rapportées avoir un plus faible effet adjuvant voire un effet tolérogène dans certaines études. Concernant la réponse T CD4, les réponses spécifiques de l’antigène et de l’adjuvant ont été analysées. Des différences importantes ont été mises en évidence entre ces molécules. Notamment, seules les molécules entières (LT, LT-R192G et CT) induisent la production d’IL-2 et l’activation de lymphocytes T CD4+CD25+Foxp3- mémoires spécifiques de l’antigène tout en permettant la mise en place d’une régulation médiée par des lymphocytes T régulateurs CD4+CD25+Foxp3+ (boucle d’autorégulation), qui pourraient jouer un rôle majeur lors d’une réponse secondaire, afin d’éviter les réactions inflammatoires délétères. Malgré ces différences, toutes les molécules étudiées induisent la production d’IL-17, suggérant le rôle majeur de cette cytokine dans l’effet adjuvant.L’influence de la voie d’administration sur ces effets est en cours d’étude grâce à la comparaison avec la voie intranasale / Mucosal immunization is an important goal of vaccine development to protect against pathogens that use mucosa as portals of entry. However, the use of non-replicating antigens requires the addition of adjuvants.Cholera-like enterotoxins, cholera toxin (CT) from Vibrio cholerae and the heat-labile enterotoxin (LT) from toxinogenic strains of E. coli, as well as the mutant LR-192G and their B subunits (CTB and LTB) have been shown to increase immune responses against unrelated co-administered antigens by mucosal routes. However, their mechanism of action is very complex and not completely understood and differences exist between holotoxins and B subunits and within molecules, differences exist between the models used.In this work, we have studied the effects of these five molecules on antibody responses and on CD4+ T cell responses in a murine model of intrarectal immunization using rotavirus-like particles (2/6-VLP). In non-immunized mice, we have shown that all molecules, except CTB, decreased CD4+CD25+Foxp3+ natural regulatory T cells, probably by induction of apoptosis.In immunized mice, all molecules induced similar VLP-2/6 specific systemic and fecal antibody responses, teither he holotoxins, which are well known for their strong adjuvanticity or their B subunits with a less strong adjuvanticity but with also a tolerogenic effect in some studies.Regarding the CD4+ T cell response, antigen- and adjuvant- specific responses have been analysed. Important differences have been highlighted between the molecules. Among others things, only whole toxins (LT, LT-R192G and CT) trigger IL-2 production and activation of antigen specific memory CD4+CD25+Foxp3- T cells and at the same time antigen specific CD4+CD25+Foxp3+ regulatory T cells are activated which may control the effector response (Feedback loop regulation) and avoid deleterious inflammation. In spite of these differences, all studied molecules triggered IL-17 production, suggesting the major role of this cytokine in adjuvanticity. We are currently comparing the intrarectal and intranasl routes in order to evaluate the role played by the route of immunisation in different effects of these molecules

Intimina é uma adesina de natureza protéica das bactérias diarreiogênicas Escherichia coli enteropatogenica (EPEC) e enterohemorrágica (EHEC), capazes de induzir a lesão \'attaching e effacing\' em enterócitos. Os principais subtipos de intiminas de EPEC e EHEC prevalentes no Brasil são α, β e γ. Nosso objetivo foi investigar a transferência de anticorpos maternos anti-intiminas aos recém-nascidos de mães saudáveis de São Paulo, Brasil. Foram pesquisados anticorpos SIgA no colostro e IgG no soro de 50 mulheres saudáveis e no soro de cordão umbilical de seus recém-nascidos, por ELISA utilizando como antígeno proteínas recombinantes purificadas das regiões conservadas e variáveis de intiminas α, β e γ. As concentrações de anticorpos no colostro foram superiores quando comparadas com as concentrações do soro para todos os tipos de intiminas. Não se observaram diferenças estatísticas entre as concentrações de anticorpos reativos com as diferentes intiminas nas amostras de colostro. As concentrações de anticorpos reativos com a região conservada da intimina foram significativamente mais elevadas em comparação com as regiões variáveis no soro dos grupos de mães e de recém-nascidos. Houve alta correlação entre todos os anticorpos anti-intiminas nas amostras de colostro. Comparando-se as concentrações de anticorpos séricos, os coeficientes foram maiores entre anti-α e anti-β que entre os outros pares. Nossos resultados confirmam a transferência de anticorpos maternos para o recém-nascido pela placenta e pelo aleitamento materno e reforça o efeito protetor da amamentação contra infecção por EPEC. / Intimin is a proteic adhesin of enteropatogenic (EPEC) and enterohemorragic (EHEC) Escherichia coli, capable of inducing attachment and effacement lesion in enterocytes. The main subtypes of intimins of EPEC and EHEC prevalent in Brazil are α, β and γ. Our aim is to investigate the transference of maternal anti-intimin antibodies to the newborns of healthy mothers from Sao Paulo, Brazil. IgG and SIgA antibodies were determined in sera and colostrum from 50 healthy women and cord sera from their newborns, by ELISA using as antigens purified recombinant proteins, conserved and variable regions of α, β and γ intimins. The IgA antibody concentrations of colostrum are higher than IgG antibodies in serum for all intimins and there were no statistical differences between them in colostrum samples. The concentrations of antibodies reactive with the conserved region of intimin are significantly higher compared to the variable regions in the sera groups, mothers and newborns. There were high correlation coefficients between all the anti-intimins antibodies in colostrum samples. In the comparison of the seric antibody concentrations, the coefficients were higher between anti-α and anti-β than all the other pairs. Our results confirm the transference of maternal antibodies to the newborns by placenta and breastfeeding and reinforce the high protection effect of breastfeeding against EPEC infection.

Gedächtnis-B-Zellen und Plasmazellen sind essentielle Komponenten der protektiven Immunität. Die Mechanismen ihrer Induktion, ihres Überlebens und der Gedächtnis-B-Zellreaktivierung sind allerding bisher nur unvollständig verstanden. Um unser Wissen diesbezüglich zu erweitern, wurden in der vorliegenden Arbeit zum einen Charakteristika von Primär- und Sekundärimmunantworten nach Immunisierung mit Keyhole Limpet Hemocyanin (KLH) untersucht und zum anderen das Vorkommen sowie der Phänotyp humaner Gedächtnis-B-Zellen in verschiedenen lymphatischen Geweben analysiert. Die primäre parenterale KLH Immunisierung führte auf serologischer und zellulärer Ebene zu einer Reihe unerwarteter Ergebnisse, welche u. a. das Auftreten von IgA Antikörpern und die gleichzeitige Präsenz von hoch- und wenig mutierten primären Plasmablasten beinhalteten. Die Untersuchung der Gedächtnis-B-Zellverteilung in verschiedenen lymphatischen Geweben ergab den größten Gedächtnis-B-Zellpool in der Milz. Blut-, Tonsillen-, Knochenmarks- und Milz-Gedächtnis-B-Zellen wiesen nur wenige phänotypische Unterschiede auf. Einer davon war die CD69 Expression auf tonsillären ruhenden Gedächtnis-B-Zellen, was darauf hindeutet, dass tonsilläre Gedächtnis-B-Zellen tatsächlich sessil sein könnten. Die hier erhaltenen Ergebnisse stellen neue Erkenntnisse über bisher unbeschriebene Mechanismen bei parenteralen Immunantworten wie zum Beispiel die Induktion von IgA Antikörpern sowie die potentielle Rekrutierung kreuzreaktiver Gedächtnis-B-Zellen dar. Es bleibt zu klären, wie die Reaktivierung solcher Gedächtnis-B-Zellen reguliert ist. Derartiges Wissen wäre insbesondere für Therapien von Erkrankungen des Immunsystems, wie Autoimmunität, von Bedeutung. Das potentiell patrouillierende Verhalten der Gedächtnis-B-Zellen ist ein markanter Unterschied zu den nischenabhängigen sessilen Plasmazellen und deutet weitestgehend darauf hin, dass Gedächtnis-B-Zellen nicht auf derartige Nischen angewiesen sind. / Memory B cells (mBC) and antibodies are major mediators of protective immune responses yet the mechanisms of their induction, maintenance and mBC reactivation are poorly understood. Therefore, to enhance knowledge in this regard this study comprehensively characterized a human primary and secondary B cell immune response to Keyhole Limpet Hemocyanin (KLH). Secondly, mBC maintenance was investigated by a systematic analysis of mBC presence, frequency and phenotype within different lymphoid organs. Parenteral primary KLH immunization yielded unexpected results on the serological and B cellular level, including KLH-specific IgA antibody induction, the simultaneous presence of low and highly mutated circulating KLH-specific primary plasmablasts and only little clonal overlap between the primary, memory and secondary KLH-specific B cell repertoires. With respect to the organ distribution of human mBC, the spleen was identified as a major mBC reservoir. Splenic, tonsillar, bone marrow and blood mBC pools exhibited a largely comparable phenotype. Yet, we found tonsillar mBC to express CD69. Due to their resting state tonsillar mBC could therefore constitute a tissue resident cell population. The observations described allow insights into hitherto unknown potential mechanisms behind primary immune responses, i.e. prominent IgA induction by parenteral challenge and inclusion of cross-reactive mBC. The so far unclear regulatory players involved deserve future investigation, as such knowledge may be crucial for therapeutic interventions in immune system disorders. Furthermore, strikingly different to the resident plasma cells in the bone marrow, mBC appear to distribute between lymphoid organs and continuously recirculate in peripheral blood indicative of their potential permanent screening activities, suggesting that human mBC do not require one dedicated niche for their principle survival.

Abordagens atuais no desenho de vacinas contra o HIV-1 estão focadas em imunógenos que codificam proteínas inteiras do HIV-1 e visam induzir respostas citotóxicas específicas. É concebível que vacinas bem-sucedidas devem induzir respostas contra múltiplos epitopos do HIV-1, coincidindo com seqüências das cepas circulantes do vírus, conhecido por sua grande variabilidade genética. Sabe-se que células T CD4+ são necessárias para indução de respostas efetivas de linfócitos T CD8+ citotóxicos. Neste trabalho, nós avaliamos a imunogenicidade de uma vacina de DNA codificando 18 epitopos para linfócitos T CD4+, conservados e ligadores de múltiplas moléculas HLA-DR em camundongos BALB/c e em quatro linhagens de camundongos transgênicos para moléculas de HLA classe II. Os camundongos imunizados apresentaram respostas de amplitude e magnitude significativas com proliferação e secreção de citocinas por linfócitos T CD4+ e T CD8+. Onze dos 18 epitopos para linfócitos T CD4+ presentes na vacina foram reconhecidos pelas linhagens de camundongos transgênicos para moléculas de HLA classe II. Em suma, 17 dos 18 epitopos codificados pela vacina foram reconhecidos. As células induzidas pela vacina apresentaram um perfil polifuncional com tipo 1 de citocinas, incluindo produção de IFN- , TNF- e IL-2. A vacina também induziu células T CD4+ de memória central de longa duração, capazes de fornecer auxílio contínuo para células T CD8 +. Pela capacidade da vacina HIVBr18 de induzir respostas contra múltiplos epitopos de linfócitos T CD4+ conservados que podem ser reconhecidos no contexto de múltiplas moléculas de HLA classe II, esse conceito vacinal pode solucionar o problema da variabilidade genética viral assim como aumentar a cobertura populacional. Portanto, essa vacina, pode ser útil se utilizada isoladamente ou como fonte de auxílio cognato para células T CD8+ HIV-específicas induzidas por outros imunógenos gerando resposta em uma grande proporção dos vacinados / Current HIV vaccine approaches are focused on immunogens encoding whole HIV antigenic proteins that elicit cytotoxic CD8+ responses. It is conceivable that successful vaccines have to elicit responses to multiple epitopes, to match circulating strains of HIV, a virus known for its high genetic variability. It is known that CD4+ T cell responses are necessary for effective CD8+ antiviral responses. Here we assessed the immunogenicity of a DNA vaccine encoding 18 conserved, multiple HLA-DR-binding HIV CD4 epitopes in BALB/c and four strains of HLA class II-transgenic mice. Immunized mice displayed CD4+ and CD8+ proliferative and cytokine T cell responses of significant breadth and magnitude. Eleven out of the 18 encoded epitopes were recognized by CD4+ T cells from HLA class IItransgenic strain. Overall, 17 out of the 18 encoded peptides were recognized. The induced T cell response had a polyfunctional type 1 cytokine profile, including IFN- , TNF- and IL-2. The vaccine also induced long-lived central memory CD4+ T cells, which might provide sustained help for CD8+ T cells. By virtue of inducing broad responses against conserved CD4+ T cell epitopes that can be recognized in the context of widely diverse, common HLA class II alleles, this vaccine concept may cope both with HIV genetic variability and increased population coverage. The vaccine may thus be usefull either as a standalone approach or as a source of cognate help for HIV-specific CD8+ T cells elicited by conventional immunogens, eliciting responses in a wide proportion of vaccinees

Pacientes infectados pelo HIV apresentam resposta de imunogenicidade menor àquela obtida pela população geral com a imunização de rotina. A vacina meningocócica C conjugada é indicada para essa população, não existindo pesquisas prévias que avaliassem a imunogenicidade desta, para esse grupo específico. O estudo realizou essa avaliação comparando a resposta vacinal entre os pacientes infectados e não infectados pelo HIV, as relações dessa resposta com parâmetros clínicos e laboratoriais da infecção pelo vírus e os eventos adversos à vacinação. Utilizou-se as técnicas ensaios de anticorpos bactericidas séricos ou ação bactericida no soro (SBA) e o enzyme-linked immunosorbent assay (ELISA). Tratou-se de um ensaio clínico, envolvendo 92 pacientes, com idades entre 10-20 anos, sendo 43 infectados e 49 não infectados pelo HIV. Após a vacinação, 72,1% do grupo HIV+ e 100% do grupo HIV- foram considerados protegidos. Os pacientes do grupo HIV+ não respondedores à vacinação foram revacinados, tendo sido respondedores a essa nova dose 40% destes. Portanto, 81,4% dos pacientes infectados pelo HIV adquiriram proteção com a vacina (após uma ou duas doses). Foi encontrada correlação da resposta vacinal com o número de esquemas antirretrovirais previamente utilizados e carga viral pré-vacinação, não havendo outras associações com os demais parâmetros clínicos e laboratoriais da infecção pelo HIV. Pacientes com adequada resposta vacinal tenderam a ser os de menor idade. Efeitos colaterais ocorreram em 16,3% no grupo HIV+ e em 44% no HIV-. Conclui-se que a vacina meningocócica C conjugada é segura e efetiva para uso em adolescentes e adultos jovens com aids, embora a resposta de anticorpos seja menor do que a observada em indivíduos saudáveis. Isso indica a necessidade de discussão de novos esquemas de imunização em infectados pelo HIV, objetivando uma proteção mais efetiva contra doença meningocócica / Children and adolescents infected with HIV typically have a weaker response to immunization in comparison with the healthy population. The meningococcal C conjugate vaccine is routinely recommended for those individuals. No studies, however, have evaluated the antibody response to this vaccine in HIV-infected patients yet. In this study, we compared the antibody response to the meningococcal C conjugate vaccine between HIV-infected and HIV-uninfected patients using the serum bactericidal antibody assay (SBA) and the enzyme-linked immunoabsorbent assay (ELISA). Additional objectives were to determine whether the acquired immunity correlated with clinical and laboratory features of HIV infection, and to evaluate the vaccine side effects in this population. This clinical trial included 92 patients aged 10 to 20 years old: 43 HIV-infected and 49 HIV-uninfected patients. After one single dose of the vaccine, 72.1% of the HIV-infected and 100% of the HIV-uninfected patients were considered protected. Of the HIV-infected patients (non-responders in first dose) who received a second dose of the vaccine, only 40% reached protective antibody levels. Overall, 81.4% of the HIV-infected patients reached protective antibody titres (after one or two doses of the vaccine). The antibody response in HIV-infected patients correlated with the number of prior antiretroviral therapy schedules and with the pre-vaccination viral load, but with no other clinical features or laboratory tests. Patients with adequate vaccinal response tended to be younger. Side effects occurred in 16.3% and 44% of the HIV-infected and HIV-uninfected groups, respectively. In conclusion, the meningococcal serogroup C conjugate vaccine proved to be safe and effective in HIV-infected adolescents and young adults, although their antibody response was weaker than that of HIV-uninfected patients. These results suggest that the immunization schedule for HIV-infected patients should be re-evaluated, in order to assure more effective protection against the meningococcal disease in this population

A imunização materna com a vacina acelular para pertussis (dTpa) é uma intervenção adicional que visa fornecer proteção aos recém-nascidos (RN). No entanto, tem sido relatado que altos níveis de anticorpos adquiridos por transferência placentária podem afetar adversamente a resposta imune desses RN após a imunização ativa, devido ao mascaramento antigênico. Neste estudo, avaliamos a aquisição passiva neonatal de anticorpos específicos para pertussis e sua influência na resposta imune celular dos neonatos. A casuística foi composta por gestantes vacinadas com a vacina dTpa (grupo caso, n=66) ou por gestantes que não receberam a vacina (grupo controle, n=101). As concentrações de anticorpos IgG séricos específicos para Bordetella pertussis total (Bp), toxina pertussis (PT), hemaglutinina filamentosa (FHA) e pertactina (PRN) foram quantificadas em soro materno e de cordão umbilical de seu respectivo RN, e as concentrações de anticorpos IgA específicos para Bp e PT foram dosadas nas amostras de colostro por meio de ensaio imunoenzimático. A responsividade dos linfócitos do sangue neonatal foi avaliada após estimulação ex vivo com Bp inativada por citometria de fluxo com o intuito de detectar a proliferação, produção de citocinas e fenótipo de ativação dos linfócitos T em um contexto de altas concentrações de IgG específicas adquiridas após a vacinação materna. As concentrações de anticorpos IgG anti-Bp, PT, FHA e PRN foram maiores nas amostras de soro materno e de cordão umbilical do grupo caso quando comparadas ao grupo controle (p < 0,0001), com índices de correlação positivos em ambos os grupos para todos os antígenos estudados (p < 0,0001). As vacinações realizadas entre 26 e 31 semanas de gestação foram associadas com as melhores taxas de transferência placentária, embora índices significativamente menores foram detectados no grupo caso (p < 0,01). As concentrações de anticorpos IgA anti-Bp e anti-PT no colostro não foram afetadas pelo estado vacinal da parturiente. Os ensaios de cultura celular revelaram que os RN responderam ao estímulo com Bp, com maior expressão de CD40L, CD69 e proliferação de células T CD4, em comparação com células não estimuladas. Também foi observada uma menor resposta Th1, enquanto a resposta Th2 foi preservada, em comparação com os adultos, mas sem diferenças entre os grupos de neonatos em nenhum dos parâmetros estudados. Nossos resultados indicam que níveis mais altos de anticorpos IgG específicos para B. pertussis no soro dos RN após a vacinação materna não afetam a resposta imune neonatal mediada por células / Maternal immunization with pertussis acellular vaccine (Tdap) is an additional intervention that provides protection to newborns. However, it has been reported that high antibody levels acquired via placental transfer may adversely affect the immune response of newborns after active immunization due to epitope masking. In this study, we evaluated neonatal passive acquisition of pertussis-specific antibodies and their influence on the neonatal cell-mediated immune response. The sample consisted of pregnant women vaccinated with the Tdap vaccine (case group, n=66) or pregnant women who received no vaccine (control group n=101). Whole-cell Bordetella pertussis (Bp), pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (PRN)-specific serum IgG concentrations were quantified in paired maternal-cord sera, and Bp- and PT-specific IgA concentrations were evaluated in colostrum samples by immunoenzymatic assay. Ex vivo neonatal blood lymphocyte responsiveness after inactivated Bp stimulation was assessed using flow cytometry to detect the proliferation, cytokine production and activation phenotype of T lymphocytes in the context of high specific IgG concentrations acquired after maternal vaccination. Anti-Bp, PT, FHA and PRN IgG antibody concentrations in maternal and cord serum samples from case group were higher than those in control group (p < 0.0001), with positive correlation indexes in both groups for all pertussis antigens (p < 0.0001). Vaccinations performed between 26 and 31 gestation weeks were associated with the best placental transfer ratios, although significantly lower ratios were detected in case group (p < 0.01). Anti-Bp and anti-PT IgA concentrations in colostrum were not affected by vaccine status. Cell culture assays revealed that newborns responded to Bp stimulation with higher expression of CD40L CD69 and CD4+ T cell proliferation compared to unstimulated cells. It was also observed a lower Th1 response, while a preserved Th2 response compared to adults, but there were no differences between neonatal groups for any of the studied parameters. Our results indicate that higher pertussis-specific IgG levels in newborn sera after maternal vaccination do not affect the neonatal cell-mediated immune response