Impacto de poblaciones celulares efectoras y entorno de activación en la respuesta protectora contra pertussis

Pertussis es una patología respiratoria causada por la bacteria B. pertussis que es considerada la enfermedad inmunoprevenible menos controlada. El grupo de investigación al que pertenezco ha desarrollado una nueva formulación vacunal basada en vesículas de membrana externa (OMVs) derivadas de B. pertussis, que ha resultado protectora y segura en el modelo murino de infección intranasal. Objetivo: Obtener y poner a punto herramientas necesarias para identificar y caracterizar el rol de la población celular CD4 en el contexto de la inmunización contra pertussis utilizando el modelo murino de protección, a corto y largo plazo. Metodología: Trabajamos de forma comparativa con las vacunas comerciales en uso. Los ensayos se realizaron en una situación de protección a corto y largo plazo empleando el modelo de desafío intranasal en ratones. Evaluamos la capacidad protectora de la inmunidad celular de esplenocitos provenientes de animales inmunizados y luego depletados con MoAb anti mouse CD4 (ascitis de hibridoma GK1.5). Resultados: El tratamiento i.p. con el MoAb anti CD4 en los ratones dadores y receptores de esplenocitos puso de manifiesto el rol de las células CD4 en la protección celular inducida por las OMVs cuando la transferencia fue de 4,2x107 esplenocitos. En el corto plazo, la transferencia de esplenocitos provenientes de animales inmunizados con OMVBp redujo la colonización bacteriana de los pulmones: 4,99±0,15 vs. 5,99±0,15 logCFU/pulmones (p<0,005). La depleción de células CD4 produjo un incremento significativo en el recuento: 5,99±0,061 logCFU/pulmones (p<0,05). Este efecto no pudo observarse en el largo plazo aunque la inmunización activa a ese tiempo es efectiva. El análisis de los resultados sugiere que la respuesta de memoria residente en tejido (pulmón) podría tener un rol clave en la protección a largo plazoFil: Elizagaray, Maia L.. Universidad Nacional de La PlataFil: Hozbor, Daniela F.. Universidad Nacional de La PlataFil: Moreno, Griselda N.. Universidad Nacional de La PlataFil: Rumbo, Martín. Universidad Nacional de La Plat

Highlights of the 11th International Bordetella Symposium: From basic biology to vaccine development

Pertussis is a severe respiratory disease caused by infection with the bacterial pathogen Bordetella pertussis. The disease affects individuals of all ages but is particularly severe and sometimes fatal in unvaccinated young infants. Other Bordetella species cause diseases in humans, animals, and birds. Scientific, clinical, public health, vaccine company, and regulatory agency experts on these pathogens and diseases gathered in Buenos Aires, Argentina from 5 to 8 April 2016 for the 11th International Bordetella Symposium to discuss recent advances in our understanding of the biology of these organisms, the diseases they cause, and the development of new vaccines and other strategies to prevent these diseases. Highlights of the meeting included pertussis epidemiology in developing nations, genomic analysis of Bordetella biology and evolution, regulation of virulence factor expression, new model systems to study Bordetella biology and disease, effects of different vaccines on immune responses, maternal immunization as a strategy to prevent newborn disease, and novel vaccine development for pertussis. In addition, the group approved the formation of an International Bordetella Society to promote research and information exchange on bordetellae and to organize future meetings. A new Bordetella.org website will also be developed to facilitate these goals.Instituto de Biotecnologia y Biologia Molecula

Highlights of the 11th International Bordetella Symposium: From basic biology to vaccine development

Pertussis is a severe respiratory disease caused by infection with the bacterial pathogen Bordetella pertussis. The disease affects individuals of all ages but is particularly severe and sometimes fatal in unvaccinated young infants. Other Bordetella species cause diseases in humans, animals, and birds. Scientific, clinical, public health, vaccine company, and regulatory agency experts on these pathogens and diseases gathered in Buenos Aires, Argentina from 5 to 8 April 2016 for the 11th International Bordetella Symposium to discuss recent advances in our understanding of the biology of these organisms, the diseases they cause, and the development of new vaccines and other strategies to prevent these diseases. Highlights of the meeting included pertussis epidemiology in developing nations, genomic analysis of Bordetella biology and evolution, regulation of virulence factor expression, new model systems to study Bordetella biology and disease, effects of different vaccines on immune responses, maternal immunization as a strategy to prevent newborn disease, and novel vaccine development for pertussis. In addition, the group approved the formation of an International Bordetella Society to promote research and information exchange on bordetellae and to organize future meetings. A new Bordetella.org website will also be developed to facilitate these goals.Instituto de Biotecnologia y Biologia Molecula

Epidemiological situation of pertussis and strategies to control it. Argentina, 2002-2011

Fil: Romanin, Viviana. Programa Nacional de Control de Enfermedades Inmunoprevenibles (ProNaCEI), Ministerio de Salud de la Nación; Argentina.Fil: Agustinho, Vanina. Programa Nacional de Control de Enfermedades Inmunoprevenibles (ProNaCEI), Ministerio de Salud de la Nación; Argentina.Fil: Califano, Gloria. Programa Nacional de Control de Enfermedades Inmunoprevenibles (ProNaCEI), Ministerio de Salud de la Nación; Argentina.Fil: Sagradini, Sandra. Programa Nacional de Control de Enfermedades Inmunoprevenibles (ProNaCEI), Ministerio de Salud de la Nación; Argentina.Fil: Aquino, Analia. Programa Nacional de Control de Enfermedades Inmunoprevenibles (ProNaCEI), Ministerio de Salud de la Nación; Argentina.Fil: Juarez, María del Valle. Programa Nacional de Control de Enfermedades Inmunoprevenibles (ProNaCEI), Ministerio de Salud de la Nación; Argentina.Fil: Antman, Julián. Dirección de Epidemiología, Ministerio de Salud de la Nación; Argentina.Fil: Giovacchini, Carlos. Dirección de Epidemiología, Ministerio de Salud de la Nación; Argentina.Fil: Galas, Marcelo F. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Lara, Claudia. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Hozbor, Daniela. . Laboratorio Nacional de Referencia Coqueluche, VacSal, Instituto de Biotecnología y Biología Molecular. Facultad de Ciencias Exactas. Universidad Nacional de La Plata; Argentina.Fil: Gentile, Ángela. Sociedad Argentina de Pediatría; Argentina.Fil: Vizzotti, Carla. Programa Nacional de Control de Enfermedades Inmunoprevenibles (ProNaCEI), Ministerio de Salud de la Nación; Argentina.Coqueluche constituye un problema de salud pública. Objetivos: Describir la morbimortalidad y coberturas de vacunación entre 2002 y 2011, el perfil de los casos de 2011 y las estrategias de control implementadas por el Ministerio de Salud (MSN)

Highlights of the 12th International Bordetella Symposium

To commemorate the 100th anniversary of the Nobel prize being awarded to Jules Bordet, the discoverer of Bordetella pertussis, the 12th International Bordetella Symposium was held from 9 to 12 April 2019 at the Universite Libre de Bruxelles, where Jules Bordet studied and was Professor of Microbiology. The symposium attracted more than 300 Bordetella experts from 34 countries. They discussed the latest epidemiologic data and clinical aspects of pertussis, Bordetella biology and pathogenesis, immunology and vaccine development, and genomics and evolution. Advanced technological and methodological tools provided novel insights into the genomic diversity of Bordetella and a better understanding of pertussis disease and vaccine performance. New molecular approaches revealed previously unrecognized complexity of virulence gene regulation. Innovative insights into the immune responses to infection by Bordetella resulted in the development of new vaccine candidates. Such discoveries will aid in the design of more effective approaches to control pertussis and other Bordetella-related diseases.Instituto de Biotecnologia y Biologia MolecularCentro de Investigación y Desarrollo en Fermentaciones Industriale

Highlights of the 11th International Bordetella Symposium: From basic biology to vaccine development

Pertussis is a severe respiratory disease caused by infection with the bacterial pathogen Bordetella pertussis. The disease affects individuals of all ages but is particularly severe and sometimes fatal in unvaccinated young infants. Other Bordetella species cause diseases in humans, animals, and birds. Scientific, clinical, public health, vaccine company, and regulatory agency experts on these pathogens and diseases gathered in Buenos Aires, Argentina from 5 to 8 April 2016 for the 11th International Bordetella Symposium to discuss recent advances in our understanding of the biology of these organisms, the diseases they cause, and the development of new vaccines and other strategies to prevent these diseases. Highlights of the meeting included pertussis epidemiology in developing nations, genomic analysis of Bordetella biology and evolution, regulation of virulence factor expression, new model systems to study Bordetella biology and disease, effects of different vaccines on immune responses, maternal immunization as a strategy to prevent newborn disease, and novel vaccine development for pertussis. In addition, the group approved the formation of an International Bordetella Society to promote research and information exchange on bordetellae and to organize future meetings. A new Bordetella.org website will also be developed to facilitate these goals.Instituto de Biotecnologia y Biologia Molecula

Prevalence of Pertussis Antibodies in Maternal Blood, Cord Serum, and Infants From Mothers With and Those Without Tdap Booster Vaccination During Pregnancy in Argentina

Fil: Fallo, Aurelia A. Department of Pediatric Infectious Diseases, School of Medicine, Hospital de Niños "Ricardo Gutiérrez," University of Buenos Aires; Argentina.Fil: Neyro, Silvina E. Department of Pediatric Infectious Diseases, School of Medicine, Hospital de Niños "Ricardo Gutiérrez," University of Buenos Aires; Argentina.Fil: Manonelles, Gabriela V. Department of Pediatric Infectious Diseases, School of Medicine, Hospital de Niños "Ricardo Gutiérrez," University of Buenos Aires; Argentina.Fil: Lara, Claudia. Administración Nacional de Laboratorios e Institutos de Salud “Dr. Carlos G. Malbrán” (ANLIS); Argentina.Fil: Hozbor, Daniela. Laboratorio VacSal, Instituto de Biotecnología y Biología Molecular (IBBM), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, CCT-CONICET; Argentina.Fil: Zintgraff, Jonathan. Administración Nacional de Laboratorios e Institutos de Salud “Dr. Carlos G. Malbrán” (ANLIS); Argentina.Fil: Mazzeo, Silvina. Departments of Obstetrics and Gynecology, Hospital D. F. Santojanni, Buenos Aires; Argentina.Fil: Davison, Héctor E. Departments of Obstetrics and Gynecology, Hospital D. F. Santojanni, Buenos Aires; Argentina.Fil: González, Susana. Pediatrics, Hospital D. F. Santojanni, Buenos Aires; Argentina.Fil: Zapulla, Estella. Pediatrics, Hospital D. F. Santojanni, Buenos Aires; ArgentinaFil: Canle, Oscar. Blood Center, Hospital de Niños "Ricardo Gutiérrez," Buenos Aires; ArgentinaFil: Huespe, Miguel. Departments of Obstetrics and Gynecology, Hospital D. F. Santojanni, Buenos Aires; Argentina.Fil: Galas, Marcelo. Administración Nacional de Laboratorios e Institutos de Salud “Dr. Carlos G. Malbrán” (ANLIS); Argentina.Fil: López, Eduardo L. Department of Pediatric Infectious Diseases, School of Medicine, Hospital de Niños "Ricardo Gutiérrez," University of Buenos Aires; Argentina.Morbidity and mortality rates for pertussis in infants are high because disease often occurs before the onset of routine immunization or in those who do not complete a primary immunization series. Pertussis immunization is recommended during pregnancy to achieve antibody levels sufficient to protect young infants. To our knowledge, no previous reports of maternal pertussis immunization results in Latin America exist in the literature

Mucosal immunization with PspA (Pneumococcal surface protein A)-adsorbed nanoparticles targeting the lungs for protection against pneumococcal infection

Burden of pneumonia caused by Streptococcus pneumoniae remains high despite the availability of conjugate vaccines. Mucosal immunization targeting the lungs is an attractive alternative for the induction of local immune responses to improve protection against pneumonia. Our group had previously described the development of poly(glycerol adipate-co-ω-pentadecalactone) (PGA-co-PDL) polymeric nanoparticles (NPs) adsorbed with Pneumococcal surface protein A from clade 4 (PspA4Pro) within L-leucine microcarriers (nanocomposite microparticles-NCMPs) for mucosal delivery targeting the lungs (NP/NCMP PspA4Pro). NP/NCMP PspA4Pro was now used for immunization of mice. Inoculation of this formulation induced anti-PspA4Pro IgG antibodies in serum and lungs. Analysis of binding of serum IgG to intact bacteria showed efficient binding to bacteria expressing PspA from clades 3, 4 and 5 (family 2), but no binding to bacteria expressing PspA from clades 1 and 2 (family 1) was observed. Both mucosal immunization with NP/NCMP PspA4Pro and subcutaneous injection of the protein elicited partial protection against intranasal lethal pneumococcal challenge with a serotype 3 strain expressing PspA from clade 5 (PspA5). Although similar survival levels were observed for mucosal immunization with NP/NCMP PspA4Pro and subcutaneous immunization with purified protein, NP/NCMP PspA4Pro induced earlier control of the infection. Conversely, neither immunization with NP/NCMP PspA4Pro nor subcutaneous immunization with purified protein reduced bacterial burden in the lungs after challenge with a serotype 19F strain expressing PspA from clade 1 (PspA1). Mucosal immunization with NP/NCMP PspA4Pro targeting the lungs is thus able to induce local and systemic antibodies, conferring protection only against a strain expressing PspA from the homologous family 2

Comparative epidemiologic characteristics of pertussis in 10 Central and Eastern European countries, 2000-2013

Publisher Copyright: © 2016 Heininger et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.We undertook an epidemiological survey of the annual incidence of pertussis reported from 2000 to 2013 in ten Central and Eastern European countries to ascertain whether increased pertussis reports in some countries share common underlying drivers or whether there are specific features in each country. The annual incidence of pertussis in the participating countries was obtained from relevant government institutions and/or national surveillance systems. We reviewed the changes in the pertussis incidence rates in each country to explore differences and/or similarities between countries in relation to pertussis surveillance; case definitions for detection and confirmation of pertussis; incidence and number of cases of pertussis by year, overall and by age group; population by year, overall and by age group; pertussis immunization schedule and coverage, and switch from whole-cell pertussis vaccines (wP) to acellular pertussis vaccines (aP). There was heterogeneity in the reported annual incidence rates and trends observed across countries. Reported pertussis incidence rates varied considerably, ranging from 0.01 to 96 per 100,000 population, with the highest rates generally reported in Estonia and the lowest in Hungary and Serbia. The greatest burden appears for the most part in infants (<1 year) in Bulgaria, Hungary, Latvia, Romania, and Serbia, but not in the other participating countries where the burden may have shifted to older children, though surveillance of adults may be inappropriate. There was no consistent pattern associated with the switch from wP to aP vaccines on reported pertussis incidence rates. The heterogeneity in reported data may be related to a number of factors including surveillance system characteristics or capabilities, different case definitions, type of pertussis confirmation tests used, public awareness of the disease, as well as real differences in the magnitude of the disease, or a combination of these factors. Our study highlights the need to standardize pertussis detection and confirmation in surveillance programs across Europe, complemented with carefully-designed seroprevalence studies using the same protocols and methodologies.publishersversionPeer reviewe

Differential Expression of Alpha 4 Integrins on Effector Memory T Helper Cells during Bordetella Infections. Delayed Responses in Bordetella pertussis

Bordetella pertussis (B. pertussis) is the causative agent of whooping cough, a respiratory disease that is reemerging worldwide. Mechanisms of selective lymphocyte trafficking to the airways are likely to be critical in the immune response to this pathogen. We compared murine infection by B. pertussis, B. parapertussis, and a pertussis toxin-deleted B. pertussis mutant (BpΔPTX) to test the hypothesis that effector memory T-helper cells (emTh) display an altered pattern of trafficking receptor expression in B. pertussis infection due to a defect in imprinting. Increased cell recruitment to the lungs at 5 days post infection (p.i.) with B. parapertussis, and to a lesser extent with BpΔPTX, coincided with an increased frequency of circulating emTh cells expressing the mucosal-associated trafficking receptors α4β7 and α4β1 while a reduced population of these cells was observed in B. pertussis infection. These cells were highly evident in the blood and lungs in B. pertussis infection only at 25 days p.i. when B. parapertussis and BpΔPTX infections were resolved. Although at 5 days p.i., an equally high percentage of lung dendritic cells (DCs) from all infections expressed maturation markers, this expression persisted only in B. pertussis infection at 25 days p.i. Furthermore, at 5 days p.i with B. pertussis, lung DCs migration to draining lymph nodes may be compromised as evidenced by decreased frequency of CCR7+ DCs, inhibited CCR7-mediated in vitro migration, and fewer DCs in lung draining lymph nodes. Lastly, a reduced frequency of allogeneic CD4+ cells expressing α4β1 was detected following co-culture with lung DCs from B. pertussis-infected mice, suggesting a defect in DC imprinting in comparison to the other infection groups. The findings in this study suggest that B. pertussis may interfere with imprinting of lung-associated trafficking receptors on T lymphocytes leading to extended survival in the host and a prolonged course of disease