CONICET | Buscador de Institutos y Recursos Humanos

INVESTIGADORES

HOZBOR Daniela Flavia

datos académicos

artículos

capítulos de libros

congresos y reuniones científicas

convenios, asesorías y/o servicios tecnológicos

informe técnico

congresos y reuniones científicas

Título:

Evaluation of the memory immune response induced by the novel pertussis formulation based on outer membrane vesicles

Autor/es:

ZURITA, MARÍA EUGENIA Y COLABORADORES IRLANDA; HOZBOR D

Reunión:

Congreso; - ALAI XXIII Congress of the Mexican Society of Immunology - SMI. MAY 14-18, 2018. CANCÚN .; 2018

Resumen:

Evaluationof the memory immune response induced by the novelpertussisformulation based on outer membrane vesiclesZurita, ME1;Mieszko, W2; Misiak, A2; Mills, K2; Hozbor, D11- Institutode Biotecnología y Biología molecular, UNLP-CONICET, Argentina2- School ofBiochemistry and Immunology, Trinity Biomedical Sciences Institute, Ireland Pertussis isa respiratory disease caused by the Gram-negative bacteria Bordetella pertussis that despite being immune preventable remainsone of the leading causes of death in children under one year. In the last twodecades, the incidence of this acute infectious respiratory disease hasincreased in many countries; with around 16 million cases occurring per yearassociated with approximately 200,000 deaths [1]. Most of those cases have been reported indeveloping countries; although in recent years large outbreaks have also beendetected in developed countries, even in those with high vaccination rates [1-3]. This epidemic detected in different countrieshas moved the scientific community and health professionals to seek anunderstanding of this alarming new situation, to identify the causes [2, 4, 5], and review and implement new strategies forthe control of pertussis [6]. Several factorsapparently contribute to this pertussis-case increase, probably some occurringat a different weight depending on the country and the population considered.Nevertheless, a consensus exists in identifying, as part of the causes of theepidemic, several factors related to the vaccines currently in use and thevaccination?e. g. suboptimal coverage of the three primary doses,noncompliance with vaccination-schedule timing (delayed vaccination) [7, 8], the waning of vaccination-conferred immunity [9-11], and the circulation of a resistant bacterialcausative-agent population resulting from the selection pressure exerted by mass vaccination [5]. Currently two types of vaccines againstpertussis are in use: the whole-cell vaccines (wP) constituted by a suspensionof detoxified heat-killed bacteria and acellular vaccines (aP) consisting ofpurified B. pertussis immunogens. wP was the first developed against thedisease. To improve the control strategies to the disease we have developed anew vaccine candidate based on outer membrane vesicles (OMVs) capable ofinducing a longer-term robust immune response [12-16].Recently ithas been shown that the natural infection is capable of inducing a systemicimmune response with central memory T-lymphocytes (TCM) and local memory Tcells with resident memory (TRM). In the frame of the vaccination with wholecell vaccine (wP) both populations are induced, while with the acellularvaccine (aP) the MRT population is absent. These results correlate with thereports that indicate that the duration of the immunity conferred by aP isshort. In order to evaluate the ability of our vaccine candidate to induce TRMlymphocytes in the lung, in vivo assays were performed in which the systemicand local response was evaluated, in comparison with the wP vaccine. We foundthat in the lungs of the group of animals immunized with OMVs, as occurred inwP immunized animals, TRM lymphocytes are induced (14.8 × 10 4 cells/lungs inboth cases). These lymphocyte population is capable of secreting IFN-γ inresponse to specific stimuli: 8.49ng/ml for OMVs immunized animals and 7.84ng/ml for wP immunized animals. When weanalyzed the systemic immune response, we found that both formulations presenta mixed profile with secretion of IFN-γ [OMVs: 179.55 ng / ml; wP: 114.29ng /ml] and IL-17 [OMVs: 1.84ng / ml; wP: 0.25ng / ml]. The results obtainedindicate that immunization with formulation based on OMVs is capable ofinducing memory resident lung lymphocyte populations, which would explain thelonger duration of the immunity induced by kind of formulation. (1) Anon. Pertussis vaccines: WHO positionpaper. Releve epidemiologiquehebdomadaire / Section d´hygiene du Secretariat de la Societe des Nations =Weekly epidemiological record / Health Section of the Secretariat of the Leagueof Nations 2010; 85(40):385-400.(2) He Q, Mertsola J. Factors contributingto pertussis resurgence. Futuremicrobiology 2008; 3(3):329-339.(3) Clark TA. Changing pertussisepidemiology: everything old is new again. TheJournal of infectious diseases 2014;209(7): 978-981.(4) Jackson DW, Rohani P. Perplexities ofpertussis: recent global epidemiological trends and their potential causes. Epidemiology and infection 2014; 142(4): 672-684.(5) Bart MJ, et al. Global PopulationStructure and Evolution of Bordetella pertussis and Their Relationship withVaccination. mBio 2014; 5(2).(6) Forsyth K, et al. Strategies toDecrease Pertussis Transmission to Infants. Pediatrics2015.(7) Gentile A, et al. [Delayed vaccineschedule and missed opportunities for vaccination in children up to 24 months.A multicenter study]. Archivos argentinosde pediatria 2011; 109(3):219-225.(8) Pesco P, et al. Mathematical modelingof delayed pertussis vaccination in infants. Vaccine 2015.(9) McGirr A, Fisman DN. Duration ofPertussis Immunity After DTaP Immunization: A Meta-analysis. Pediatrics 2015.(10) Klein NP, et al. Waning protectionafter fifth dose of acellular pertussis vaccine in children. The New England journal of medicine2012; 367(11): 1012-1019.(11) Wendelboe AM, et al. Duration ofimmunity against pertussis after natural infection or vaccination. The Pediatric infectious disease journal2005; 24(5 Suppl): S58-61.(12) Hozbor DF. Outer membrane vesicles: anattractive candidate for pertussis vaccines. Expert review of vaccines 2016: 1-4.(13) Asensio CJ, et al. Outer membranevesicles obtained from Bordetella pertussis Tohama expressing the lipid Adeacylase PagL as a novel acellular vaccine candidate. Vaccine 2011; 29(8):1649-1656.(14) Roberts R, et al. Outer membranevesicles as acellular vaccine against pertussis. Vaccine 2008; 26(36):4639-4646.(15) Bottero D, et al. Characterization ofthe immune response induced by pertussis OMVs-based vaccine. Vaccine 2016; 34(28): 3303-3309.(16) Gaillard ME, et al. Acellular pertussisvaccine based on outer membrane vesicles capable of conferring bothlong-lasting immunity and protection against different strain genotypes. Vaccine 2014; 32(8): 931-937.

enviar mensaje