IBBM   21076
INSTITUTO DE BIOTECNOLOGIA Y BIOLOGIA MOLECULAR
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Evaluation of the memory immune response induced by the novel pertussis formulation based on outer membrane vesicles
Autor/es:
DANIELA HOZBOR; MIESZKO WILK; ALICJA MISIAK ; KINGSTON MILLS; MARIA EUGENIA ZURITA
Reunión:
Congreso; XII Congress of the Latin American Association of Immunology - ALAI XXIII Congress of the Mexican Society of Immunology - SMI; 2018
Resumen:
Pertussis is a respiratory disease caused by the Gram-negative bacteria Bordetellapertussis that despite being immune preventable remains one of the leading causes ofdeath in children under one year. In the last two decades, the incidence of this acuteinfectious respiratory disease has increased in many countries; with around 16 millioncases occurring per year associated with approximately 200,000 deaths [1]. Most ofthose cases have been reported in developing countries; although in recent years largeoutbreaks have also been detected in developed countries, even in those with highvaccination rates [1-3]. This epidemic detected in different countries has moved thescientific community and health professionals to seek an understanding of this alarmingnew situation, to identify the causes [2, 4, 5], and review and implement new strategiesfor the control of pertussis [6]. Several factors apparently contribute to this pertussiscase increase, probably some occurring at a different weight depending on the countryand the population considered. Nevertheless, a consensus exists in identifying, as partof the causes of the epidemic, several factors related to the vaccines currently in useand the vaccination?e. g. suboptimal coverage of the three primary doses,noncompliance with vaccination-schedule timing (delayed vaccination) [7, 8], thewaning of vaccination-conferred immunity [9-11], and the circulation of a resistantbacterial causative-agent population resulting from the selection pressure exerted bymass vaccination [5]. Currently two types of vaccines against pertussis are in use: thewhole-cell vaccines (wP) constituted by a suspension of detoxified heat-killed bacteriaand acellular vaccines (aP) consisting of purified B. pertussis immunogens. wP was thefirst developed against the disease. To improve the control strategies to the disease wehave developed a new vaccine candidate based on outer membrane vesicles (OMVs)capable of inducing a longer-term robust immune response [12-16].Recently it has been shown that the natural infection is capable of inducing a systemicimmune response with central memory T lymphocytes (TCM) and local memoryresponse with resident memory T cells (TRM). In the frame of the vaccination withwhole cell vaccine (wP) both populations are induced, while with the acellular vaccine(aP) the TRM population is absent. These results correlate with the reports that indicatethat the duration of the immunity conferred by aP is short. In order to evaluate theability of our vaccine candidate to induce TRM lymphocytes in the lung, in vivo assayswere performed in which the systemic and local response was evaluated, in comparisonwith the wP vaccine. We found that in the lungs of the group of animals immunizedwith OMVs, as occurred in wP immunized animals, TRM lymphocytes are induced(14.8×104 cells/lungs in both cases). These lymphocyte population is capable ofsecreting IFN-γ in response to specific stimuli: 8.49 ng/ml for OMVs immunizedanimals and 7.84 ng/ml for wP immunized animals. When we analyzed the systemicimmune response, we found that both formulations present a mixed profile withsecretion of IFN-γ [OMVs: 179.55 ng/ml; wP: 114.29 ng /ml] and IL-17 [OMVs: 1.84ng/ml; wP: 0.25 ng/ml]. The results obtained indicate that the immunization with aformulation based on OMVs is capable of inducing memory resident lymphocytepopulations in the lungs, which would explain the longer duration of the immunityinduced by this kind of formulation.(1) Anon. Pertussis vaccines: WHO position paper. Releve epidemiologiquehebdomadaire / Section d´hygiene du Secretariat de la Societe des Nations = Weeklyepidemiological record / Health Section of the Secretariat of the League of Nations 2010;85(40): 385-400.(2) He Q, Mertsola J. Factors contributing to pertussis resurgence. Future microbiology2008; 3(3): 329-339.(3) Clark TA. Changing pertussis epidemiology: everything old is new again. The Journalof infectious diseases 2014; 209(7): 978-981.(4) Jackson DW, Rohani P. Perplexities of pertussis: recent global epidemiological trendsand their potential causes. Epidemiology and infection 2014; 142(4): 672-684.(5) Bart MJ, et al. Global Population Structure and Evolution of Bordetella pertussis andTheir Relationship with Vaccination. mBio 2014; 5(2).(6) Forsyth K, et al. Strategies to Decrease Pertussis Transmission to Infants. Pediatrics2015.(7) Gentile A, et al. [Delayed vaccine schedule and missed opportunities for vaccinationin children up to 24 months. A multicenter study]. 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