Yaffa Mizrachi Nebenzahl
Ben Gurion University of the Negev, Israel
Title: Identification of novel S. pneumoniae candidate vaccine antigens and the nature of the immune response elicited by them
Biography
Biography: Yaffa Mizrachi Nebenzahl
Abstract
Mortality due to pneumococcal infections remains high worldwide, augmented by widespread antibiotic resistance in many pneumococcal strains. To identify protein antigens that could be involved in the development of protective immunity to S. pneumoniae, a pneumococcal cell wall protein-enriched extract was screened using 2-D gel electrophoresis and immunoblotting with either sera obtained longitudinally from children attending day-care centers or sera obtained from mice immunized with the pneumococcal cell wall protein extract. The identified proteins that share no- or low- homology to human proteins and which are conserved among different S. pneumoniae strains were tested for their ability to elicit protection against S. pneumoniae challenge in animal models. Moreover the nature of the elicited immune response was studied in mice. S. pneumoniae proteins PtsA, GtS, Nox, PsipB, FBA, TF and FtsZ were amplified from TIGR4 strain, cloned, expressed in E. coli and purified. Mice were immunized three times intra-nasally or subcutaneously with these proteins in presence of adjuvant and challenged two weeks later. Nasopharyngeal and lung colonization levels were quantified for 48 hours following bacterial challenge and survival was monitored daily for seven days. The cytokine profile elicited by rFBA was determined by multiplex ELISA. All seven proteins elicited protective immune responses in mice as determined by reduced nasopharyngeal and lung colonization, prolonged survival, and the ability of antibodies obtained from immunized mice to ex-vivo neutralize bacterial virulence for the intra-peritoneal challenge model. Moreover, rFBA elicits Th1, Th2 and Th17-type cytokines in mice. Taken together several antigenic and immunogenic protein with no or low homology to human proteins were identified and found to elicit protective immune response in the mouse model accompanied by Th1, Th2 and Th17 type of immune responses.
References:
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2. Elhaik Goldman S, Dotan D, Talias A, Lilo A, Azriel S, Malka I, Portnoi M, Ohayon A, Kafka D, Ellis R, Elkabets M, Porgador A, Levin D, Azhar A, Swiatlo E, Ling E, Feldman G, Tal M, Dagan R, Mizrachi Nebenzahl Y (2016) Streptococcus pneumoniae fructose 1, 6-bisphosphate aldolase, a protein vaccine candidate, elicits Th1/Th2/Th17-type cytokines in mice. Int J Mol Med 37:1127-1138.
3. Mizrachi Nebenzahl Y, Blau K, Kushnir T, Shagan M, Portnoi M, Cohen A, Azriel S, Malka I, Adawi A, Kafka K, Dotan D, Guterman G, Troib S, Fishilevich T, Gershoni, J M, Braiman A, Mitchell A M, Mitchell T J, Porat N, Goliand I, Chalifa Caspi V, Swiatlo E, Tal M, Ellis R, Elia N, Dagan R (2016). Streptococcus pneumoniae cell-wall-localized phosphoenolpyruvate protein phosphotransferase can function as an adhesin: Identification of its host target molecules and evaluation of its potential as a vaccine. PLoS ONE. 11:e0150320.
4. Elhaik Goldman S, Moshkovits I, Shemesh A, Filiba A, Tsirulsky Y, Voronov E, Shagan M, Benharroch D, Karo-Atar D, Dagan R, Munitz A, Mizrachi Nebenzahl Y (2016) Natural killer receptor 1 dampens the development of allergic eosinophilic airway inflammation. PLoS ONE. 11:e0160779.