Neisseria meningitidis serogroup B lipopolysaccharides induce a lower pro-inflammatory effect within the proteoliposome used in Cuban anti-meningococcal vaccines
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng spa |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.vacun.2018.09.003 http://hdl.handle.net/11449/188383 |
Resumo: | Neisseria meningitidis outer membrane vesicles or proteoliposomes (PLs) have been used as vaccines and adjuvants. Despite the presence of potentially toxic amounts of lipopolysaccharide (LPS), they have been shown to be safe, well tolerated, and immunogenic. This suggests that LPS-PL may have reduced LPS toxicity. In this study, it is shown that the ability of PL to induce pro-inflammatory cytokine production in human U937 histiocytic cell line is significantly lower than that of an equivalent concentration of purified LPS. This demonstrates that certain components or physical properties of PL reduce the pro-inflammatory activity of their endogenous LPS. To investigate the mechanisms responsible for this protective effect, PLs were fractionated and an assessment was made of the ability of the resulting fractions to induce inflammatory cytokine expression. Several individual PLs fractions were more potent inducers of pro-inflammatory cytokine production than the non-fractionated PLs. The majority of the pro-inflammatory activities appeared to be mediated by the presence of LPS in the fractions, as shown by the ability of an anti-CD14 antibody to block it. However, in two PL fractions, the production of IL-8, and to a lesser extent IL-6, was not inhibited by anti-CD14 treatment, indicating that pro-inflammatory components other than LPS could also be present in PL. Eight proteins present in the fractions were identified by n-terminal sequencing. The results of this study suggest that two of them, PorB, and in particular, the RmpM protein, may also contribute to the pro-inflammatory activity of N. meningitidis PL. These results could support the development of PLs as vaccine adjuvant. |
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Neisseria meningitidis serogroup B lipopolysaccharides induce a lower pro-inflammatory effect within the proteoliposome used in Cuban anti-meningococcal vaccinesLos lipopolisacáridos de Neisseria meningitidis serogrupo B inducen un reducido efecto proinflamatorio dentro del proteoliposoma usado en vacunas cubanas antimeningocócicasAdjuvantLPSNeisseria meningitidisPro-inflammatory cytokinesProteoliposomeNeisseria meningitidis outer membrane vesicles or proteoliposomes (PLs) have been used as vaccines and adjuvants. Despite the presence of potentially toxic amounts of lipopolysaccharide (LPS), they have been shown to be safe, well tolerated, and immunogenic. This suggests that LPS-PL may have reduced LPS toxicity. In this study, it is shown that the ability of PL to induce pro-inflammatory cytokine production in human U937 histiocytic cell line is significantly lower than that of an equivalent concentration of purified LPS. This demonstrates that certain components or physical properties of PL reduce the pro-inflammatory activity of their endogenous LPS. To investigate the mechanisms responsible for this protective effect, PLs were fractionated and an assessment was made of the ability of the resulting fractions to induce inflammatory cytokine expression. Several individual PLs fractions were more potent inducers of pro-inflammatory cytokine production than the non-fractionated PLs. The majority of the pro-inflammatory activities appeared to be mediated by the presence of LPS in the fractions, as shown by the ability of an anti-CD14 antibody to block it. However, in two PL fractions, the production of IL-8, and to a lesser extent IL-6, was not inhibited by anti-CD14 treatment, indicating that pro-inflammatory components other than LPS could also be present in PL. Eight proteins present in the fractions were identified by n-terminal sequencing. The results of this study suggest that two of them, PorB, and in particular, the RmpM protein, may also contribute to the pro-inflammatory activity of N. meningitidis PL. These results could support the development of PLs as vaccine adjuvant.Royal SocietyDepartment of Immunology University of Medical ScienceDepartment of Microbiology and Immunology University of Newcastle upon Tyne The Medical School, Framlington PlaceUniversity of Sheffield D Floor School of Medicine and Biomedical Sciences, Beech Hill RoadSão Paulo State University (UNESP) School of Pharmaceutical Sciences Department of Clinical AnalysisSão Paulo State University (UNESP) School of Pharmaceutical Sciences Department of Clinical AnalysisUniversity of Medical ScienceThe Medical SchoolSchool of Medicine and Biomedical SciencesUniversidade Estadual Paulista (Unesp)Pérez, O.Graham, S.Lastre, M.Ellis, C. D.Pupo, R. R.Tellez-Martínez, D. [UNESP]Batista-Duharte, A. [UNESP]2019-10-06T16:06:19Z2019-10-06T16:06:19Z2018-07-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article52-60http://dx.doi.org/10.1016/j.vacun.2018.09.003Vacunas, v. 19, n. 2, p. 52-60, 2018.1578-88571576-9887http://hdl.handle.net/11449/18838310.1016/j.vacun.2018.09.0032-s2.0-85056800881Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengspaVacunasinfo:eu-repo/semantics/openAccess2024-06-21T15:18:13Zoai:repositorio.unesp.br:11449/188383Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T14:06:07.839860Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Neisseria meningitidis serogroup B lipopolysaccharides induce a lower pro-inflammatory effect within the proteoliposome used in Cuban anti-meningococcal vaccines Los lipopolisacáridos de Neisseria meningitidis serogrupo B inducen un reducido efecto proinflamatorio dentro del proteoliposoma usado en vacunas cubanas antimeningocócicas |
title |
Neisseria meningitidis serogroup B lipopolysaccharides induce a lower pro-inflammatory effect within the proteoliposome used in Cuban anti-meningococcal vaccines |
spellingShingle |
Neisseria meningitidis serogroup B lipopolysaccharides induce a lower pro-inflammatory effect within the proteoliposome used in Cuban anti-meningococcal vaccines Pérez, O. Adjuvant LPS Neisseria meningitidis Pro-inflammatory cytokines Proteoliposome |
title_short |
Neisseria meningitidis serogroup B lipopolysaccharides induce a lower pro-inflammatory effect within the proteoliposome used in Cuban anti-meningococcal vaccines |
title_full |
Neisseria meningitidis serogroup B lipopolysaccharides induce a lower pro-inflammatory effect within the proteoliposome used in Cuban anti-meningococcal vaccines |
title_fullStr |
Neisseria meningitidis serogroup B lipopolysaccharides induce a lower pro-inflammatory effect within the proteoliposome used in Cuban anti-meningococcal vaccines |
title_full_unstemmed |
Neisseria meningitidis serogroup B lipopolysaccharides induce a lower pro-inflammatory effect within the proteoliposome used in Cuban anti-meningococcal vaccines |
title_sort |
Neisseria meningitidis serogroup B lipopolysaccharides induce a lower pro-inflammatory effect within the proteoliposome used in Cuban anti-meningococcal vaccines |
author |
Pérez, O. |
author_facet |
Pérez, O. Graham, S. Lastre, M. Ellis, C. D. Pupo, R. R. Tellez-Martínez, D. [UNESP] Batista-Duharte, A. [UNESP] |
author_role |
author |
author2 |
Graham, S. Lastre, M. Ellis, C. D. Pupo, R. R. Tellez-Martínez, D. [UNESP] Batista-Duharte, A. [UNESP] |
author2_role |
author author author author author author |
dc.contributor.none.fl_str_mv |
University of Medical Science The Medical School School of Medicine and Biomedical Sciences Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Pérez, O. Graham, S. Lastre, M. Ellis, C. D. Pupo, R. R. Tellez-Martínez, D. [UNESP] Batista-Duharte, A. [UNESP] |
dc.subject.por.fl_str_mv |
Adjuvant LPS Neisseria meningitidis Pro-inflammatory cytokines Proteoliposome |
topic |
Adjuvant LPS Neisseria meningitidis Pro-inflammatory cytokines Proteoliposome |
description |
Neisseria meningitidis outer membrane vesicles or proteoliposomes (PLs) have been used as vaccines and adjuvants. Despite the presence of potentially toxic amounts of lipopolysaccharide (LPS), they have been shown to be safe, well tolerated, and immunogenic. This suggests that LPS-PL may have reduced LPS toxicity. In this study, it is shown that the ability of PL to induce pro-inflammatory cytokine production in human U937 histiocytic cell line is significantly lower than that of an equivalent concentration of purified LPS. This demonstrates that certain components or physical properties of PL reduce the pro-inflammatory activity of their endogenous LPS. To investigate the mechanisms responsible for this protective effect, PLs were fractionated and an assessment was made of the ability of the resulting fractions to induce inflammatory cytokine expression. Several individual PLs fractions were more potent inducers of pro-inflammatory cytokine production than the non-fractionated PLs. The majority of the pro-inflammatory activities appeared to be mediated by the presence of LPS in the fractions, as shown by the ability of an anti-CD14 antibody to block it. However, in two PL fractions, the production of IL-8, and to a lesser extent IL-6, was not inhibited by anti-CD14 treatment, indicating that pro-inflammatory components other than LPS could also be present in PL. Eight proteins present in the fractions were identified by n-terminal sequencing. The results of this study suggest that two of them, PorB, and in particular, the RmpM protein, may also contribute to the pro-inflammatory activity of N. meningitidis PL. These results could support the development of PLs as vaccine adjuvant. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-07-01 2019-10-06T16:06:19Z 2019-10-06T16:06:19Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1016/j.vacun.2018.09.003 Vacunas, v. 19, n. 2, p. 52-60, 2018. 1578-8857 1576-9887 http://hdl.handle.net/11449/188383 10.1016/j.vacun.2018.09.003 2-s2.0-85056800881 |
url |
http://dx.doi.org/10.1016/j.vacun.2018.09.003 http://hdl.handle.net/11449/188383 |
identifier_str_mv |
Vacunas, v. 19, n. 2, p. 52-60, 2018. 1578-8857 1576-9887 10.1016/j.vacun.2018.09.003 2-s2.0-85056800881 |
dc.language.iso.fl_str_mv |
eng spa |
language |
eng spa |
dc.relation.none.fl_str_mv |
Vacunas |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
52-60 |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
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1808128316139372544 |