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Polymyxins as Novel and Safe Mucosal Adjuvants to Induce Humoral Immune Responses in Mice
There is currently an urgent need to develop safe and effective adjuvants for enhancing vaccine-induced antigen-specific immune responses. We demonstrate here that intranasal immunization with clinically used polypeptide antibiotics, polymyxin B (PMB) and colistin (CL), along with ovalbumin (OVA), i...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3623863/ https://www.ncbi.nlm.nih.gov/pubmed/23593492 http://dx.doi.org/10.1371/journal.pone.0061643 |
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author | Yoshino, Naoto Endo, Masahiro Kanno, Hiroyuki Matsukawa, Naomi Tsutsumi, Reiko Takeshita, Ryosuke Sato, Shigehiro |
author_facet | Yoshino, Naoto Endo, Masahiro Kanno, Hiroyuki Matsukawa, Naomi Tsutsumi, Reiko Takeshita, Ryosuke Sato, Shigehiro |
author_sort | Yoshino, Naoto |
collection | PubMed |
description | There is currently an urgent need to develop safe and effective adjuvants for enhancing vaccine-induced antigen-specific immune responses. We demonstrate here that intranasal immunization with clinically used polypeptide antibiotics, polymyxin B (PMB) and colistin (CL), along with ovalbumin (OVA), increases OVA-specific humoral immune responses in a dose-dependently manner at both mucosal and systemic compartments. Enhanced immunity by boosting was found to persist during 8 months of observation. Moreover, mice intranasally immunized with OVA plus various doses of PMB or CL showed neither inflammatory responses in the nasal cavity and olfactory bulbs nor renal damages, compared to those given OVA alone. These data suggest that polymyxins may serve as novel and safe mucosal adjuvants to induce humoral immune responses. The polymyxin adjuvanticity was found to be independent of endotoxins liberated by its bactericidal activity, as indicated by similar enhancing effects of PMB in lipopolysaccharide (LPS)-hyporesponsive and LPS-susceptible mice. However, despite the presence of preexisting anti-PMB antibodies, we observed no reduction in the adjuvant function of polymyxins when they were given intranasally. Furthermore, the titers of OVA-specific Abs in mice intranasally immunized with OVA plus PMB or CL were significantly higher than those in mice administered with polymyxin analogues, such as polymyxin B nonapeptide and colistin methanesulfonate. The levels of released β-hexosaminidase and histamine in mast cell culture supernatants stimulated by PMB or CL were also significantly higher than those stimulated by their analogues. These results suggest that both the hydrophobic carbon chain and hydrophilic cationic cyclic peptide contribute to the mucosal adjuvanticity of PMB and CL. |
format | Online Article Text |
id | pubmed-3623863 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-36238632013-04-16 Polymyxins as Novel and Safe Mucosal Adjuvants to Induce Humoral Immune Responses in Mice Yoshino, Naoto Endo, Masahiro Kanno, Hiroyuki Matsukawa, Naomi Tsutsumi, Reiko Takeshita, Ryosuke Sato, Shigehiro PLoS One Research Article There is currently an urgent need to develop safe and effective adjuvants for enhancing vaccine-induced antigen-specific immune responses. We demonstrate here that intranasal immunization with clinically used polypeptide antibiotics, polymyxin B (PMB) and colistin (CL), along with ovalbumin (OVA), increases OVA-specific humoral immune responses in a dose-dependently manner at both mucosal and systemic compartments. Enhanced immunity by boosting was found to persist during 8 months of observation. Moreover, mice intranasally immunized with OVA plus various doses of PMB or CL showed neither inflammatory responses in the nasal cavity and olfactory bulbs nor renal damages, compared to those given OVA alone. These data suggest that polymyxins may serve as novel and safe mucosal adjuvants to induce humoral immune responses. The polymyxin adjuvanticity was found to be independent of endotoxins liberated by its bactericidal activity, as indicated by similar enhancing effects of PMB in lipopolysaccharide (LPS)-hyporesponsive and LPS-susceptible mice. However, despite the presence of preexisting anti-PMB antibodies, we observed no reduction in the adjuvant function of polymyxins when they were given intranasally. Furthermore, the titers of OVA-specific Abs in mice intranasally immunized with OVA plus PMB or CL were significantly higher than those in mice administered with polymyxin analogues, such as polymyxin B nonapeptide and colistin methanesulfonate. The levels of released β-hexosaminidase and histamine in mast cell culture supernatants stimulated by PMB or CL were also significantly higher than those stimulated by their analogues. These results suggest that both the hydrophobic carbon chain and hydrophilic cationic cyclic peptide contribute to the mucosal adjuvanticity of PMB and CL. Public Library of Science 2013-04-11 /pmc/articles/PMC3623863/ /pubmed/23593492 http://dx.doi.org/10.1371/journal.pone.0061643 Text en © 2013 Yoshino et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited. |
spellingShingle | Research Article Yoshino, Naoto Endo, Masahiro Kanno, Hiroyuki Matsukawa, Naomi Tsutsumi, Reiko Takeshita, Ryosuke Sato, Shigehiro Polymyxins as Novel and Safe Mucosal Adjuvants to Induce Humoral Immune Responses in Mice |
title | Polymyxins as Novel and Safe Mucosal Adjuvants to Induce Humoral Immune Responses in Mice |
title_full | Polymyxins as Novel and Safe Mucosal Adjuvants to Induce Humoral Immune Responses in Mice |
title_fullStr | Polymyxins as Novel and Safe Mucosal Adjuvants to Induce Humoral Immune Responses in Mice |
title_full_unstemmed | Polymyxins as Novel and Safe Mucosal Adjuvants to Induce Humoral Immune Responses in Mice |
title_short | Polymyxins as Novel and Safe Mucosal Adjuvants to Induce Humoral Immune Responses in Mice |
title_sort | polymyxins as novel and safe mucosal adjuvants to induce humoral immune responses in mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3623863/ https://www.ncbi.nlm.nih.gov/pubmed/23593492 http://dx.doi.org/10.1371/journal.pone.0061643 |
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