Cargando…

Membrane-anchored CCL20 augments HIV Env-specific mucosal immune responses

BACKGROUND: Induction of broad immune responses at mucosal site remains a primary goal for most vaccines against mucosal pathogens. Abundance of evidence indicates that the co-delivery of mucosal adjuvants, including cytokines, is necessary to induce effective mucosal immunity. In the present study,...

Descripción completa

Detalles Bibliográficos
Autores principales: Sun, Xianliang, Zhang, Han, Xu, Shuiling, Shi, Lili, Dong, Jingjian, Gao, Dandan, Chen, Yan, Feng, Hao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5568278/
https://www.ncbi.nlm.nih.gov/pubmed/28830557
http://dx.doi.org/10.1186/s12985-017-0831-4
_version_ 1783258827667275776
author Sun, Xianliang
Zhang, Han
Xu, Shuiling
Shi, Lili
Dong, Jingjian
Gao, Dandan
Chen, Yan
Feng, Hao
author_facet Sun, Xianliang
Zhang, Han
Xu, Shuiling
Shi, Lili
Dong, Jingjian
Gao, Dandan
Chen, Yan
Feng, Hao
author_sort Sun, Xianliang
collection PubMed
description BACKGROUND: Induction of broad immune responses at mucosal site remains a primary goal for most vaccines against mucosal pathogens. Abundance of evidence indicates that the co-delivery of mucosal adjuvants, including cytokines, is necessary to induce effective mucosal immunity. In the present study, we set out to evaluate the role of a chemokine, CCL20, as an effective mucosal adjuvant for HIV vaccine. METHODS: To evaluate the role of CCL20 as a potent adjuvant for HIV vaccine, we examined its effects on antigen-specific antibody responses, level of antibody-secreting cells, cytokine production and intestinal homing of plasma cells in vaccine immunized mice. RESULTS: CCL20-incorporated VLP administered by mucosal route (intranasal (n = 10, p = 0.0085) or intravaginal (n = 10, p = 0.0091)) showed much higher potency in inducing Env-specific IgA antibody response than those administered by intramuscular route (n = 10). For intranasal administration, the HIV Env-specific IFN-γ(751 pg/ml), IL-4 (566 pg/ml), IL-5 (811 pg/ml) production and IgA-secreting plasma cells (62 IgA-secreting plasma cells/10(6) cells) in mucosal lamina propria were significantly augmented in CCL20-incorporated VLP immunized mice as compared to those immunized with Env only VLPs (p = 0.0332, 0.0398, 0.033, 0.0302 for IFN-γ, IL-4, IL-5, and IgA-secreting plasma cells, respectively). Further, anti-CCL20 mAb partially suppressed homing of Env-specific IgA ASCs into small intestine in mice immunized with CCL20-incorporated VLP by intranasal (62 decreased to 16 IgA- secreting plasma cells/10(6) cells, p = 0.0341) or intravaginal (52 decreased to 13 IgA- secreting plasma cells/10(6) cells, p = 0.0332) routes. CONCLUSION: Our data indicated that the VLP-incorporated CCL20 can enhance HIV Env-specific immune responses in mice, especially those occurring in the mucosal sites. We also found that i.m. prime followed by mucosal boost is critical and required for CCL20 to exert its full function as an effective mucosal adjuvant. Therefore, co-incorporation of CCL20 into Env VLPs when combined with mucosal administration could represent a novel and promising HIV vaccine candidate.
format Online
Article
Text
id pubmed-5568278
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-55682782017-08-29 Membrane-anchored CCL20 augments HIV Env-specific mucosal immune responses Sun, Xianliang Zhang, Han Xu, Shuiling Shi, Lili Dong, Jingjian Gao, Dandan Chen, Yan Feng, Hao Virol J Research BACKGROUND: Induction of broad immune responses at mucosal site remains a primary goal for most vaccines against mucosal pathogens. Abundance of evidence indicates that the co-delivery of mucosal adjuvants, including cytokines, is necessary to induce effective mucosal immunity. In the present study, we set out to evaluate the role of a chemokine, CCL20, as an effective mucosal adjuvant for HIV vaccine. METHODS: To evaluate the role of CCL20 as a potent adjuvant for HIV vaccine, we examined its effects on antigen-specific antibody responses, level of antibody-secreting cells, cytokine production and intestinal homing of plasma cells in vaccine immunized mice. RESULTS: CCL20-incorporated VLP administered by mucosal route (intranasal (n = 10, p = 0.0085) or intravaginal (n = 10, p = 0.0091)) showed much higher potency in inducing Env-specific IgA antibody response than those administered by intramuscular route (n = 10). For intranasal administration, the HIV Env-specific IFN-γ(751 pg/ml), IL-4 (566 pg/ml), IL-5 (811 pg/ml) production and IgA-secreting plasma cells (62 IgA-secreting plasma cells/10(6) cells) in mucosal lamina propria were significantly augmented in CCL20-incorporated VLP immunized mice as compared to those immunized with Env only VLPs (p = 0.0332, 0.0398, 0.033, 0.0302 for IFN-γ, IL-4, IL-5, and IgA-secreting plasma cells, respectively). Further, anti-CCL20 mAb partially suppressed homing of Env-specific IgA ASCs into small intestine in mice immunized with CCL20-incorporated VLP by intranasal (62 decreased to 16 IgA- secreting plasma cells/10(6) cells, p = 0.0341) or intravaginal (52 decreased to 13 IgA- secreting plasma cells/10(6) cells, p = 0.0332) routes. CONCLUSION: Our data indicated that the VLP-incorporated CCL20 can enhance HIV Env-specific immune responses in mice, especially those occurring in the mucosal sites. We also found that i.m. prime followed by mucosal boost is critical and required for CCL20 to exert its full function as an effective mucosal adjuvant. Therefore, co-incorporation of CCL20 into Env VLPs when combined with mucosal administration could represent a novel and promising HIV vaccine candidate. BioMed Central 2017-08-23 /pmc/articles/PMC5568278/ /pubmed/28830557 http://dx.doi.org/10.1186/s12985-017-0831-4 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Sun, Xianliang
Zhang, Han
Xu, Shuiling
Shi, Lili
Dong, Jingjian
Gao, Dandan
Chen, Yan
Feng, Hao
Membrane-anchored CCL20 augments HIV Env-specific mucosal immune responses
title Membrane-anchored CCL20 augments HIV Env-specific mucosal immune responses
title_full Membrane-anchored CCL20 augments HIV Env-specific mucosal immune responses
title_fullStr Membrane-anchored CCL20 augments HIV Env-specific mucosal immune responses
title_full_unstemmed Membrane-anchored CCL20 augments HIV Env-specific mucosal immune responses
title_short Membrane-anchored CCL20 augments HIV Env-specific mucosal immune responses
title_sort membrane-anchored ccl20 augments hiv env-specific mucosal immune responses
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5568278/
https://www.ncbi.nlm.nih.gov/pubmed/28830557
http://dx.doi.org/10.1186/s12985-017-0831-4
work_keys_str_mv AT sunxianliang membraneanchoredccl20augmentshivenvspecificmucosalimmuneresponses
AT zhanghan membraneanchoredccl20augmentshivenvspecificmucosalimmuneresponses
AT xushuiling membraneanchoredccl20augmentshivenvspecificmucosalimmuneresponses
AT shilili membraneanchoredccl20augmentshivenvspecificmucosalimmuneresponses
AT dongjingjian membraneanchoredccl20augmentshivenvspecificmucosalimmuneresponses
AT gaodandan membraneanchoredccl20augmentshivenvspecificmucosalimmuneresponses
AT chenyan membraneanchoredccl20augmentshivenvspecificmucosalimmuneresponses
AT fenghao membraneanchoredccl20augmentshivenvspecificmucosalimmuneresponses