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Systemic immunization with CCL27/CTACK modulates immune responses at mucosal sites in mice and macaques
Journal article   Open access   Peer reviewed

Systemic immunization with CCL27/CTACK modulates immune responses at mucosal sites in mice and macaques

Kimberly A Kraynyak, Michele A Kutzler, Neil J Cisper, Amir S Khan, Ruxandra Draghia-Akli, Niranjan Y Sardesal, Mark G Lewis, Jian Yan and David B Weiner
Vaccine, v 28(8), pp 1942-1951
2010
PMID: 20188250
url
https://doi.org/10.1016/j.vaccine.2009.10.095View
Published, Version of Record (VoR) Open

Abstract

DNA vaccine HIV-1 Adjuvant Mucosal CCL27
Plasmid DNA is a promising vaccine platform that has been shown to be safe and able to be administered repeatedly without vector interference. Enhancing the potency of DNA vaccination through co-delivery of molecular adjuvants is one strategy currently under investigation. Here we describe the use of the novel chemokine adjuvant CCL27/CTACK to enhance immune responses to an HIV-1 or SIV antigen in mice and rhesus macaques. CCL27 has been shown to play a role in inflammatory responses through chemotaxis of CCR10+ cells, and we hypothesized that CCL27 may modulate adaptive immune responses. Immunizations in mice with HIV-1gag/CCL27 enhanced immune responses both at peripheral and, surprisingly, at mucosal sites. To confirm these findings in a large-animal model, we created optimized CCL27 and SIV antigenic plasmid constructs for rhesus macaques. 10 macaques ( n = 5/group) were immunized intramuscularly with 1 mg/construct of antigenic plasmids ± CCL27 with electroporation. We observed significant IFN-γ secretion and CD8+ T-cell proliferation in peripheral blood. Interestingly, CCL27 co-immunized macaques exhibited a trend toward greater effector CD4+ T cells in the bronchiolar lavage (BAL). CCL27 co-delivery also elicited greater antigen-specific IgA at unique sites including BAL and fecal samples but not in the periphery. Future studies incorporating CCL27 as an adjuvant in vaccine or therapy models where eliciting immune responses in the lung are warranted.

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Collaboration types
Industry collaboration
Domestic collaboration
Web of Science research areas
Immunology
Medicine, Research & Experimental
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