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Imaging murine NALT following intranasal immunization with flagellin-modified circumsporozoite protein malaria vaccines.

Abstract：

:Intranasal (IN) immunization with a Plasmodium circumsporozoite (CS) protein conjugated to flagellin, a Toll-like receptor 5 agonist, was found to elicit antibody-mediated protective immunity in our previous murine studies. To better understand IN-elicited immune responses, we examined the nasopharynx-associated lymphoid tissue (NALT) in immunized mice and the interaction of flagellin-modified CS with murine dendritic cells (DCs) in vitro. NALT of immunized mice contained a predominance of germinal center (GC) B cells and increased numbers of CD11c+ DCs localized beneath the epithelium and within the GC T-cell area. We detected microfold cells distributed throughout the NALT epithelial cell layer and DC dendrites extending into the nasal cavity, which could potentially function in luminal CS antigen uptake. Flagellin-modified CS taken up by DCs in vitro was initially localized within intracellular vesicles followed by a cytosolic distribution. Vaccine modifications to enhance delivery to the NALT and specifically target NALT antigen-presenting cell populations will advance development of an efficacious needle-free vaccine for the 40% of the world's population at risk of malaria.

journal_name

Mucosal Immunol

journal_title

Mucosal immunology

authors

Nacer A,Carapau D,Mitchell R,Meltzer A,Shaw A,Frevert U,Nardin EH

doi

10.1038/mi.2013.48

subject

Has Abstract

pub_date

2014-03-01 00:00:00

pages

304-14

issue

2

eissn

1933-0219

issn

1935-3456

pii

mi201348

journal_volume

7

pub_type

杂志文章

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