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A strategy of antigen incorporation into exosomes: comparing cross-presentation levels of antigens delivered by engineered exosomes and by lentiviral virus-like particles.

Abstract：

:Among strategies aimed at developing new nanoparticle-based vaccines, exosomes hold much promise. They are nanovesicles released by basically all eukaryotic cell types originating from intraluminal vesicles which accumulate in multivesicular bodies. Exosomes have immunogenic properties whose strength correlates with the amounts of associated antigens. Engineering antigens to target them in exosomes represents the last frontier in terms of nanoparticle-based vaccines. Here we report a new method to incorporate protein antigens in exosomes relying on the unique properties of a mutant of the HIV-1 Nef protein, Nef(mut). This is a biologically inactive mutant we found incorporating into exosomes at high levels also when fused at its C-terminus with foreign proteins. We compared both biochemical and antigenic properties of Nef(mut) exosomes with those of previously characterized Nef(mut) -based lentiviral virus-like particles (VLPs). We found that exosomes incorporate Nef(mut) and fusion protein derivatives with similar efficiency of VLPs. When an envelope fusion protein was associated with both exosomes and VLPs to favor cross-presentation of associated antigens, Nef(mut) and its derivatives incorporated in exosomes were cross-presented at levels at least similar to what observed when the antigens were delivered by engineered VLPs. This occurred despite exosomes entered target cells with an apparent lower efficiency than VLPs. The unique properties of HIV-1 Nef(mut) in terms of exosome incorporation efficiency, carrier of foreign antigens, and lack of anti-cellular effects open the way toward the development of a flexible, safe, cost-effective exosome-based CD8(+) T cell vaccine platform.

journal_name

Vaccine

journal_title

Vaccine

authors

Lattanzi L,Federico M

doi

10.1016/j.vaccine.2012.10.010

subject

Has Abstract

pub_date

2012-11-26 00:00:00

pages

7229-37

issue

50

eissn

0264-410X

issn

1873-2518

pii

S0264-410X(12)01456-9

journal_volume

30

pub_type

杂志文章

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