A mucosally targeted subunit vaccine candidate eliciting HIV-1 transcytosis-blocking Abs

被引:71
作者
Matoba, N
Magérus, A
Geyer, BC
Zhang, YF
Muralidharan, M
Alfsen, A
Arntzen, CJ
Bomsel, M
Mor, TS
机构
[1] Arizona State Univ, Sch Life Sci, Tempe, AZ 85287 USA
[2] Arizona State Univ, Biodesign Inst, Tempe, AZ 85287 USA
[3] Inst Cochin Genet Mol, Dept Biol Cellulaire, F-75014 Paris, France
关键词
D O I
10.1073/pnas.0405297101
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
A vaccine that would engage the mucosal immune system against a broad range of HIV-1 subtypes and prevent epithelial transmission is highly desirable. Here we report fusing the mucosal targeting B subunit of cholera toxin to the conserved galactosylceramide-binding domain (including the ELDKWA-neutralizing epitope) of the HIV-1 gp41 envelope protein, which mediates the transcytosis of HIV-1 across the mucosal epithelia. Chimeric protein expressed in bacteria or plants assembled into oligomers that were capable of binding galactosyl-ceramicle and Gm, gangliosides. Mucosal (intranasal) administration in mice of the purified chimeric protein followed by an i.p. boost resulted in transcytosis-neutralizing serum IgG and mucosal IgA responses and induced immunological memory. Plant production of muco-sally targeted immunogens could be particularly useful for immunization programs in developing countries, where desirable product traits include low cost of manufacture, heat stability, and needle-free delivery.
引用
收藏
页码:13584 / 13589
页数:6
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