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

Nobuyuki Matoba, Aude Magérus, Brian C. Geyer, Yunfang Zhang, Mrinalini Muralidharan, Annette Alfsen, Charles J. Arntzen, Morgane Bomsel, Tsafrir Leket-Mor

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

Abstract

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 galactosyl-ceramide-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-ceramide and GM1 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 mucosally 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.

Original languageEnglish (US)
Pages (from-to)13584-13589
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number37
DOIs
StatePublished - Sep 14 2004

ASJC Scopus subject areas

  • General

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