A mucosally targeted subunit vaccine candidate eliciting HIV-1 transcytosis-blocking Abs.
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-ceramide and G(M1) 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.
Matoba
Nobuyuki
N
School of Life Sciences and Biodesign Institute, P.O. Box 874501, Arizona State University, Tempe, AZ 85287-4501, USA.
Magérus
Aude
A
Geyer
Brian C
BC
Zhang
Yunfang
Y
Muralidharan
Mrinalini
M
Alfsen
Annette
A
Arntzen
Charles J
CJ
Bomsel
Morgane
M
Mor
Tsafrir S
TS
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000281:Administration, Intranasal; D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D005822:Genetic Vectors / Q000235:genetics; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology*; D015497:HIV-1 / Q000276:immunology*; D018928:Immunity, Mucosal / Q000276:immunology*; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D014026:Nicotiana / Q000235:genetics; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology
D016915:AIDS Vaccines; D015483:HIV Antibodies; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D014614:Vaccines, Synthetic