Transport of an influenza virus vaccine formulation (iscom) in
human intestinal epithelial (caco-2) cells.
Lazorova, Lucia, Per Artursson, Ake Engstrom, and Anders
Sj[diaeresis]olander.
Uppsala University, Department of Pharmacy-Pharmaceutics,
Biomedicum, Box 580, S-751 23 Uppsala, Sweden, Uppsala University,
Department of Medical and Physiological Chemistry, Biomedicum, Box
575, S-751 23 Uppsala, Sweden, National Veterinary Institute,
Department of Veterinary Virology, Biomedicum, Box 585, S-751 23
Uppsala
APStracts 2:0226G, 1995.
The influenza virus envelope glycoproteins haemagglutinin and
neuraminidase were administered to the apical or basolateral sides of
Caco-2 monolayers either as native protein micelles (mic-ag) or after
incorporation into the orally active adjuvant formulation, iscoms
(isc-ag). Biotin-conjugated isc-ag were localized in intracellular
vesicles as early as 2 min after administration to the apical side at
37 C. Ten minutes after administration, both intracellular vesicles
and intercellular spaces were labelled, and extracellular labelling
was observed on the basolateral side of the cells, indicating that
isc-ag were transported across the epithelium within 10 min of
exposure. The transport of 125I-labelled isc-ag and mic-ag in the
apical to basolateral and basolateral to apical directions across
Caco-2 monolayers was comparable at 37 C. Gel chromatography analysis
revealed that only 0.55-3.1 % of the transported isc-ag and mic-ag
had a molecular weight > 5,000 while 21.0-42.3 % was eluted at a
position corresponding to peptides of approximately 10 amino acids.
Although isc-ag and mic-ag were transported and degraded by Caco-2
monolayers in comparable amounts, only the transported isc-ag induced
a dose dependent proliferative response in vitro of T cells primed
with influenza virus antigen. High performance gel chromatography and
reverse phase HPLC indicated that the transported antigenic isc-ag
consisted of hydrophobic peptides with a molecular weight
Received 16 May 1994; accepted in final form 26 September 1995.
APS Manuscript Number G179-4.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 November 95