Transport of an influenza virus vaccine formulation (iscom) in Caco-2 cells.

The influenza virus envelope glycoproteins hemagglutinin 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, immune stimulating complexes (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 degrees C. Ten minutes after administration, both intracellular vesicles and intercellular spaces were labeled, and extracellular labeling was observed on the basolateral side of the cells, indicating that isc-ag were transported across the epithelium within 10 min of exposure. Transport of 125I-labeled isc-ag and mic-ag in the apical-to-basolateral and basolateral-to-apical directions across Caco-2 monolayers was comparable at 37 degrees C. Gel chromatography analysis revealed that only 0.55-3.1% of transported isc-ag and mic-ag had a molecular weight of > 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 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 high-performance liquid chromatography indicated that transported antigenic isc-ag consisted of hydrophobic peptides with a molecular weight of < or = 3,000. These results indicate that antigens incorporated into the orally active adjuvant formulation iscom are degraded to antigenic peptides during transport across the intestinal epithelium.

Human effects of veterinary biological products.

A 14-year-old male drank two glasses of milk from a gallon inoculated with 21 vials of live virus vaccine intended to immunize 1000 baby chicks against Newcastle Disease. The patient was managed with catharsis and careful observation, and remained completely asymptomatic in the following 28 days. Newcastle Disease virus (NDV) may cause paralytic neurotropic, viscerotropic, or pneumonotropic disease in chickens, but has limited effects on humans. Systemic exposure to this vaccine has not previously been reported in humans, although an aerosol NDV vaccine has caused self-limited conjunctivitis following ocular exposure. The human effects of veterinary biologicals remain poorly defined. The limited literature existing in regards to the human experience with common veterinary vaccines is reviewed.