Abstract: Multiple sequential screening tests have been performed on phage display libraries, and polypeptide sequences have been identified that potently drive both: (i) intake into mucosal immune cells, including NALT cells in the nose and throat; and, (ii) phagocytic intake and processing by antigen-presenting cells, such as macrophages. Such polypeptide sequences can be used as potent “target and deliver” components in vaccines that can be administered nasally, or to other mucous membranes. Such vaccines can be made very rapidly and in huge quantities, from bacteriophages that will also carry antigenic sequences in their coat proteins, or other immunoactive components. Alternately, such “target and deliver” polypeptides can be incorporated into vaccines derived from eukaryotic viruses or cellular pathogens. Enhancements also are disclosed, such as agents that can activate one or more types of toll-like receptors, to increase immunes responses and guide them in desired directions.

Abstract: A treatment method and genetic vectors are disclosed for non-invasive delivery of polypeptides through the blood brain barrier (BBB), to treat brain or spinal tissue. A genetic vector is used to transfect one or more neurons which “straddle” the BBB, such as sensory neurons, nocioceptive neurons, or lower motor neurons; this is done by administering the vector in a manner that causes it to contact neuronal projections that extend outside the BBB. Once inside a peripheral projection that belongs to a BBB-straddling neuron, the vectors (or some portion thereof) will be transported to the main cell body of the neuron, through a process called retrograde transport. Inside the main cell body, at least one gene carried by the genetic vector will be expressed, to form polypeptides. Some of these polypeptides (which can include leader sequences that will promote anterograde transport and secretion by BBB-straddling neurons) will be transported by the neurons to secretion sites inside the BBB.