ST-2560, a selective inhibitor of the Na1.7 sodium channel, affects nocifensive and cardiovascular reflexes in non-human primates.

Background And Purpose: The voltage-gated sodium channel isoform Na1.7 is a high-interest target for the development of non-opioid analgesics due to its preferential expression in pain-sensing neurons. Na1.

IL-12-assisted immunization against Listeria monocytogenes using replication-restricted VSV-based vectors.

Co-administration of IL-12 with vaccine immunogens has proven to be an effective strategy for eliciting potent Th1-biased immunity. Unfortunately, the use of IL-12 as a vaccine component has been limited because it is unstable at ambient temperatures, expensive to produce, and toxic when administered at excessive dosages. Using reverse genetics, we created a recombinant replication-restricted vesicular stomatitis virus that expresses large quantities of an IL-12 fusion protein (VSVDeltaG-IL12F), but can only establish a single round of infection because the genome does not encode the viral glycoprotein (G protein) that is required for viral entry into host cells.

Recombinant replication-restricted VSV as an expression vector for murine cytokines.

Vesicular stomatitis virus (VSV) is a prototypic non-segmented, negative-strand RNA virus that rapidly and efficiently shuts down the production of host cell-encoded proteins and utilizes the cell's protein production machinery to express high levels of virally encoded proteins. In an effort to take advantage of this characteristic of VSV, we have employed a reverse genetics system to create recombinant forms of VSV encoding a variety of murine cytokines. Previous studies have revealed that cells infected with recombinant VSV that lack expression of the surface glycoprotein (G protein), designated deltaG-VSV, more efficiently express and secrete recombinant proteins than do recombinant "wild-type" VSV.

Adjuvanticity of an IL-12 fusion protein expressed by recombinant deltaG-vesicular stomatitis virus.

The remarkable immunomodulatory and adjuvant properties of rIL-12 have been well described. Many early studies documenting the adjuvanticity of IL-12 were performed using the murine model of Listeria monocytogenes infection. In this report, we describe the construction of an attenuated recombinant vesicular stomatitis virus (VSV-deltaG) that encodes a single-chain IL-12 fusion protein (IL-12F), and the use of this virus as an expression vector to produce large quantities of IL-12F.