Profectus BioSciences has in-licensed several powerful vaccine delivery platforms that can be used either alone or in combination to improve therapeutic outcomes. Profectus has also assembled the manufacturing capacity to make each approach a real plug & play opportunity, vastly simplifying the construction and production of clinical trial materials. Our therapeutic vaccine program is focused on indications in the antiviral market where there are still high unmet needs, namely HCV, HPV, HSV, and HIV.

pDNA Vaccines. DNA vaccines prompt the host cells at the site of immunization to express selected protein subunits of the target pathogen. Since their discovery, DNA vaccines are viewed as an extremely promising vaccine modality. It has had success in the animal vaccine market but has been plagued by poor immunogenicity in clinical trials for human vaccines. The Vaccine Technology portfolio licensed by Profectus solves this problem in three ways.

First, Profectus coformulates plasmids with Bupivacaine, a small molecule analgesic that stabilizes pDNA vaccines by innervating with pDNA helix and improving delivery into the target tissue.

Second, the immunogen expressing plasmid is coformulated with plasmids expressing the potent Molecular Adjuvant IL-12. This adjuvant provides the necessary "kick-start" for the desired immune response once the plasmids enter the cell. The Company has also in-licensed an additional adjuvant technology from UMB that uses the enzymatically-active region of cholera toxin (CTA1) in order to facilitate the induction of potent and potentially protective immune reponses to the target pathogen.

Third, pDNA formulations are delivered via Electroporation. Profectus has an agreement with Ichor Medical Systems (www.ichorms.com) that allows access to their TriGridTM technology and their innovative devices for delivery of Profectus’s pDNA vaccines. The result is a significant improvement to pDNA vaccine delivery and the resulting immune response.

The combination of these improvements is necessary to truly realize the promise that pDNA vaccines have to alter the clinical outcome of patients infected with HCV, HIV, HPV, or HSV.

Vesicular stomatitis virus (rVSV) Vectored Vaccines. VSV is a negative-strand, non-segmented RNA virus from the order Mononegavirales that has been redesigned to enable delivery of vaccine immunogens. The rVSV technology in-licensed by Profectus was originally developed in the laboratories of Jack Rose, Ph.D. of Yale University and further optimized and attenuated by investigators at Wyeth. VSV is a particularly attractive candidate for this purpose because its genome can accommodate more than one foreign gene and contains its own adjuvant that activates the immune system through TLR7. Since their replication is cytoplasmic, and their genomes are comprised of RNA, rVSV are incapable of integrating within the genomes of infected host cells – a highly desirable safety feature. Unlike Adenovirus and other viral vector vaccines employed today, human infection with VSV is rare, so the general population is free of pre-existing, virus-neutralizing immunity that would prevent the vaccine from “taking” in the immunized person and attenuating any resulting efficacy. Recombinant VSV vectors replicate with a high degree of efficiency and elicit potent humoral and cellular responses against the target pathogen. Numerous papers from Jack Rose, Ph.D. and the team at Profectus demonstrate the potential of rVSV as a vaccine vector. Profectus is exploiting this technology to develop effective therapeutic vaccines.

Transition-State Vaccines The Company is developing a novel HIV Vaccine Immunogen based on its proprietary strategy called Transition-State Vaccines. This strategy was in licensed from UMB and is designed to target immune responses to conserved portions of viral spikes through the use of chimeric fusions. These fusions are composed of portions of the viral surface spike and a small binding portion of its cognate receptor via a small amino acid linker. The linker is sufficiently long that the two components will interact to complete an intermolecular bond. Such immunogens redirect the immune response away from highly variable regions of the envelope spike that usually act as immunological decoys to regions that are highly conserved. For HIV, these conserved regions could be the “Achilles heel” for all HIV isolates. These constructs are produced from a single construct, thus allowing production in a variety of mammalian cell systems. It can also be incorporated into both DNA and vectored vaccines in order to stimulate key cellular responses such as CTLs.