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BALTIMORE, MD, United States

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 238.76K | Year: 2014

DESCRIPTION: There is a growing consensus that protection against HIV infection will require BOTH antiviral antibody responses as well as polyfunctional CD4+ and CD8+ T cells with potent lytic activity. To stimulate the breadth, potency, and rate of response required, Profectus Biosciences intends to utilize its platform technologies based on electroporation of DNA vaccines combined with genetic adjuvants. As a step in that direction, a recent phase 1 clinical trial, HVTN-080, showed that electroporation incombination with our IL-12 adjuvant can double the CD4+ and CD8+ T cell response rate in vaccinees over electroporation alone1. Even with this success, we recognize that a truly effective HIV vaccine will require a regimen that can consistently provide high magnitude, long-lived responses at rates gt95% with as few booster immunizations as possible. We believe that adjuvants are a key to developing such a vaccine. Under a previous phase I SBIR, we identified a new class of genetic adjuvants that exploi

Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 998.49K | Year: 2015

DESCRIPTION The HIV pandemic is one of the greatest public health challenges in history It is estimated that million people are living with HIV and million of those are newly infected In a number of developed countries the risk of death associated with HIV infection has sharply declined due to the use of highly active antiretroviral therapy HAART Unfortunately the rate of new HIV infections remains undiminished even with the ever increasing availability of prevention programs and HAART For these reasons a vaccine that could prevent or control the spread of HIV is urgently needed A recent study showed that a skin delivered therapeutic DNA vaccine co formulated with a novel adjuvant stimulated mucosal T cell responses in SIV infected macaques and led to durable viral suppression in a subset of animals after stopping ART These results are in striking contrast to previous therapeutic vaccines employing intramuscular delivery of DNA that failed to induce an effect or at best induced a log reduction in viremia or transient control of viral rebound We propose to make therapeutic DNA vaccination even more effective by using a more potent combination of drugs cART to maximize the effects of the vaccine using a more potent adjuvant strategy that increases DNA vaccine induction of antibody and T cell responses and stimulates homing of these responses to gut associated lymphoid tissues and using a novel electroporation DNA delivery device that more efficiently delivers DNA into the skin a more immunocompetent site than muscle for induction of systemic and mucosal responses Our overarching hypothesis is that a vaccine induced functional cure will be mediated by strong mucosal responses and that increasing and focusing these responses to the gut in maximally suppressed infections via use of an optimized mucosal adjuvant and delivery into skin will maximally reduce or prevent residual viruses from emerging from the gut reservoir after stopping cART To this end we have assembled a panel of four DNA based adjuvants that we hypothesize will induce robust anti HIV mucosal and systemic immune responses when combined Under this fast track SBIR we will investigate adjuvant combinations with our HIV SIV multi antigen MAG DNA vaccine consisting of plasmids expressing env gp a gag pol fusion and a nef tat vif fusion We anticipate that an optimal combination of these adjuvants will elevate the performance of our MAG DNA vaccine to a level worthy of human trials PUBLIC HEALTH RELEVANCE The objective of this project is to define an optimal combination of adjuvants and delivery regimen for our therapeutic HIV SIV DNA vaccine Such optimization of any HIV SIV therapeutic vaccine will be necessary for that vaccine to successfully combat established HIV SIV infections

Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 299.92K | Year: 2016

ABSTRACT A universal influenza vaccine is believed to be possible if conserved regions of influenza are effectively targeted and appropriate immune responses are generated against those targets The enhanced safety stability and accelerated product development generally provided by DNA vaccination make it an appealing approach to develop such a universal influenza vaccine Unfortunately immune responses to universal influenza antigens are typically weak and in the past DNA vaccination of humans has been disappointing To overcome these and other obstacles to developing an effective practical and truly universal influenza vaccine we intend to deliver our vaccine using a DNA prime protein boost regimen and employ novel immunogens derived from the following three conserved influenza A antigens the stem region of hemagglutinin HA the matrix protein ectodomain M e and the nucleoprotein NP We believe that together these antigens will evoke the immunological breadth necessary to protect against a broad range of both seasonal and potential pandemic influenza strains We will also use a potent DNA adjuvant combination to maximize immunogenicity and to tune the responses toward a Th phenotype Finally we will utilize a recombinant protein boost to amplify the humoral immune responses and increase their durability In this Phase I SBIR we will construct and express our influenza A immunogens and verify their immunogenicity and protective efficacy in mice to determine if the vaccine provides a wide breadth of protection from divergent seasonal and pandemic influenza A strains If we are successful in this Phase I proof of concept study we will move on to test our vaccine in a macaque challenge model under a Phase II application and begin development on influenza B and possibly type C immunogens PROJECT NARRATIVE The objective of this project is to develop a DNA prime subunit boost universal influenza vaccine Such a vaccine is needed to combat seasonal and pandemic influenza outbreaks and to lessen the dependency on seasonal vaccines

Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 733.63K | Year: 2016

DESCRIPTION provided by applicant Our primary approach to develop an effective prophylactic vaccine against HIV utilizes a novel immunogen called the Full Length Single Chain FLSC that consists of gp derived from HIV genetically linked via a amino acid linker to the D D domains of human CD When rhesus macaques were inoculated with versions of FLSC that contain CD derived from rhesus macaques and either HIV gp or SIV gp significant protection against rectal challenge with multiple low doses of either an R tropic heterologous SHIV P or heterologous SIVmac was observed These observations propelled FLSC into preclinical development and evaluation in a phase clinical trial supported by BMGF MHRP NIAID Further vaccination with DNA expressing FLSC and IL administered by electroporation in macaques induces multifunctional T cells that are known to correlate with protection and improved efficacy In our most recent macaque study a FLSC DNA prime protein boost regimen yielded efficacy against a cross clade challenge In collaboration with others we have also developed a DNA protein co delivery regimen that evokes higher titered longer lived anti FLSC responses However we believe that our approach can be dramatically improved by targeting these anti FLSC responses to mucosal sites where HIV enters the host and establishes infections To improve mucosal immune responses we sought to develop a mucosal homing DNA adjuvant that targets lymphocytes to mucosal immune effector sites after systemic vaccination In preliminary studies we identified two putative mucosal homing DNA adjuvants Under phase I we demonstrated that one of these putative adjuvants does indeed induce the homing of lymphocytes to mucosal immune effector sites after systemic i m immunization Under phase II we intend to expand upon these observations and demonstrate that this adjuvant targets vaccine specific immune responses to mucosal sites in primates PUBLIC HEALTH RELEVANCE The objective of this project is to determine if a mucosal homing DNA adjuvant will improve the immune responses generated by our HIV SIV vaccine regimen

Profectus Biosciences, Inc. | Date: 2010-03-25

The invention relates to compounds of formulae (1) and (2): and pharmaceutically acceptable salts thereof for the treatment of cancer, inflammation, auto-immune diseases, diabetes and diabetic complications, infection, cardiovascular disease and ischemia-reperfusion injuries.

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