Document text
Principal Investigator: Rong Xu
Organization: PROFECTUS BIOSCIENCES, INC.
Fiscal Year: 2020
Award: $69,471
Funding agency: National Institute of Allergy and Infectious Diseases
Abstract
Profectus Biosciences leverages its platform technologies of adjuvanted DNA vaccines to stimulate robust Th1-
biased immune responses likely necessary for protection against challenging viral diseases such as HIV. We
believe that optimized delivery methods are critical for development of effective genetic vaccines that can elicit
these types of responses. Like others, we often deliver our DNA-based vaccines using electroporation. However,
the logistical difficulties and pain associated with delivering vaccines via EP leads to doubt that it will ever be a
realistic delivery modality for mass vaccination with prophylactic vaccines. For this reason, there is strong interest
in development of alternative DNA delivery techniques. Ultrasound is a safe, non-invasive, effective method with
which microbubbles can be used to propel attached or associated payloads into permeabilized target tissues.
High acoustic ultrasound (well within FDA guidelines) of plasmid DNA with microbubbles induces unstable
oscillation and ultimate collapse of the latter, leading to minor cell membrane disruption that allows the plasmid
to enter nearby cells. Previous studies in animals have found ultrasound with microbubbles and plasmid DNA to
promote protein production in targeted organs. Under this application, we will develop ultrasound-mediated gene
transfer, or sonoporation, using microbubbles, as a painless replacement for electroporation. The ultrasound
delivery platform will be developed using our well-established plasmid DNA vaccine, which encodes the HIV
vaccine immunogen, Full-Length Single Chain (FLSC), and our IL-12 DNA adjuvant, as our “model” vaccine.
Although we will initially develop this sonoporation delivery technology for our HIV DNA vaccine, we believe that
this same delivery technology will be suitable for virtually any DNA- or mRNA-based vaccine. Therefore, the
development of this delivery technology should not only benefit the HIV vaccine field but the field of vaccinology
in general.
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Terms: <7S Gamma Globulin><AIDS Virus><Acoustic><Acoustics><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Adjuvant><Animal Model><Animal Models and Related Studies><Animals><Antibodies><Antibody Response><Antibody titer measurement><Antigens><Biologic Sciences><Biological Sciences><Bioscience><Body Tissues><Cell Body><Cell membrane><Cells><Collaborations><Control Groups><Cytoplasmic Membrane><DNA><DNA Vaccines><DNA delivery><Data><Deoxyribonucleic Acid><Development><Devices><Doctor of Philosophy><Domestic Rabbit><Echography><Echotomography><Edodekin Alfa><Electroporation><Gene Transfer><Generations><Grant><Guidelines><HIV><HIV Envelope Glycoprotein gp120><HIV Envelope Protein gp120><HIV env Protein gp120><HIV vaccine><HIV/AIDS Vaccines><HTLV-III gp120><Human><Human Immunodeficiency Viruses><IL-12><IL12><IgG><Immune response><Immunization><Immunoglobulin G><Immunologic Sensitization><Immunologic Stimulation><Immunological Sensitization><Immunological Stimulation><Immunological response><Immunostimulation><Injections><Interleukin-12><LAV-HTLV-III><Length><Life Sciences><Logistics><Lymphadenopathy-Associated Virus><Mass Vaccinations><Mechanics><Mediating><Medical Ultrasound><Messenger RNA><Methods><Mice><Mice Mammals><Microbubbles><Minor><Modality><Modeling><Modern Man><Murine><Mus><Muscle><Muscle Tissue><NKSF><Naked DNA Vaccines><Natural Killer Cell Stimulatory Factor><Organ><Oryctolagus cuniculus><Pain><Painful><Painless><Ph.D.><PhD><Plasma Membrane><Plasmids><Preventative vaccine><Preventive vaccine><Production><Prophylactic vaccine><Proteins><Proxy><Rabbits><Rabbits Mammals><Recombinant DNA Vaccines><Regimen><Reporter><Research><SBIR><SHIV><SIV><Scientist><Simian Immunodeficiency Viruses><Site><Small Business Innovation Research><Small Business Innovation Research Grant><Specific qualifier value><Specified><Splenocyte><Techniques><Technology><Testing><Tissues><Ultrasonic Imaging><Ultrasonogram><Ultrasonography><Ultrasound Diagnosis><Ultrasound Medical Imaging><Ultrasound Test><Uncertainty><Vaccinated><Vaccine Antigen><Vaccines><Viral Diseases><Virus Diseases><Virus-HIV><Work><adaptive immune response><adaptive immunity><antibody titering><base><deliver DNA><developmental><diagnostic ultrasound><doubt><effectiveness measure><electroporative delivery><experience><gene electrotransfer><genetic vaccine><gp120><gp120 ENV Glycoprotein><gp120(HIV)><host response><human immunodeficiency virus vaccine><immunogen><immunoresponse><in vivo><indexing><interest><mRNA><mechanical><model of animal><model organism><muscular><non-human primate><non-painful><nonhuman primate><nonpainful><not painful><novel><plasmalemma><plasmid DNA><response><simian HIV><simian human immunodeficiency virus><sonogram><sonography><sonoporation><sound measurement><success><ultrasound><ultrasound imaging><ultrasound scanning><user-friendly><vaccination study><vaccination trial><vaccine delivery><vaccine study><vaccine trial><vaccinology><viral infection><virtual><virus infection><virus-induced disease>