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Principal Investigator: Sean Alex Gray
Organization: PAI LIFE SCIENCES, INC.
Fiscal Year: 2023
Award: $300,000
Funding agency: National Institute of Allergy and Infectious Diseases
ABSTRACT
Schistosomiasis is a major parasitic disease which could impact one billion people with 252 million currently
infected and 779 million at risk to acquire the infection in 74 countries. Current control strategies have relied on
repeated treatments with the drug praziquantel alone – however, this strategy has proven inadequate due to
minimal reduction of disease transmission, reinfection, and the inherent threat of drug resistance. Over the
course of 20 years, we have developed a potent schistosomiasis vaccine, termed SchistoShield®, targeting a
functionally important antigen, Sm-p80, formulated in the TLR4-targeted adjuvant, GLA-SE. SchistoShield® has
been exhaustively tested in numerous animal models and has consistently exhibited protection at all parasite life
stages. We are near completion of a Phase 1 safety and dose-ranging human clinical trial with SchistoShield® in
the US – with no serious safety signals reported – and will begin Phase 1B trials in Q3 of 2023 with a Phase 2
trial currently funded as well by the Bill and Melinda Gates Foundation. Despite the promise of SchistoShield®,
it is important to ready a next-generation follow-on candidate that builds a pipeline and serves as an alternative
should we encounter problems down the road in terms of e.g. scalability, cost, or field efficacy. To address these
concerns, we are proposing to evaluate two new variations on the current SchistoShield® vaccine: the first being
a redesigned Sm-p80 protein antigen, while the second being a novel RNA delivery platform version of the Sm-
p80 antigen.
For the redesign, we removed the hydrophobic and other irrelevant (outside of the catalytic triad domain) regions
of the ~85 kDa Sm-p80 antigen resulting in a smaller, and more antigenically focused, ~44 kDa antigen which
we have termed Catalysis-Targeted Constructs (CaTaCo™). CaTaCo™ is similar to Sm-p80 in that domains
required for enzymatic activity are maintained while soluble production yields are improved. Compared to Sm-
p80, CaTaCo™ exhibits minimal aggregation and less degradation -- a potential problem with the current antigen
that was flagged by the FDA for potential improvement. In mice, CaTaCo™ elicits comparatively high titers in
mice, binds to anti-Sm-p80 monoclonal antibodies (mAbs), and is detected by sera from mice and baboons
immunized with SchistoShield®.
With the increased use of RNA vaccines, we will also produce and evaluate both CaTaCo™ and Sm-p80 as
RNA vaccines using a proprietary technology invented by our partners at HDT Bio. HDT recently used this
technology for their COVID-19 vaccine HDT-301, which is similar to the COVID-19 vaccines from Moderna and
Pfizer/BioNTech. The HDT-301 platform consists of a self-replicating RNA (repRNA) adsorbed and stabilized on
a Lipid InOrganic Nanoparticle (LION™) carrier. This vaccine received emergency use approval in India – the
only self-amplifying platform to be approved in humans. Introduction of the repRNA into cells results in ongoing
biosynthesis of antigen-encoding RNA resulting in markedly higher protein concentrations in vivo leading to
enhanced humoral and cellular immune responses and - perhaps most importantly - a dose sparing effect. The
HDT-301 vaccine has been evaluated in both Phase 1 and Phase 2 human clinical trials trial in Brazil and the
US and has been shown to be safe while eliciting high anti-COVID-19 titers. In this SBIR, we propose to produce
both CaTaCo™ and Sm-p80 as repRNA/LION™ vaccines as well as the CaTaCo™ antigen, immunize them into
mice, and challenge with S. mansoni directly comparing each to the existing SchistoShield® vaccine. Successful
completion of this grant will address two key questions: 1) is an RNA vaccine for SchistoShield® feasible or
superior to the existing vaccine, and 2) whether the redesigned CaTaCo™ antigen is an improvement for the
next generation SchistoShield®.
Terms: <2019-nCoV vaccine><7S Gamma Globulin><Address><Adjuvant><Adsorption><Africa><Anabolism><Animal Model><Animal Models and Related Studies><Antibodies><Antigens><Antinuclear Antibodies><Antinuclear Factors><Asia><Baboons><Benchmarking><Best Practice Analysis><Bilharziasis><Binding><Biochemical><Body Tissues><Brazil><COVID-19><COVID-19 vaccine><COVID19><COVID19 vaccine><CV-19><CV19><Catalysis><Cell Body><Cell Communication and Signaling><Cell Signaling><Cells><Clinical Treatment Moab><Clinical Trials><Country><Disease><Disorder><Dose><Drug resistance><Drugs><Emergencies><Emergency Situation><Ensure><Evaluation><Exhibits><Fermentation><Foundations><Funding><Gene Transcription><Genetic Transcription><Grant><Homolog of Drosophila TOLL><Human><Hydrophobicity><IgG><Immune response><Immunize><Immunoglobulin G><Immunological response><India><Infection><Intracellular Communication and Signaling><Lead><Life><Lipids><Medication><Mice><Mice Mammals><Modern Man><Moderna COVID-19 vaccine><Moderna coronavirus disease 2019 vaccine><Molecular Interaction><Monoclonal Antibodies><Murine><Mus><Non-Polyadenylated RNA><Papio><Papios><Parasites><Parasitic Diseases><Pb element><Persons><Pharmaceutic Preparations><Pharmaceutical Preparations><Phase><Phase 1b Trial><Phase Ib Trial><Prasiquantel><Praziquantel><Production><Proteins><Protocol><Protocols documentation><RNA><RNA Expression><RNA Gene Products><RNA delivery><RNA replication><RNA vaccine><RNA-based vaccine><Recombinant Proteins><Reporting><Ribonucleic Acid><Risk><S mansoni><S. mansoni><SARS-CoV-2 vaccine><SARS-CoV2 vaccine><SARS-coronavirus-2 vaccine><SBIR><Safety><Savanna Baboons><Schistosoma mansoni><Schistosomatidae><Schistosomiasis><Severe Acute Respiratory Syndrome CoV 2 vaccine><Severe acute respiratory syndrome coronavirus 2 vaccine><Signal Transduction><Signal Transduction Systems><Signaling><Small Business Innovation Research><Small Business Innovation Research Grant><Solubility><South America><TLR4><TLR4 gene><Technology><Testing><Tissues><Toll Homologue><Transcription><Vaccines><Variant><Variation><anti-DNA autoantibody><anti-Sm><antiDNA autoantibody><benchmark><biological signal transduction><biosynthesis><blood fluke><clinical candidate><communicable disease transmission><comparative><corona virus disease 2019><corona virus disease 2019 vaccine><coronavirus disease 2019><coronavirus disease 2019 vaccine><coronavirus disease-19><coronavirus disease-19 vaccine><coronavirus infectious disease-19><cost><design><designing><disease transmission><drug candidate><drug resistant><drug/agent><egg><global health><heavy metal Pb><heavy metal lead><host response><human disease><immune system response><immunogen><immunoresponse><improved><in vivo><infectious disease transmission><invention><mAbs><mRNA vaccine><mRNA-1273><mRNA-based vaccine><mRNA1273><model of animal><monoclonal Abs><nCoV vaccine><nCoV-19 vaccine><nCoV19 vaccine><nano particle><nano-sized particle><nanoparticle><nanosized particle><new vaccines><next generation><next generation vaccines><novel><novel vaccines><phase 2 trial><phase II trial><protein p80><protein purification><resistance to Drug><resistant to Drug><toll-like receptor 4><tumor-related protein p80><vaccine against 2019-nCov><vaccine against SARS-CoV-2><vaccine against SARS-CoV2><vaccine against SARS-coronavirus-2><vaccine against Severe Acute Respiratory Syndrome CoV 2><vaccine against Severe acute respiratory syndrome coronavirus 2><vaccine candidate><vaccine for novel coronavirus>