SBIR-STTR Award

A Novel TLR5 Agonist-Based Adjuvant for Poliovirus Vaccine
Award last edited on: 1/24/2018

Sponsored Program
SBIR
Awarding Agency
NIH : NIAID
Total Award Amount
$581,198
Award Phase
2
Solicitation Topic Code
NIAID
Principal Investigator
Vadim Mett

Company Information

Buffalo Biolabs LLC

73 High Street
Buffalo, NY 14203
   (716) 849-6810
   info@buffalobiolabs.com
   www.buffalobiolabs.com
Location: Single
Congr. District: 26
County: Erie

Phase I

Contract Number: ----------
Start Date: ----    Completed: ----
Phase I year
2016
Phase I Amount
$288,029
Antiviral vaccines remain the largest segment of the rapidly growing global vaccine market. Despite near-complete eradication of poliovirus through vaccination efforts, continued need for inactivated polio vaccine (IPV) is projected to reach 450 million doses per year worldwide. Among major obstacles to widespread use of the current IPV formulation are its high cost and insufficient potency to induce robust intestinal immunity. Therefore, development of an effective, safe and affordable adjuvant for IPV that would allow reduction of the costly IPV antigen content represents a highly significant unmet need. This Phase I SBIR proposal aims to address this challenge through optimization of a novel adjuvant system combining the immunostimulatory power of the toll-like receptor 5 (TLR5) agonist, entolimod (previously CBLB502), with the well- known adjuvant properties of Alum. Entolimod is being developed for tissue protective (anti- radiation and supportive care in cancer treatment) and anticancer immunotherapeutic applications by Cleveland BioLabs, Inc. (CBLI) and has an established safety profile. Given the demonstrated adjuvant properties of the natural TLR5 agonist (and entolimod parent) flagellin, investigators of this proposal in partnership with CBLI developed an innovative [entolimod+Alum]-based adjuvant system (termed SA702) with advantages in terms of efficacy (combined effect of two adjuvants), versatility (modular platform easily customized for many different antigen types); and decreased futile (adjuvant-directed) immunogenicity. Preliminary studies confirmed that immunization of mice with IPV (10% human dose) co-adsorbed on SA702 led to induction of increased levels of anti-poliovirus neutralizing antibodies compared to immunization with IPV alone or [IPV+Alum]. Here, we propose further optimization of entolimod as a co-adjuvant through targeting of its residual immunogenicity and its ancillary inflammasome-directed signaling activity (Aim 1) followed by characterization and optimization of the stability, efficacy and safety of SA702-IPV formulations containing the identified optimal entolimod variant (Aim 2). In addition, we will determine the impact of entolimod's residual immunogenicity on adjuvant activity of SA702 via mapping and elimination of mouse T cell epitopes. Together, the deliverables of these aims will define and validate an optimal design for the SA702 platform and a new SA702-IPV formulation and set the stage for Phase II SBIR application and commercialization.

Public Health Relevance Statement:
Project Narrative The proposed development of a novel modular and versatile adjuvant system combining a rationally optimized agonist of the TLR5 innate immunity receptor with Alum will address a significant medical need for potent, safe and affordable poliovirus vaccine formulation and open additional opportunities on the rapidly growing global vaccine market.

NIH Spending Category:
Biodefense; Biotechnology; Emerging Infectious Diseases; Immunization; Infectious Diseases; Neurodegenerative; Prevention; Rare Diseases; Vaccine Related

Project Terms:
Address; Adjuvant; Adsorption; Agonist; Alhydrogel; aluminum sulfate; Antigens; Antiviral Agents; Applications Grants; base; Businesses; cancer therapy; cell motility; Clinical; Clinical Trials; Collaborations; commercialization; cost; cost effective; design; Development; Disease; Dose; Elements; Employee Strikes; Engineering; FDA approved; Flagellin; Formulation; Foundations; Goals; Human; Human Papilloma Virus Vaccine; Human poliovirus; Immune response; Immunity; Immunization; immunogenicity; Immunologic Adjuvants; Immunotherapeutic agent; improved; Incidence; influenzavirus; innovation; Intestines; Letters; low and middle-income countries; Maps; Marketing; Medical; Modification; Mouse Strains; Mus; Natural Immunity; Nature; neutralizing antibody; NF-kappa B; novel; Parents; Phase; Poliomyelitis; Poliovirus Vaccines; Property; Proteins; Radiation; rapid growth; receptor; Recombinant Vaccines; Research Personnel; Residual state; Safety; Salmonella; Signal Transduction; Small Business Innovation Research Grant; Splenocyte; Staging; success; Supportive care; System; T-Lymphocyte Epitopes; Technology; Testing; Tissues; TLR4 gene; TLR5 gene; TLR9 gene; Toll-like receptors; Toxicology; Vaccinated; Vaccination; Vaccine Antigen; vaccine development; Vaccines; Variant; Viral Antigens; Virus; Virus Activation; Virus Diseases; World Health Organization

Phase II

Contract Number: ----------
Start Date: ----    Completed: ----
Phase II year
2017
Phase II Amount
$293,169
Antiviral vaccines remain the largest segment of the rapidly growing global vaccine market. Despite near-complete eradication of poliovirus through vaccination efforts, continued need for inactivated polio vaccine (IPV) is projected to reach 450 million doses per year worldwide. Among major obstacles to widespread use of the current IPV formulation are its high cost and insufficient potency to induce robust intestinal immunity. Therefore, development of an effective, safe and affordable adjuvant for IPV that would allow reduction of the costly IPV antigen content represents a highly significant unmet need. This Phase I SBIR proposal aims to address this challenge through optimization of a novel adjuvant system combining the immunostimulatory power of the toll-like receptor 5 (TLR5) agonist, entolimod (previously CBLB502), with the well- known adjuvant properties of Alum. Entolimod is being developed for tissue protective (anti- radiation and supportive care in cancer treatment) and anticancer immunotherapeutic applications by Cleveland BioLabs, Inc. (CBLI) and has an established safety profile. Given the demonstrated adjuvant properties of the natural TLR5 agonist (and entolimod parent) flagellin, investigators of this proposal in partnership with CBLI developed an innovative [entolimod+Alum]-based adjuvant system (termed SA702) with advantages in terms of efficacy (combined effect of two adjuvants), versatility (modular platform easily customized for many different antigen types); and decreased futile (adjuvant-directed) immunogenicity. Preliminary studies confirmed that immunization of mice with IPV (10% human dose) co-adsorbed on SA702 led to induction of increased levels of anti-poliovirus neutralizing antibodies compared to immunization with IPV alone or [IPV+Alum]. Here, we propose further optimization of entolimod as a co-adjuvant through targeting of its residual immunogenicity and its ancillary inflammasome-directed signaling activity (Aim 1) followed by characterization and optimization of the stability, efficacy and safety of SA702-IPV formulations containing the identified optimal entolimod variant (Aim 2). In addition, we will determine the impact of entolimod's residual immunogenicity on adjuvant activity of SA702 via mapping and elimination of mouse T cell epitopes. Together, the deliverables of these aims will define and validate an optimal design for the SA702 platform and a new SA702-IPV formulation and set the stage for Phase II SBIR application and commercialization.

Public Health Relevance Statement:
Project Narrative The proposed development of a novel modular and versatile adjuvant system combining a rationally optimized agonist of the TLR5 innate immunity receptor with Alum will address a significant medical need for potent, safe and affordable poliovirus vaccine formulation and open additional opportunities on the rapidly growing global vaccine market.

Project Terms:
Address; Adjuvant; Adsorption; Agonist; aluminum sulfate; Antigens; Antiviral Agents; Applications Grants; base; Businesses; cancer therapy; cell motility; Clinical; clinical development; Clinical Trials; Collaborations; commercialization; cost; cost effective; Custom; design; Development; Disease; Dose; Elements; Employee Strikes; Engineering; FDA approved; Flagellin; Formulation; Foundations; Goals; Human; Human Papilloma Virus Vaccine; Human poliovirus; Immunity; Immunization; Immunize; immunogenicity; Immunologic Adjuvants; Immunotherapeutic agent; improved; Inbred BALB C Mice; Incidence; Industrialization; Inflammasome; influenzavirus; Innate Immune Response; innovation; Intestines; Letters; low and middle-income countries; Medical; Modification; Mouse Strains; Mus; Natural Immunity; Nature; neutralizing antibody; NF-kappa B; novel; Pharmacology; Phase; Poliomyelitis; Poliovirus Vaccines; Property; Proteins; Radiation; rapid growth; receptor; Recombinant Vaccines; Research Personnel; Residual state; Safety; Salmonella; Signal Transduction; Small Business Innovation Research Grant; Splenocyte; success; Supportive care; synergism; System; T-Lymphocyte Epitopes; Technology; Testing; Tissues; TLR4 gene; TLR5 gene; TLR9 gene; Toll-like receptors; Toxicology; Vaccinated; Vaccination; Vaccine Antigen; vaccine development; Vaccines; Variant; Viral Antigens; Virus; Virus Activation; Virus Diseases; World Health Organization