Integral Molecular and Integrated BioTherapeutics Initiate Collaboration for Virus Vaccine Discovery

View the article at: http://www.businesswire.com/news/home/20170302005790/en

Integral Molecular and Integrated BioTherapeutics have teamed up in the fight against the global health crises posed by Ebola and Zika viruses, signing a collaborative vaccine discovery agreement to help eradicate these threats.

The two companies will leverage their complementary technologies to produce vaccine candidates that are specifically engineered to generate a maximally protective immune response in humans. The availability of such vaccines will prevent the recurrence of the deadly 2014-2016 Ebola epidemic that killed over 11,000 people in West Africa, and has the potential to curtail the spread of the ongoing Zika virus epidemic associated with severe fetal brain defects.

Integral Molecular is an industry leader in the study of complex membrane proteins such as viral Envelope proteins. The company will use its proprietary Shotgun Mutagenesis protein engineering technology to generate and screen large panels of Envelope protein variants to identify an optimized protein that could serve as a highly immunogenic and protective vaccine, and will ultimately apply its high-resolution epitope mapping technologies to characterize the vaccine’s protective effects. Integrated BioTherapeutics, a leader in infectious disease research, will conduct preclinical studies to test the efficacy of vaccine candidates in disease models.

“The vulnerability of human populations during the recent Ebola and Zika outbreaks highlighted the consequences of the lack of effective vaccines against these pathogens. The goal of our collaboration is to meet these concerns by creating efficacious vaccine candidates based on viral Envelope proteins,” said M. Javad Aman, President and CEO of Integrated BioTherapeutics.

“We look forward to working with Integrated BioTherapeutics. Their experience in the development of a pipeline of antiviral products based on rationally designed and engineered viral proteins and antibodies will be a tremendous asset in our joint efforts towards producing Ebola and Zika vaccines,” continued Benjamin Doranz, President and CEO of Integral Molecular.

Thus far, the two companies have engaged in highly successful collaborative research that has culminated in the pursuit of these vaccine candidates. This includes the development and characterization of the protective and cross-neutralizing pan-Ebola antibody FVM04, recently published in Cell Reports (Howell et al., 2016). Additional research resulting from this collaboration is expected to be published later this year.

About Integral Molecular

Integral Molecular is a research-driven biotechnology company creating innovative technologies and a pipeline of therapeutic antibodies against under-exploited membrane protein targets, including GPCRs, ion channels, transporters, and viral envelopes. This platform is built on the company’s Lipoparticle and Shotgun Mutagenesis technologies and over 15 years of experience optimizing membrane proteins. Integral Molecular discovers antibodies for partners in parallel with its own independent work developing antibodies for licensing. The company currently has therapeutic programs focused on pain, immunity, and infectious diseases. For more information, visit www.integralmolecular.com.

About Integrated BioTherapeutics

IBT is a biotechnology company focused on the discovery of novel vaccines and therapeutics for emerging infectious diseases with a pipeline that includes promising product candidates for bacterial and viral infections including unique pan-filovirus monoclonal antibodies and vaccine candidates and a variety of other engineered product candidates for emerging viruses. IBT also operates a testing service business (www.ibtbioservices.com) focused on in vitro and in vivo models for viral agents such as Zika, dengue, yellow fever, influenza and RSV as wells as bacterial agents such as S. aureusS. pneumoniaeE. Coli, and C. difficile. Located in Rockville, Maryland, IBT has a close working relationship with United States Government agencies including the National Institute of Allergy and Infectious Diseases (NIAID/NIH), National Cancer Institute (NCI), Department of Defense (DOD), United States Army Medical Research Institute of Infectious Diseases (USAMRIID) as well as many biotechnology and pharmaceutical companies and academic laboratories. For more information, visit www.integratedbiotherapeutics.com.

Contacts

Integral Molecular, Inc.
Benjamin Doranz, 215-966-6061
info@integralmolecular.com
or
Integrated BioTherapeutics
M. Javad Aman, 240-454-8940
www.integratedbiotherapeutics.com

Publications

Immunization-Elicited Broadly Protective Antibody Reveals Ebolavirus Fusion Loop as a Site of Vulnerability.  Zhao X, Howell KA, He S, Brannan JM, Wec AZ, Davidson E, Turner HL, Chiang CI, Lei L, Fels JM, Vu H, Shulenin S, Turonis AN, Kuehne AI, Liu G, Ta M, Wang Y, Sundling C, Xiao Y, Spence JS, Doranz BJ, Holtsberg FW, Ward AB, Chandran K, Dye JM, Qiu X, Li Y, Aman MJ.  Cell. 2017 May 18;169(5):891-904.e15. doi: 10.1016/j.cell.2017.04.038.

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Cooperativity Enables Non-neutralizing Antibodies to Neutralize Ebolavirus.  Howell KA, Brannan JM, Bryan C, McNeal A, Davidson E, Turner HL, Vu H, Shulenin S, He S, Kuehne A, Herbert AS, Qiu X, Doranz BJ, Holtsberg FW, Ward AB, Dye JM, Aman MJ.  Cell Rep. 2017 Apr 11;19(2):413-424. doi: 10.1016/j.celrep.2017.03.049.

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Protective efficacy of a novel alpha hemolysin subunit vaccine (AT62) against Staphylococcus aureus skin and soft tissue infections.  Adhikari RP, Thompson CD, Aman MJ, Lee JC.  Vaccine. 2016 Dec 7;34(50):6402-6407. doi:10.1016/j.vaccine.2016.09.061. Epub 2016 Nov 12.
 

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Safety and Immunogenicity of a Parenterally Administered, Structure-Based Rationally Modified Recombinant Staphylococcal Enterotoxin B Protein Vaccine, STEBVax. Chen WH, Pasetti MF, Adhikari RP, Baughman H, Douglas R, El-Khorazaty J, Greenberg N, Holtsberg FW, Liao GC, Reymann MK, Wang X, Warfield KL, Aman MJ. Clin Vaccine Immunol. 2016 Dec 5;23(12):918-925. Print 2016 Dec.
 

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A "Trojan Horse" Bispecific Antibody Strategy for Broad Protection against Ebolaviruses. Wec, A.Z. Nyakatura, E.K. Herbert, A.S. Howell, K.A. Holtsberg, F.W. Bakken, R.R. Mittler, E. Christin, J.R. Shulenin, S. Jangra, R.K. Bharrhan, S. Kuehne, A.I. Bornholdt, Z.A. Flyak, A.I. Saphire, E. Crowe Jr., J.E. Aman, M.J. Dye, J.M. Lai, J.R. Chandran, K. (2016) Science 8(2016). doi: 10.1126/science.aag3267

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Feverish Quest for Ebola Immunotherapy: Straight or Cocktail?  Aman, M.J. Saphire, EO. (2016) Trends Microbiol 10(1016). pii: SD966-842X(16)30049-X

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Zika Virus: A New Animal Model for an Arbovirus.  Aman, M.J. Kashanchi, F. (2016) PLoS Negl Trop Dis 10(5): e0004702. doi:10.1371/journal.pntd.0004702

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Virus-Like Particle Vaccination Protects Nonhuman Primates from Lethal Aerosol Exposure with Marburgvirus (VLP Vaccination Protects Macaques against Aerosol Challenges).  Dye JM, Warfield KL, Wells JB, Unfer RC, Shulenin S, Vu H, Nichols DK, Aman MJ, Bavari S. Viruses. 2016 Apr 8;8(4). pii: E94. doi: 10.3390/v8040094

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Antibody Treatment of Ebola and Sudan Virus Infection via a Uniquely Exposed Epitope within the Glycoprotein Receptor-Binding Site.  Howell KA, Qiu X, Brannan JM, Bryan C, Davidson E, Holtsberg FW, Wec AZ, Shulenin S, Biggins JE, Douglas R, Enterlein SG, Turner HL, Pallesen J, Murin CD, He S, Kroeker K, Vu H, Herbert AS, Fusco ML, Nyakatura EK, Lai JR, Keck ZY, Foung SKH, Saphire EO, Zeitlin L, Ward AB, Chandran K, Doranz BJ, Kobinger GP, Dye JM, Aman MJ. (2016) Cell Reports 15, 1–13.

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Monoclonal antibody therapy for Junin virus infection.  Zeitlin L, Geisbert JB, Deer DJ, Fenton KA, Bohorov O, Bohorova N, Goodman C, Kim D, Hiatt A, Pauly MH, Velasco J, Whaley KJ, Altmann F, Gruber C, Steinkellner H, Honko AN, Kuehne AI, Aman MJ, Sahandi S, Enterlein S, Zhan X, Enria D, Geisbert TW. Proc Natl Acad Sci U S A. 2016 Apr 19;113(16):4458-63.

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Aman MJ, Chasing Ebola through the Endosomal Labyrinth:, MBio, 2016, 7(2):e00346-16

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Holtsberg et al., Pan-ebolavirus and Pan-filovirus Mouse Monoclonal Antibodies: Protection against Ebola and Sudan Viruses, J Virol, 2014

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Keck et al., Macaque Monoclonal Antibodies Targeting Novel Conserved Epitopes within Filovirus Glycoprotein, J Virol, 2014

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Adhikari et al., Antibodies to S. aureus LukS-PV Attenuated Subunit Vaccine Neutralize a Broad Spectrum of Canonical and Non-Canonical Bicomponent Leukotoxin Pairs, PLoS One, 2015

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Fusco et al., Protective mAbs and Cross-Reactive mAbs Raised by Immunization with Engineered Marburg Virus GPs, PLoS Pathog, 2015

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Warfield et al., Homologous and heterologous protection of nonhuman primates by Ebola and Sudan virus-like particles, PLoS One, 2015

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Sully et al., A tripartite cocktail of chimeric monoclonal antibodies passively protects mice against ricin, staphylococcal enterotoxin B and Clostridium perfringens epsilon toxin, Toxicon, 2014

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Warfield et al., Vaccinating captive chimpanzees to save wild chimpanzees, Proc Natl Acad Sci USA, 2014

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Aman and Adhikari, Staphylococcal bicomponent pore-forming toxins: targets for prophylaxis and immunotherapy, Toxins, 2014

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Karauzum et al., Structurally designed attenuated subunit vaccines for S. aureus LukS-PV and LukF-PV confer protection in a mouse bacteremia model, PLoS One, 2013

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Adhikari et al., Lower antibody levels to Staphylococcus aureus exotoxins are associated with sepsis in hospitalized adults with invasive S. aureus infections, J Infect Dis, 2012

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Adhikari et al., Novel structurally designed vaccine for S. aureus α-hemolysin: protection against bacteremia and pneumonia, PLoS One, 2012.

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