ABV-103*Anti-Marburg virus disease Therapeutic*

ABV-103 is a humanized macaque-derived monoclonal antibody with potent and broad neutralizing activity toward all strains of Marburg and Ravn viruses. ABV-103 has provided protection against lethal challenge with these viruses in animal models including gold standard nonhuman primates. ABV-103 is currently at the IND-enabling stage under a NIAID funded program.

Relevant publications for IBT-T02:

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. Immunization-Elicited Broadly Protective Antibody Reveals Ebolavirus Fusion Loop as a Site of Vulnerability. Cell. 2017 May 18;169(5):891-904.e15. doi: 10.1016/j.cell.2017.04.038. PMID: 28525756; PMCID: PMC5803079.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5803079/

Brannan JM, He S, Howell KA, Prugar LI, Zhu W, Vu H, Shulenin S, Kailasan S, Raina H, Wong G, Rahim MN, Banadyga L, Tierney K, Zhao X, Li Y, Holtsberg FW, Dye JM, Qiu X, Aman MJ. Post-exposure immunotherapy for two ebolaviruses and Marburg virus in nonhuman primates. Nat Commun. 2019 Jan 10;10(1):105. doi: 10.1038/s41467-018-08040-w. PMID: 30631063; PMCID: PMC6328579.

https://journals.asm.org/doi/full/10.1128/mBio.01438-20

IBT-T02 *Pan-Ebolavirus Therapeutic*

IBT-T02 is a cocktail of two monoclonal antibodies with potent neutralizing activity against Ebola, Sudan, and Bundibugyo viruses. IBT-T02 has provided full protection against lethal challenge with these viruses in nonhuman primates, ferrets, guinea pigs, and mice. IBT-T02 is currently at the IND-enabling stage.

Relevant publications for IBT-T02:

ZZhao 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. Immunization-Elicited Broadly Protective Antibody Reveals Ebolavirus Fusion Loop as a Site of Vulnerability. Cell. 2017 May 18;169(5):891-904.e15. doi: 10.1016/j.cell.2017.04.038. PMID: 28525756; PMCID: PMC5803079.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5803079/

ABV-103*Anti-Marburg virus disease Therapeutic*

ABV-103 is a humanized macaque-derived monoclonal antibody with potent and broad neutralizing activity toward all strains of Marburg and Ravn viruses. ABV-103 has provided protection against lethal challenge with these viruses in animal models including gold standard nonhuman primates. ABV-103 is currently at the IND-enabling stage under a NIAID funded program.

Influenza Monoclonal Antibody

AbVacc in collaboration with Abviro, LLC has developed a pan-influenza A monoclonal antibody with broad heterosubtypic effective treatment for both Group 1 and 2 influenza A viruses regardless of group specificity, without inducing virus resistance.

This project has currently selected a stable CHO clone for antibody production. Antibody purified from this clone will be evaluated in a number of Influenza strains including high path AI (HPAI) followed by studies to support IND submission.

ABV-104: S. aureus monoclonal antibody cocktail

Invasive Staphylococcus aureus (SA) infections are a major driver of morbidity and mortality in hospital settings and in the community. Growing antimicrobial resistance among SA strains make development of non-antibiotic treatments such as immunotherapy as adjunct therapeutics a pressing need. In collaboration with Eliteimmune, Inc., AbVacc has developed a strong portfolio of highly potent antibodies against key toxins, superantigens, and other virulence factors of S. aureus. A cocktail of these antibodies is being evaluated against several life-threatening syndromes of S. aureus infections.

Relevant publications for ABV-104:

https://pubmed.ncbi.nlm.nih.gov/35730685/

Cd-ISTAb - ISTAb against Clostridium difficile infection

ISTAb, neutralizing antibody cocktail against TcdB engineered to target to the surface of C. difficile to achieve both neutralization and bacterial clearance for treatment of CDI.

Cd-ISTAb is an engineered antibody for treatment of C. difficile infections (CDI). The strategy is based on a novel technology that uses Infection Site Targeted neutralizing anti-toxin Antibodies (ISTAb). ISTAbs are directed to the site of infection through specific phage-derived cell wall targeting (CWT) domains that bind specific bacterial species. Cd-ISTAb integrates toxin neutralization and effector functions into a single therapeutic.

ISTAbs unique properties:

• - Accumulate at the site of infection through binding to the bacteria,
• - Capturing and sequester the toxins as they are released, thereby immediately neutralizing their immune suppressive and tissue destructive effects and prevent toxemia.
• - As the Fc receptor binding sites in the ISTAbs remain intact, ISTAbs mediate opsonophagocytic killing, thus providing a means for concurrent toxin neutralization and bacterial clearance.

Cd-ISTAb is a cocktail of two potent antibodies that neutralize C. difficile Toxin A (TcdA and TcdB) and are targeted to the surface of bacteria.

Ba-ISTAB – ISTAb against Bacillus anthracis

ISTAb, an anti-PA neutralizing antibody targeted to the surface of B. anthracis to achieve both neutralization and bacterial clearance for treatment of Inhalation Anthrax

Ba-ISTAb is an engineered antibody for treatment of infections caused by Bacillus anthracis. The strategy is based on novel technology that uses Infection Site Targeted neutralizing anti-toxin Antibodies (ISTAb). ISTAbs are directed to the site of infection through specific phage-derived cell wall targeting (CWT) domains that bind specific bacterial species. Ba-ISTAb integrates toxin neutralization and effector functions into a single therapeutic.

ISTAbs unique properties:

• - Accumulate at the site of infection through binding to the bacteria,
• - Capturing and sequester the toxins as they are released, thereby immediately neutralizing their immune suppressive and tissue destructive effects and prevent toxemia.
• - As the Fc receptor binding sites in the ISTAbs remain intact, ISTAbs mediate opsonophagocytic killing, thus providing a means for concurrent toxin neutralization and bacterial clearance.

Ba-ISTAb is a fusion of a B. anthracis specific CWT with a potent monoclonal antibody that neutralize Anthrax toxin (PA)

IBT-V02 – Multivalent toxoid vaccine against Staphylococcus aureus infections

Rationally designed 5-component toxoid vaccine against pore-forming toxins and superantigens for prevention of S. aureus skin and skin structure infections (SSSI)

IBT-V02 is a multivalent toxoid vaccine indicated for prevention of recurrent skin infections caused by Staphylococcus aureus. IBT-V02 is the only entirely toxoid vaccine for S. aureus currently under development. IBT-V02 is being developed under a grant from CARB-X and NIAID and funding from Novo Holdings. The vaccine is scheduled to enter phase I safety and immunogenicity trial in 2023. IBT-V02 differentiates from other prior efforts for S. aureus vaccine in multiple ways.

• ● Differentiator- Mechanism of Action: The toxoid vaccine is unique as it circumvents the problem that have plagued previous S. aureus candidate vaccine candidates, all of which targeted the surface of S. aureus. Animal studies and evidence from clinic indicate that targeting the surface of S. aureus can lead to a deleterious immune response while toxoid vaccines are protective.
• ● Differentiator- Supported by clinical ad epidemiological evidence: IBT-V02 is the only S. aureus candidate heavily supported by clinical and epidemiological evidence. Previous vaccine efforts relied on very limited efficacy studies in mice.
• ● Differentiator- Animal efficacy: IBT-V02 has demonstrated remarkable efficacy in eight different animal models in mice and rabbits.

Related publications:

Karauzum H, Venkatasubramaniam A, Adhikari RP, Kort T, Holtsberg FW, Mukherjee I, Mednikov M, Ortines R, Nguyen NTQ, Doan TMN, Diep BA, Lee JC, Aman MJ. IBT-V02: A Multicomponent Toxoid Vaccine Protects Against Primary and Secondary Skin Infections Caused by Staphylococcus aureus. Front Immunol. 2021 Mar 10;12:624310. doi: 10.3389/fimmu.2021.624310. PMID: 33777005; PMCID: PMC7987673.

https://pubmed.ncbi.nlm.nih.gov/33777005/

Venkatasubramaniam A, Liao G, Cho E, Adhikari RP, Kort T, Holtsberg FW, Elsass KE, Kobs DJ, Rudge TL Jr, Kauffman KD, Lora NE, Barber DL, Aman MJ, Karauzum H. Safety and Immunogenicity of a 4-Component Toxoid-Based Staphylococcus aureus Vaccine in Rhesus Macaques. Front Immunol. 2021 Feb 25;12:621754. doi: 10.3389/fimmu.2021.621754. PMID: 33717122; PMCID: PMC7947289. Kailasan S, Kort T, Mukherjee I, Liao GC, Kanipakala T, Williston N, Ganjbaksh N, Venkatasubramaniam A, Holtsberg FW, Karauzum H, Adhikari RP, Aman MJ. Rational Design of Toxoid Vaccine Candidates for Staphylococcus aureus Leukocidin AB (LukAB). Toxins (Basel). 2019 Jun 14;11(6):339. doi: 10.3390/toxins11060339. PMID: 31207937; PMCID: PMC6628420.

https://www.frontiersin.org/articles/10.3389/fimmu.2021.621754/full

Venkatasubramaniam A, Adhikari RP, Kort T, Liao GC, Conley S, Abaandou L, Kailasan S, Onodera Y, Krishnan S, Djagbare DM, Holtsberg FW, Karauzum H, Aman MJ. TBA225, a fusion toxoid vaccine for protection and broad neutralization of staphylococcal superantigens. Sci Rep. 2019 Mar 1;9(1):3279. doi: 10.1038/s41598-019-39890-z. PMID: 30824769; PMCID: PMC6397225.

https://pubmed.ncbi.nlm.nih.gov/30824769/

Kailasan S, Kort T, Mukherjee I, Liao GC, Kanipakala T, Williston N, Ganjbaksh N, Venkatasubramaniam A, Holtsberg FW, Karauzum H, Adhikari RP, Aman MJ. Rational Design of Toxoid Vaccine Candidates for Staphylococcus aureus Leukocidin AB (LukAB). Toxins (Basel). 2019 Jun 14;11(6):339. doi: 10.3390/toxins11060339. PMID: 31207937; PMCID: PMC6628420.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6628420/

Nipah vaccine

In collaboration with University of Texas Medical Branch (UTMB), AbVacc is developing a recombinant vesicular stomatitis virus (VSV)-based vaccine against Nipah virus (NiV), which causes febrile encephalitis and severe respiratory disease in humans with a fatality rate as high as 60-100% in human outbreaks (Malaysia, Bangladesh).

Pre-clinical work showed protection by vaccine lead candidate with a single dose against more pathogenic NiVB (Bangladesh) strain in rodent disease model. AbVacc is currently developing a manufacturing stable cell line for production of the VSV-based NiVB vaccine, which will be further evaluated in nonhuman primate disease model. This work is currently supported by NIH.

NiV is classified as a BSL-4 pathogen because of the high mortality rates associated with infection, the lack of effective medical countermeasures, and the ease of transmission. Additionally, it was also included in WHO’s 2018 List of Priority Pathogens for possible concern of misuse and by CDC as a Tier 1 Select Agent due to rising concerns with respiratory pathogens post COVID-19.

Related Publications:

Geisbert JB, Borisevich V, Prasad AN, Agans KN, Foster SL, Deer DJ, Cross RW, Mire CE, Geisbert TW, Fenton KA. An Intranasal Exposure Model of Lethal Nipah Virus Infection in African Green Monkeys. J Infect Dis. 2020 May 11;221(Suppl 4):S414-S418. doi: 10.1093/infdis/jiz391. PMID: 31665362; PMCID: PMC7213566.

https://pubmed.ncbi.nlm.nih.gov/31665362/

Filovirus vaccine

Using structure-based rational design, AbVacc is developing a pan-filovirus vaccine against hemorrhagic fevers caused by viruses such as Ebola, Sudan, Bundibugyo, and Marburg. Over the past several years, AbVacc and others have identified several broadly neutralizing antibodies against the filovirus glycoprotein. Using the epitope information, AbVacc has set up an iterative design building process to develop and identify a lead pan-filovirus vaccine candidate which shows protection in rodent and nonhuman primate filovirus disease models. AbVacc is in the lead optimization stage for this project.

The 2014 West African Ebola epidemic has caused over 11,000 deaths. The only approved vaccine is specific to the Zaire species of Ebola, while there are additional species of Ebola as well as the related Marburg virus that can cause fatal disease in humans. Considering the unpredictable nature of future filovirus outbreaks, the development of a pan-filovirus vaccine that would broadly protect against multiple filoviruses is critically important.

Our collaborators include The Scripps Research Institute, La Jolla Institute for Immunology, Integral Molecular, USAMRIID, and NEIDL.

Related Publications:

Zhao, Xuelian et al. “Immunization-Elicited Broadly Protective Antibody Reveals Ebolavirus Fusion Loop as a Site of Vulnerability.” Cell vol. 169,5 (2017): 891-904.e15. doi:10.1016/j.cell.2017.04.038

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5803079/

Howell, Katie et al. “Cooperativity Enables Non-neutralizing Antibodies to Neutralize Ebolavirus.” Cell Rep. 2017 Apr 11; 19(2): 413–424. doi: 10.1016/j.celrep.2017.03.049

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082427/

Brannan, J.M., He, S., Howell, K.A. et al. Post-exposure immunotherapy for two ebolaviruses and Marburg virus in nonhuman primates. Nat Commun 10, 105 (2019).

https://doi.org/10.1038/s41467-018-08040-w