Iaso Therapeutics is dedicated to developing next generation vaccines to enhance human health and treat diseases.
Vaccines have protected humankind from many deadly infections including smallpox, yellow fever, and tetanus, saving millions of lives. However, the rampage of the COVID-19 over the world serves as a painful reminder of the lack of effective vaccines against many other diseases. Novel technologies that can be readily deployed for new vaccines, especially against newly emerged pathogens, are urgently needed.
A significant roadblock in developing effective vaccines is the low immunogenicities of antigens for subunit vaccines. Carrier moieties are essential to conjugate with the subunit antigen, deliver the antigen to the immune cells, and to activate the immune system. However, there are only limited choices of carriers for clinical uses, which include CRM-197, tetanus toxoid, and keyhole limpet hemocyanin (KLH). With the increases in types of vaccines being developed clinically, more and more conjugate vaccines are sharing the same carrier, which can interfere with each other. Therefore, a powerful new carrier can be extremely valuable to expand the arsenal of vaccines.
Our company has developed a proprietary mutant bacteriophage Qβ (mQβ) platform technology. Head to head comparison studies of against those using the benchmark carriers have shown that our mQβ conjugates can elicit more powerful immune responses. This exciting technology is being applied to vaccines against a variety of diseases including cancer and microbial infections.
To benchmark the superiority of mQβ platform, we have performed head-to-head comparison studies of mQβ against CRM-197, KLH, and TT using a tumor associated carbohydrate antigen (TACA). The carbohydrate (glycan) antigen was conjugated with mQβ and the three benchmark carriers CRM-197, KLH and TT respectively. Anti-glycan IgG generated from immunized mice was analyzed by ELISA on day 35 after the first immunization. As shown in the Figure, the mQβ-glycan conjugate induced significantly higher average anti-glycan IgG titers than the groups of mice immunized with CRM-197-glycan, KLH-glycan and TT-glycan conjugates.
Rashidijahanabad, Z.; Kelly, M.; Kamruzzaman, M.; Qadri, F.; Bhuiyan, T. R.; McFall-Boegeman, H.; Wu, D.; Piszczek, G.; Xu, P.;* Ryan, E. T.;* Huang, X.* “Virus like particle display of Vibrio cholerae O-specific polysaccharide as a potential vaccine against cholera” ACS Infect. Dis. 2022, in press.
Sungsuwan, S.; Wu, X.; Kavunja, H.; McFall-Boegeman, H.; Lang, S.; Rashidijahanabad, Z.; Nick, S. T.; Shaw, V.; Yin, Z.; Jin, X.*; Huang, X.* “Structure Guided Design of Bacteriophage Qβ Mutants as Next Generation Carriers for Conjugate Vaccines” ACS Chem. Biol., 2022, in press.
Wu, X.; Ye, J.; Kavunja, H.; DeLaitsch, A.; Rashidijahanabad, Z.; Lang, S.; Kakeshpour, T.; Zhao, Y.; Ramadan, S.; Vilar Saavedra, P.; Yuzbasiyan-Gurkan, V.; Cao, H.*; Gildersleeve, J. C.*; Huang, X.* “Chemoenzymatic Synthesis of 9NHAc-GD2 Antigen to Overcome Hydrolytic Instability of O-Acetylated-GD2 for Anticancer Conjugate Vaccine Development” Angew. Chem. Int. Ed. 2021, 60, 24179-24188.
Wu, X.; McFall-Boegeman H.; Rashidijahanabad, Z.; Liu, K.; Pett, C.; Yu, J.; Schorlemer, M.; Ramadan, S.; Behren, S.; Westerlind, U.; Huang, X.* “Synthesis and Immunological Evaluation of the Unnatural β-linked Mucin-1 Thomsen-Friedenreich Conjugate” Org. Biomol. Chem. 2021, 19, 2448-2455
Wang, P.; Huo, C.-X.; Lang, S.; Caution, K.; Nick, S. T.; Dubey, P.; Deora, R.;* Huang, X.* “ Chemical Synthesis and Immunological Evaluation of a Pentasaccharide Bearing Multiple Rare Sugars as a Potential Antipertussis Vaccine.” Angew. Chem. Int. Ed. 2020, 59, 6451–6458. Highlighted in Synfacts 2020, 16, 0471. https://www.thieme-connect.com/products/ejournals/pdf/10.1055/s-0040-1707573.pdf
Dhara, D., Baliban, S. M.; Huo, C.-X.; Rashidijahanabad, Z.; Sears, K. T.; Nick, S. T.; Misra, A. K.;* Tennant, S. M.;* Huang, X.* “Syntheses of Salmonella Paratyphi A Associated Oligosaccharide Antigens and Development towards Anti-Paratyphoid Fever Vaccines.” Chem. Eur. J. 2020, 26, 15953-15968.
Wu. X.; McKay, C.; Pett, C.; Yu, J.; Schorlemer, M.; Ramadan, S.; Lang, S.; Westerlind, U.; Finn, M. G.; Huang, X.* “Synthesis and Immunological Evaluation of Disaccharide Bearing MUC‑1 Glycopeptide Conjugates with Virus-like Particles.” ACS. Chem. Biol. 2019, 14, 2176-2184. This work has been highlighted as the cover of the issue. https://pubs.acs.org/pb-assets/images/_journalCovers/acbcct/acbcct_v014i010.jpg?0.6312907862471471
Huo, C.-X.; Dhara, D., Baliban, S. M.; Nick, S. T.; Tan, Z.; Simon, R.; Misra, A. K.; Huang, X.* “Synthetic and immunological studies of Salmonella Enteritidis O-antigen tetrasaccharides as potential anti-Salmonella vaccines.” Chem. Commun. 2019, 55, 4519-4522.
Wu. X.; Yin, Z.; McKay, C.; Pett, C.; Yu, J.; Schorlemer, M.; Gohl, T.; Sungsuwan, S.; Ramadan, S.; Baniel, C.; Allmon, A.; Das, R.; Westerlind, U.; Finn, M. G.; Huang, X.* “Protective Epitope Discovery and Design of MUC1-based Vaccine for Effective Tumor Protections in Immunotolerant Mice.” J. Am. Chem. Soc. 2018, 140, 16596-16609.
Yin, Z.; Wu. X.; Kaczanowska, K.; Sungsuwan, S.; Comellas-Aragones, M.; Pett C., Yu J.; Baniel, C.; Westerlind, U.; Finn, M. G.; Huang, X.* “Antitumor Humoral and T Cell Responses by Mucin‑1 Conjugates of Bacteriophage Qβ in Wild-type Mice.” ACS Chem. Biol. 2018, 13, 1668-1676.
Yin, Z.; Dulaney, S.: McKay, C. S.; Baniel, C.; Kaczanowska, K.; Ramadan, S.; Finn, M. G.; Huang, X.* “Chemical Synthesis of GM2 Glycans, Bioconjugation with Bacteriophage Qb, and the Induction of Anticancer Antibodies.” ChemBiochem 2016, 17, 174-180.
Yin, Z.; Chowdhury, S.; McKay, C.; Baniel, C.; Wright, W. S.; Bentley, P.; Kaczanowska, K.; Gildersleeve, J. C.; Finn, M. G.; BenMohamed, L.; Huang, X.* “Significant Impact of Immunogen Design on the Diversity of Antibodies Generated by Carbohydrate-Based Anticancer Vaccine.” ACS Chem. Biol. 2015, 10, 2364-2372. This work has also been highlighted in the October 2015 POD cast from ACS Chemical Biology. http://pubs.acs.org/page/acbcct/audio/index.html
Yin, Z.; Comellas-Aragones, M.; Chowdhury, S.; Bentley, P.; Kaczanowska, K.; BenMohamed, L.; Gildersleeve, J. C.; Finn, M.G.*; Huang, X.* “Boosting Immunity to Small Tumor-Associated Carbohydrates with Bacteriophage Qβ Capsids.” ACS Chem. Biol. 2013, 8, 1253-1262.
This work has been highlighted by Chemical & Engineering News,
as well as in the June 2013 POD cast from ACS Chemical Biology.