Building Better Vaccines: Iaso Therapeutics
Vaccines have dominated the news. With the COVID-19 pandemic, stories about vaccines have been a daily occurrence. They range from concerns about safety to vaccination rates and distribution. They highlight the amazing science that led to the commercial development of novel technologies. The public has probably heard more about vaccines in recent days than they can remember. With the public’s attention, these news stories also highlight the benefit of new vaccines and can show the need for new, safe, and effective vaccine technologies to prepare us for the next disease threat and to protect us against known diseases that are challenging to treat.
The goal of vaccines is to give the immune system a way to practice its response to a pathogen. Once the immune system has practiced its response, it can remember what to look out for and can more forcefully respond to the pathogen in the future. There are different types of vaccines that can be used to train our immune system. Attenuated vaccines, like the MMR vaccine, are created by using live pathogens but weakening them to reduce their virulence. Inactivated vaccines, like most flu shots, are similar but use a killed pathogen, rather than using a live, weakened form. Subunit vaccines use parts or components of pathogens to trigger an immune response. These vaccines use fragments of pathogens, called antigens, which are then recognized by our immune cells as foreign, triggering our immune response. RNA and DNA vaccines – like the Moderna and Pfizer/BioNTech COVID-19 vaccines – are similar to subunit vaccines, but instead use nucleic acids to encode the pathogen fragments, which are then produced by cells in the body for recognition by our immune cells.
Our immune cells recognize certain antigens on pathogens. But not all antigens trigger a strong immune response on their own. To address this limitation, some vaccine developers link a weak antigen to a strong antigen also known as a carrier molecule. With these conjugate vaccines, the immune cells recognize the strong antigen and mount a forceful response. And because of its tether, the weak antigen is guilty by association, and the immune system learns to respond strongly to the weak antigen as well. As you can imagine, this vaccine approach can be a powerful training tool for our immune system.
However, conjugate vaccines have some limitations. There aren’t an unlimited number of suitable antigen carriers. Relying on limited number of carriers can led to over-usage. If the same carrier is over-used in multiple types of vaccines, it begins to lose its efficacy as the immune response in our bodies will over-respond to the carrier and prevent the vaccine from inducing the desired responses against the antigen. And sometimes, these “strong” antigen carriers might not elicit as strong of an immune response as one may want. These limitations can hinder the effectiveness of these vaccines, limiting their protection.
But one startup is working to break through these limitations. Iaso Therapeutics, a 2018 spinout of Michigan State University, is developing a conjugate vaccine platform technology that it believes can avoid the common limitations of conjugate vaccines and lead to better vaccines for emerging infectious diseases and other diseases, like cancer.
Iaso’s solution stems from the work of Xuefei Huang, a professor of chemistry and biomolecular engineering at Michigan State. His lab developed mQβ, a proprietary bacteriophage technology. Bacteriophage are viruses that infect bacteria and are harmless to humans. mQβ is a mutated form of Escherichia coli (E. coli) virus Qβ, a virus with a highly organized spherical structure that infects E. coli. While bacteriophage are harmless to humans, our immune system can still recognize the virus as foreign and mount a response. The team at Iaso use this adjuvant property of bacteriophage to their advantage, using mQβ to stimulate the host immune system. They then decorated the surface of the bacteriophage with antigens of interest.
The company is currently funded by small business grants from the National Science Foundation and the National Cancer Institute of the NIH. So far, the company has generated promising data demonstrating elevated and prolonged antibody titers in animal models following inoculation with its technology, indicating that the technology can induce a robust immune response.
Bob Forgey, CEO, Iaso Therapeutics
Iaso is developing its technology for a number of infectious diseases and is building on the lessons learned by others. Previously, another company in Europe had tried using a non-mutated form of the bacteriophage as a conjugate for non-validated antigens. They made it to Phase 2 clinical trials before disappearing. While this company may not have successfully commercialized their product, the data from the company’s clinical work demonstrated that the bacteriophage vaccine approach was safe in humans. Iaso’s CEO, Bob Forgey, has learned from that European company’s missteps and believed that combining a novel antigen with the novel vaccine platform in an unproven health condition was a mistake. Therefore, Bob has positioned Iaso to focus on clinically validated antigens with known applicability, pairing these well-characterized antigens with Iaso’s technology to generate better vaccines.
In addition to infectious diseases, Iaso is interested in using its vaccine technology as a potential treatment for cancer. While the concept of a cancer vaccine may seem different from how vaccines are usually described, the overall mechanism would be the same. A cancer vaccine would expose immune cells to a specific antigen – in this case a protein strongly associated with cancer cells – to train the immune cells to recognize and eliminate tumor cells. This could be an important component in the fight against cancer, since tumor cells often have means to avoid detection by the immune system. Iaso Therapeutics currently has a small business grant from the National Cancer Institute to investigate its mQβ platform for targeting Muc-1, a protein that is overexpressed in certain cancer cells and has been targeted by potential vaccines in the past.
Because this platform could be broadly used, the company is exploring its potential to generate both prophylactic vaccines and therapeutic vaccines. With prophylactic vaccines, the goal is to prevent a disease, and Iaso is testing its vaccine platform against COVID-19 and as a typhoid vaccine by targeting salmonella. With therapeutic vaccines, the objective would be to train or modulate the immune system to treat an ongoing disease. The cancer vaccines would fall into this category, as would vaccines that would treat diseases like Type 2 diabetes.
The Iaso team is convinced of the potential of their platform, and they recognize that they can’t develop vaccines for everything by themselves. So, Bob created a hybrid business model where Iaso develops some vaccines in-house, while sublicensing the platform to other vaccine developers for other diseases and conditions. Bob believes that Iaso’s technology could be useful in cardiovascular diseases, neurodegenerative conditions, and even in animal health applications. To that end, Iaso has generated a variety of mutated bacteriophage types, each with different properties which may be well-suited for specific uses. Iaso already has a partner for the non-clinical research market, where the technology can be used as a valuable research tool.
As COVID-19 has shown us, the world is going to need new vaccines. According to Iaso, the vaccine market is expected to grow, with the global market for conjugate vaccines is expected to reach $20.4 billion by 2024. Bob and the Iaso team are convinced that their technology could play an important part in that market opportunity. In addition to looking for sublicensing partners, the company is preparing for its first investment round which will fund the preclinical testing of its vaccine products, scale up its manufacturing, and move the technology closer to clinical development.
Perhaps one day, Iaso Therapeutics and its products will be regularly making the news as they develop new ways to treat and prevent diseases that affect too many of our lives.
Special thanks to:
Robert Forgey, CEO, Iaso Therapeutics (rforgey@iasotherapeutics.com)
QIAGEN and Todd Festerling, PhD for sponsoring the blog