OMNIVAX-COVID spike protein: To create vaccine formulations against the SARS-CoV-2 virus, the team included combinations of different antigens derived from the virus Spike protein complex in the modular vaccine. Credit: Wyss Institute at Harvard University.

A team of multidisciplinary scientists including bioengineers, materials-scientists and immunologists at the Wyss Institute has created a novel infection vaccine platform know as OmniVax.The unique biomaterial-based platform works by presenting antigens to the immune system in a controlled and sustained way, using a 3D scaffold containing the antigen that can be injected to mimic an infection under the skin. The OmniVax technology inspired by the work of Professor David Mooney whose research centerd on creating a novel cancer vaccine has been utilized to create a vaccine against urinary tract infections (UTI) amongst other applications.

Most recently, the team at the Wyss Institute have explored its capability for developing a vaccine against SARS-CoV-2, for which they are conducting preclinical tests that have demonstrated positive results thus far.

Technology Networks spoke with Lead Senior Staff Scientist Ed Doherty from the Wyss Institute for Biologically Inspired Engineering at Harvard University, to learn more.

Molly Campbell (MC): Please can you tell us about the history of the OMNIVAX platform and the development of a biocompatible and biodegradable immuno-material-based vaccine?

Ed Doherty (ED): The OmniVax infection technology was based on an older vaccine concept invented in the Mooney Laboratory. The original vaccine technology concept was invented by a graduate student, Omar Ali Ph. D, with professor David Mooney at Harvards School of Engineering and Applied Sciences in 2009. This technology was designed to collect immune cells from a patient, activate them (in vitro) against tumor cells and then re-inject the activated cells to fight the tumor. Our new concept by-passed the removal, expensive cell culture and poor yield upon re-injection by designing a system that could recruit and activate cells all in vivo. The idea was to recruit the cells into a biomaterial, in the initial configuration it was an implanted degradable poly (lactic-co-glycolic acid) (PLGA) foamed polymer, and present AN antigen and adjuvant to activate the cells. The oncology vaccine utilized the patients own tumor cells as the antigen source. This concept was further developed by my team at the Wyss Institute and subsequentially tested in a Phase I Human Clinical Trial to treat Melanoma with the Dana Farber Cancer Institute. The twenty-five-patient trial demonstrated the vaccine was well tolerated and the additional data will be published.

As my team completed preparing for the Phase I melanoma trial, members of the microbiology/virology team asked if our vaccine platform would work with pathogens as antigens to target infectious diseases. We quickly attempted a few pilot studies to demonstrate protection against a bolus injection of E.coli in a sepsis animal model and soon after the infection vaccine project was funded by the Wyss Institute. We opted to use a newly patented version of the system that utilized mesoporous silica rods (MSR) to create the required scaffold structure, which was injectable unlike the PLGA vaccine which was implantable. We continued to develop new vaccines against MRSA, S. pneumonia, Influenza, HIV, K. pneumonia to demonstrate the capabilities of the platform.

The team began to develop other capabilities to support further development and provide more in-depth characterization of the technology. We began to work with business development personnel to generate business models to identify the best applications and to get feedback from key opinion leaders and physicians. Over the last year we have conducted enough planning and strategizing to feel comfortable that we should form a new company based on the OmniVax platform. We hope to finalize funding over the next few months and begin operations in early 2021.

MC: How does the OmniVax platform work?ED: Unlike traditional protein subunit vaccines which have only an antigen injected to elicit the immune response, the OmniVax platform creates a 3D scaffold with the antigen and other factors to mimic an infection under the skin. The vaccination platform uses a biomaterial-based scaffold injected subcutaneously to deliver a growth factor that attracts large concentrations of immature immune cells (dendritic cells) into the structure which contains the target antigen and activating adjuvant. These immune cells are designed to internalize the antigen, activating them and causing them to migrate to the nearest draining lymph node. Once in the lymph node, the activated, or mature, dendritic cell presents the antigen to the B and T cells, creating both a humoral and cellular immune response against the target antigen. The presence of the scaffold combined with recruiting the specific cell type increases the number and quality of the interactions of the immune cells with target antigens and adjuvants. This safely improves the immunogenicity of the antigen, which is the main reason vaccines fail. The efficiency of the vaccination combined with seven days of recruiting immune cells contributes to the increased duration of the response. Both the Mooney lab and the team at the Wyss Institute have demonstrated the mechanism and utility of this platform technology in dozens of peer-reviewed publications, which also describe feasibility in oncology, reproduction and pathogenic applications. There are several publications that demonstrate that the scaffold structure is essential to maximize the immunogenicity of the target antigen.

MC: How does the scaffold extend the time that dendritic cells are exposed to antigens?ED: There are two answers to this question; the first is that we demonstrated that significantly more dendritic cells are exposed to the target antigen and adjuvant due to being recruited into the scaffold structure. Secondly, the dendritic cells are trafficked though the vaccine to the lymph nodes over the course of a seven-day release of the recruiting factor. This increased number of cells exposed to the antigen and adjuvant is amplified by the constant cycle of dendritic cells being recruit, activated and migrating to the lymph nodes over the seven-day release of recruiting factor. This unique feature of OmniVax has consistently demonstrated the technology platforms ability to increase the robustness and durability of target antigens.

MC: Can you discuss the advantages of combining multiple antigens in a single vaccination using simple modular technologies?ED: The ease to which we can add multiple target antigens to our vaccine platform creates two main advantages to addressing infectious diseases. The first would be to create broader coverage by adding a diverse set of antigens specific to that pathogen or pathogen family, increasing the chances of efficacy and provding cross reactivity with similar or mutated pathogens. Currently there are numerous multivalent approved vaccines (i.e. Prevnar, MMRII) on the market but design modifications require significant development and add complexity to the manufacturing process, we believe this wouldnt be the case with OmniVax.

The modularity of our vaccine platform would also be important to address pandemics or other outbreaks, because the ease of incorporation of antigens into the vaccine system can be done quickly and efficiently which allows for rapid deployment. Perhaps the greater advantage of our system is that the design allows the antigen (viral or bacterial) to be prepared separately at time of outbreak, and be added to the other components which have be pre-manufactured and stored in large qualities.

MC: You are currently developing a vaccine to treat recurring UTIs. Can you tell us more about this? What stage of testing has this vaccine reached?ED: The recurring urinary tract infection (rUTI) vaccine incorporates bacterial adhesion protein antigens that target the mechanism E.coli use to adhere to the lining of the urinary tract. The ability to adhere to the urinary tract allows the bacteria to become embedded and very difficult to eliminate with antibiotics. Although the free bacteria can be controlled with antibiotics, each recurrence must be addressed once symptoms occur in the patient. The treatment were proposing should create an immune response that will eliminate the bacteria during subsequent recurrences and ultimately stop the infection by allowing no bacteria to form new protected sites of infection.

Approximately 50% of women will experience a UTI in their lifetime and 10-20% of all women will experience recurrent UTI. In the US each year, three million women have recurring UTI (two or more for 12- month period). UTIs are also a significant cause of morbidity in infant boys and elderly men. An important subgroup is complicated UTIs, including catheter-associated infections, which have high incidence of antibiotic resistance. The potential for UTI vaccine would represents a $1B+ addressable market. Additionally, our vaccine to the E.coli bacteria that causes 80% of all rUTIs had been previously demonstrated to provide protection against E.coli in a sepsis model developed at the Wyss Institute. The vaccine to prevent rUTI has been tested at the Wyss Institute to verify that we can generate antibodies and cellular responses specifically against E. coli bacteria. In addition, we have conducted feasibility studies in an animal model for rUTI developed at the Wyss Institute. Currently we are testing our UTI Vaccine in a program sponsored by the National Institute of Allergies and Infectious Disease (NIAID) in an established and validated rodent model.

We (myself and four other Wyss/Harvard Scientists) are currently raising funds with the intention of starting a new company and complete the preclinical and chemistry. Manufacturing and Controls (CMC) activities that would the filing of an Investigational New Drug (IND) application. This IND would allow us to demonstrate the safety and efficacy of our vaccine platform in Human Clinical trials.

MC: How is the Wyss team applying the OMNIVAX technology for the development of a vaccine for SARS-CoV-2? At what stage is this research?ED: Our work with SARS-CoV-2 began in April when all of the Harvard/Wyss laboratories were shut down except for COVID-related projects. In response to the global crisis and to demonstrate how quickly we can address new pathogen targets three to four of the infection team worked throughout the four-month shut down and made significant progress. We incorporated seven different combinations of COVID related proteins into our vaccine platform and vaccine animals in the first week of the shutdown. We quickly demonstrated the ability generate significantly high antibody titers against the targeted antigen, except one. Based on these results we reached out to collaborators in the Boston area and they were impressed enough to offer antibody neutralization testing, which was also very impressive. We are currently moving to the hamster challenge model to demonstrate efficacy and have applied for grants to support non-human primate studies. Updated efficacy and duration data will be published soon. Much like the rUTI application, we would have to complete the pre-clinical and CMC work to move to human trials, which would be the main focus of the start-up company.

MC: Can you discuss the safety of the OMNIVAX technology?ED: The vaccine platform has consistently generated a very good safety profile in all of the animal studies conducted over the last four years. These studies have evaluated numerous combinations of antigens and adjuvants in a rodent, rabbit, porcine, and bovine animal models. The site of injection, organs and general health of all animals has demonstrated a high degree of safety. The injected vaccine does create a small bump under the skin, which then expands slightly as the immune cells are recruited and fill the scaffold. We sometimes think of this type of vaccine as infection mimicking, so some swelling of the injection site is expected and encouraged. The components are ultimately metabolized and the MSRs degrade and the injection site resolves completely after 25-35 days. The good reactogenicity of our system may be related to the very small doses of both antigens and adjuvants contained within our vaccines. We are able to maximize immunogenicity without increasing the doses of higher reactive components to create a robust response. We are able to rely on the recruitment and cell trafficking to improve potency, not adding more antigen or adjuvant.

The biodegradable MSR material used in our vaccines is made from silica, which is approved for human consumption and utilized in many oral pharmaceuticals. There are numerous human clinical trials that have used silica for imaging or to delivery drugs, however the MSR configuration will are using will have to undergo the normal safety evaluation prior to use in human trials. Based on the 90 studies we have conducted, we have a great deal of confidence that we safety profile will be appropriate for human applications.

MC: What challenges exist when developing a technology such as OMNIVAX in an academic lab?ED: The Wyss Institute provides a unique advantage because they employ industry professionals like me to facilitate the development and de-risking of technologies such as OmniVax. The Wyss Institute hires scientists and engineers from industry to identify technologies and work with faculty to move beyond the academic level develop to a stage that is considerably more likely to be licensed, partnered, or spun out into a start-up company.

The OmniVax team at the Wyss Institute consists of professionals that have backgrounds in cGMP manufacturing, microbiology, immunology, infectious disease, analytical testing, protein chemistry, material science, drug delivery and business development. This team worked very closely with Mooney and his students at Harvards School of Engineering and Applied Sciences to better understand the mechanism and many based science questions. At the same time, the Wyss Institute team was investigating improved characterization methods, material sources, regulatory strategy, animal models, applications, safety profiles and business opportunities required to commercialize the technology. This combination of academic brain power and industry experience used at the Wyss Institute, creates a special atmosphere of collaboration, creativity and translation that enables success. We noticed that there is a chance that the pandemic may have begun to change the minds of many to believe that vaccines are critical for public health.

Ed Doherty was speaking to Molly Campbell, Science Writer for Technology Networks.

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Biomaterial-Based Vaccine That Sits Under the Skin Shows Promise Against SARS-CoV-2 - Technology Networks