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Developing Temperature-Stable ADDomer Vaccines for Untreatable Diseases

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Imophoron, a Bristol University biotech start-up, has developed a novel class of synthetic vaccine using its next-generation rapid-response vaccine platform. The vaccine platform relies on a self-assembling thermotolerant protein called ADDomer which resembles a virus but contains no genetic material. This approach generates novel vaccines that can be produced and stored at warmer temperatures, allowing for global distribution with no requirement for cold chain storage.

Technology Networks
spoke with Jonathan Hare, PhD, Imophoron’s Head of Immunology, to learn more about the platform, the benefits of administering vaccines by a variety of administrative routes and the infectious diseases they are currently working to develop vaccines for.

Laura Lansdowne (LL): Can you tell us more about your next-generation rapid-response vaccine platform ADDomer™?

Jonathan Hare (JH):
Infectious diseases continue to rank among the paramount causes for preventable death worldwide and disproportionately affect communities in low- and middle-income countries particularly women and children. Climate change is accelerating many of the health threats around the world and the intersection of a changing global climate and infectious diseases has been a hot topic at the recent COP26 summit.

Pursuing solutions that can help address these inequities is part of the ethos at Imophoron and has been a big driver in the journey that led to the identification of the ADDomer as a vaccine scaffold that had the potential to address many of the challenges faced by existing vaccine platform technologies.

The ADDomer is a synthetic protein scaffold derived from a component of Adenovirus, a widely used vaccine vector. Sixty base adenovirus proteins self-assemble in vitro into twelve pentons into a highly stable, versatile dodecahedral virus-like particle – the ADDomer. Contained with each base protein subunit are two regions that can be engineered to express different protein sub-units derived from other pathogens. These regions protrude from the surface of the ADDomer and as such can be used to expressly functionally relevant epitope structures for priming antibody responses as well as being processed by the immune system to prime cellular mediated immunity. This process of design to manufacture can be achieved in as little as five weeks which makes this platform extremely flexible and able to respond to changing requirements with little adaptation to the process. This flexibility has been demonstrated in an upcoming publication describing the development of a COVID vaccine candidate alongside our previously described Chikungunya vaccine candidate.

LL: What sets ADDomer apart from other existing platforms? 

One of the most significant differences which set this apart is its thermostability profile, which overcomes the limitations faced by many communities with countries of ensuring equitable access to vaccines.

The impact of a robust thermostability profile can be most widely illustrated in the context of access to available COVID-19 vaccines in LMICs. A joint report from WHO/UNICEF in 2016 estimated that 98% of all health care facilities in LMIC had either no or compromised cold chain infrastructure which can limit the ability of health centers to deliver vaccines to the community. The lack of cold chain has been a challenge for administering the Pfizer/BioNTech COVID vaccine which frequently requires cold storage at temperatures < -70 °C. Although the other COVID vaccines (AZ, Sputnik V, Sinovac, Moderna, Novavax) require less extreme temperature storage (4 °C to -20 °C). A vaccine platform that is stable at ambient temperatures would have a significant impact? on vaccine distributions. Our aim is for ADDomer to meet this need.

Additional advantages revolve around the ease of manufacturing using existing recombinant protein expression technologies. This has significant advantages around the requirement for demonstrating product purity and downstream processing, resulting in a faster and more robust platform that can easily be adapted to meet changing requirements.

The final advantage of the ADDomer platform is linked to the current observations that the vaccine may not need external adjuvants in the final product and/or induce anti-vector immune responses.

Taken together these are all encouraging signs that the ADDomer platform can offer significant advantages over many of the current vaccine delivery platforms in addressing global inequities in vaccine access.

LL: Your vaccines enable delivery via a variety of administrative routes. What key benefits are there to “changing up” the route of vaccine administration?

The route of vaccine administration can affect the vaccine localization that may, in turn, influence the priming of immune cells and impact both local and systemic immune responses. The majority of available vaccines are administered through intramuscular (IM) injection with some administered either subcutaneous (SC) or intradermally (ID). All three methods require trained staff to administer the vaccination and while ID immunization frequently generates greater immune responses than IM and SC injection there can be more serious local adverse reactions. As such IM and SC delivery are the most common. Mucosal vaccine administration is less widely used despite there being some noticeable benefits including induction of local immune responses at the primary site of infection and that delivery can be done autonomously. At Imophoron we have shown in preclinical studies that intranasal immunization with an ADDomer induces systemic antibody responses comparable to IM administration while simultaneously inducing strong antibody responses in nasal mucosal samples, a prerequisite for preventing infection and onward transmission of respiratory infections.

Studies are ongoing to confirm these findings, but if they are reproducible this would indicate that intranasal ADDomer vaccination could be used to combat systemic diseases in addition to respiratory viruses and that self-administration may be possible. Combining self-administration with the thermostability profiles that suggest that ADDomer vaccines can be kept without old storage offers the possibility of developing vaccines that can meaningfully impact global health challenges across a wide variety of viral infections including
respiratory syncytial virus (RSV).

LL: Can you highlight some of the key techniques that were used to develop ADDomer?

Inventors of the ADDomer and its derivatives include Frederic Garzoni (CEO of Imophoron) and Prof. Imre Berger, both have a long experience in structural biology and recombinant protein production technology. The production of the ADDomer uses a protein expression system favored by big pharma to produce approved vaccines already. In order to study the structure of the ADDomer, Imophoron is using cryo-electron microscopy through a collaboration with the University of Bristol, combined with cloud computing provided by Oracle. It is thanks to the combination of these different techniques that Imophoron was able to study the ADDomer structure at atomic resolution in record time to advance the design of its vaccine candidates. My role at Imophoron is to complement this expertise with my immunology background, to further improve vaccine designs and contribute to future preclinical and clinical studies.

LL: What infectious diseases are you currently focusing on?

Our current pipeline is focused on developing vaccines to combat respiratory syncytial virus and Chikungunya virus that inflict significant health burdens on these communities and demographics. RSV infection accounts for 70% bronchitis in children under one-year-old and is also a significant contributor to morbidity and mortality in the elderly, in the immune-compromised and people with chronic cardiopulmonary disease.  Chikungunya virus infects millions of people annually, causing major implications for global public health with the incidence rate and geographic range increasing dramatically over the last 50 years under the effect of expanding vector populations, increasing global travel and trade, population growth, rapid and unplanned urbanisation, and climate change. Further spread of Chikungunya and other related arboviruses is predicted as a result of the projected changes in the demographic and economic factors, climate, and natural environment with the majority of the associated health burden falling on LMIC. 

Jonathan Hare was speaking with Laura Elizabeth Lansdowne, Managing Editor for Technology Networks.