Development of thermostable ADDomer vaccines against incurable diseases

Imophoron, a biotech start-up from the University of Bristol, has developed a new class of synthetic vaccines using its next-generation rapid-response vaccine platform. The vaccine platform is based on a self-assembling thermotolerant protein called ADdomer which looks like a virus but does not contain any genetic material. This approach generates new vaccines that can be produced and stored at warmer temperatures, allowing global distribution without the requirement of cold chain storage.

Technological networks
spoke with Jonathan Hare, PhD, Head of Immunology at Imophoron, to learn more about the platform, the benefits of delivering vaccines through various administrative routes, and the infectious diseases they are currently working on to develop vaccines.

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

Jonathan Hare (JH):
Infectious diseases continue to be among the leading causes of preventable death globally and disproportionately affect communities in low- and middle-income countries, especially women and children. Climate change is accelerating many health threats around the world and the intersection of a changing global climate and infectious diseases was a hot topic at the recent COP26 summit.

Finding solutions that can help address these inequalities is part of Imophoron’s ethics and was a major driver in the journey that led to the identification of ADDomer as a vaccine scaffold that had the potential to address many of the challenges faced by the existing vaccine. platform technologies.

ADDomer is a synthetic protein scaffold derived from a component of adenovirus, a widely used vaccine vector. Sixty bases of adenovirus proteins self-assemble in vitro into twelve pentons into a highly stable and versatile dodecahedral viral particle – ADDomer. Each basic protein subunit contains two regions that can be modified to express different protein subunits derived from other pathogens. These regions protrude from the surface of the ADDomer and, as such, can be used for epitope structures specifically functionally relevant to initiate antibody responses as well as being processed by the immune system to prime. cell-mediated immunity. This design-to-manufacture process can be completed in as little as five weeks, making this platform extremely flexible and able to respond to changing requirements with little process adaptation. 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 important differences that sets it apart is its thermostability profile, which overcomes the limitations faced by many communities with countries in ensuring equitable access to vaccines.

The impact of a robust thermostability profile can be most broadly illustrated in the context of access to COVID-19 vaccines available in LMICs. A joint WHO / UNICEF report in 2016 estimated that 98% of all health facilities in LMICs had no cold chain infrastructure or were compromised, which may limit the capacity of health centers to provide vaccines to the community. The lack of a cold chain has been a challenge for the administration of the Pfizer / BioNTech COVID vaccine which frequently requires cold storage at temperatures

Additional advantages revolve around the ease of manufacture using existing recombinant protein expression technologies. This has significant advantages around the requirement to demonstrate 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 relates to 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 current vaccine distribution platforms in addressing global inequalities in vaccine access.

LL: Your vaccines allow delivery through different administrative channels. What are the main benefits of “changing” the route of vaccine administration?

The route of vaccine administration may affect the location of the vaccine which may, in turn, influence the priming of immune cells and impact local and systemic immune responses. The majority of available vaccines are administered by intramuscular (IM) injection, some being administered either subcutaneously (SC) or intradermally (ID). All three methods require trained personnel to administer the vaccination and while ID immunization frequently generates stronger immune responses than IM and SC injection, there may be more serious local adverse effects. As such, IM and SC deliveries are the most common. Mucosal administration of the vaccine is less widely used despite some notable advantages, including the induction of local immune responses at the primary site of infection and the fact that administration can be performed autonomously. In 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 prevention of infections and subsequent transmission of respiratory infections.

Studies are underway to confirm these results, but if they are reproducible, it 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. The combination of self-administration with the thermostability profiles that suggest that ADDomer vaccines can be stored without old storage offers the possibility of developing vaccines that can have a significant impact on global health issues across a wide variety of conditions. ‘viral infections, including
respiratory syncytial virus (RSV).

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

The inventors of ADDomer and its derivatives are Frederic Garzoni (CEO of Imophoron) and Professor Imre Berger, both with extensive experience in structural biology and recombinant protein production technology. The production of ADDomer uses a protein expression system favored by large pharmaceutical companies to already produce approved vaccines. In order to study the structure of ADDomer, Imophoron uses electronic cryomicroscopy 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 structure of ADDomer at atomic resolution in record time to advance the design of its candidate vaccines. My role at Imophoron is to complement this expertise with my experience in immunology, to further improve vaccine design and to contribute to future preclinical and clinical studies.

LL: What infectious diseases are you currently focusing on?

Our The current pipeline is focused on developing vaccines to combat Respiratory Syncytial Virus and Chikungunya Virus which impose significant health burdens on these communities and demographics. RSV infection is responsible for 70% of bronchitis in children under one year of age and also contributes significantly to morbidity and mortality in the elderly, the immunocompromised and those with chronic cardiopulmonary disease. The Chikungunya virus infects millions of people each year, with major implications for global public health, as the incidence rate and geographic extent have increased dramatically over the past 50 years as populations expand vectors, increased global travel and trade, population growth, rapid and unplanned urbanization, and climate change. Further spread of Chikungunya and other related arboviruses is expected due to projected changes in demographic and economic factors, climate, and the natural environment, with the majority of the associated health burden falling on LMICs.

Jonathan Hare spoke to Laura Elizabeth Lansdowne, editor-in-chief of Technology Networks.

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