Liverpool University spin-out ReNewVax’s goal of creating the first universal pneumococcus vaccine began with extensive library analysis and two decades of research by its parent institution, outlines Marie O’Brien.
The city of Liverpool has a long and proud history of leadership and innovation in infectious disease treatment and prevention. From the opening of the first public baths to combat the cholera epidemic in the 1830s to our city being home to pilot mass testing during the Covid- 19 pandemic and, more recently, as the home of iiCON, the pioneering infection innovation consortium, Liverpool has proven itself to be at the forefront of epidemiology, diagnosis and treatment of infectious diseases that present a persistent threat to global health and prosperity.
Now, our company, ReNewVax – a University of Liverpool spin-out – is harnessing this rich legacy and spirit of invention to create the world’s first universal vaccine for Streptococcus pneumoniae (also known as the pneumococcus), a bacterium which kills more children under the age of five than measles, malaria and HIV-AIDS combined (World Health Organisation).
It is the primary cause of life-threatening diseases such as pneumonia, meningitis and sepsis, resulting in over 1.9 million deaths a year. The Global Burden of Disease Study has estimated that 55% of chest infection deaths are attributable to pneumococcus and it is also a leading cause of death associated with antimicrobial resistance (AMR) globally.
The bacterium exists in at least 100 distinct variants – known as serotypes – which vary in their biological properties and distribution around the globe and spreads through contact with people who carry the bacteria in their nose and throat via respiratory droplets.
Worryingly, people – particularly children and infants – can be carriers without showing any signs of disease, drastically increasing the risk of the infection being passed on, meaning vaccines are the best means to control and prevent pneumococcal disease.
Existing licensed pneumococcal vaccines have been instrumental in reducing the incidence of invasive disease globally. Yet those currently available only offer protection against approximately 20% of the range of around 100 serotypes. Counter-productively, this therefore results in a process known as serotype replacement, which promotes the spread of non-vaccine covered serotypes, leading to variants not susceptible to existing vaccines becoming dominant, and the sustained prevalence of pneumococcal invasive diseases globally. Worse still, these non-susceptible variants are often resistant to existing antibiotics, contributing to the rise of AMR.
This issue is exemplified by published data showing that pneumococcal disease in the EU increased by 41% over a five-year period, despite high levels of vaccination across Europe.
Vaccines for pneumococcus were the largest vaccine market pre-pandemic, with annual sales of around $9.5 billion.
Yet, due to their composition, existing vaccines are complex, expensive to manufacture and have high dosage costs – severely constraining their global use and ability to save lives.
Such limitations, especially when viewed in tandem with the rise of antimicrobial resistance, are driving the need for development of a lower cost vaccine with broader, ideally universal, cross-serotype coverage, with the WHO naming it as one of its priorities.
When the stakes are so high, it is often the case that a total rethink of approach can lead to the success that is so desperately required.
[Pictured below: CEO Dr Neil Murray with Dr Marie O’Brien, Dr Miguel Leon-Rios and Dr Dunhao Su]
The University of Liverpool has led pneumococcal vaccine research for more than 20 years, particularly for the HIV-infected population. For example, studies from our university undertaken during the early 2000s described the large burden of pneumococcal disease, failure of adjunctive therapies to reduce case-fatality and the overwhelming need for preventive vaccination.
Now, expertise harnessed at the university is being deployed to produce the first universal pneumococcus vaccine.
While traditional vaccine development is hypothesis-driven and carries substantial risk until clinical evidence is generated, ReNewVax deploys a rational approach to vaccine development, using analysis of an extensive library of clinical samples, gathered from around the world, to identify protein antigens that can form the basis of an effective vaccine.
Our lead program, RVX-001, is focused on the development of a novel protein-based, universal pneumococcal vaccine.
The protective efficacy and immunogenicity of RVX-001 has been established in murine models of invasive pneumococcal disease (IPD) using both adult and infant mice, and in challenge experiments with vaccine and nonvaccine- covered serotypes.
The well-established Prevnar 13 vaccine (Pfizer) was used as the benchmark throughout our investigations and our results showed that RVX-001 offered cross-serotype protection that Prevnar 13 failed to provide. This effect has been shown to be largely due to proteinspecific cell mediated immune responses.
When the stakes are so high, it is often the case that a total rethink of approach can lead to the success that is so desperately required
As well as our rational design approach, the addition of an extra de-risking step, employing an ex vivo human predictive model to confirm the immunologic properties of our vaccines before they are tested in clinic, increases the likelihood of clinical success.
RVX-001 is designed with antigens common to all pneumococcus serotypes, making it what we hope will be the first universal pneumococcal vaccine.
Importantly, and excitingly, its components can be produced recombinantly, meaning the vaccine will be cheaper to manufacture, as well as being more effective, than those currently available.
With efficacy in animals having already been established, showing a strong immunogenic profile, RVX-001 is now entering IND/CTA enabling studies with a view to moving into clinical trials in early 2025.
In addition to RVX-001, we have two further pipeline programs – RVX-002 focused on Group B Streptococcus and RVX-003 focused on Group A Streptococcus.
Dr Marie O’Brien is Chief Scientific Officer at ReNewVax
