The Infection Innovation Consortium: iiCON and partners have launched the first human challenge trial for a new vaccine for pneumococcal disease – marking a key milestone in a collaborative global project that is offering new hope in the fight against the disease.
iiCON has reached a key stage in its collaboration with UK SME ImmunoBiology Ltd (ImmBio) to bring forward a new vaccine, PnuBioVax, against pneumococcal disease, a leading preventable cause of death in children. The consortium, which is led by Liverpool School if Tropical Medicine, is leading the delivery of the £3.2 million Medical Research Council (MRC) funded trial for the disease, which has high rates of antibiotic resistance, and is a major cause of disease globally.
The programme has now reached a key milestone as it launches the first trials of the vaccine in people in Malawi. The trial will enrol 400 people and will be the biggest human challenge trial conducted in the country to date.
Invasive pneumococcal disease, which can vary from mild ear infection to severe sepsis, meningitis and pneumonia, is a global concern, with most child deaths occurring in low- and middle-income countries (LMICs). This has remained the case despite the development of successful vaccines that are effective against the strains of the disease that cause invasive pneumococcal disease in many developed countries.
Streptococcus pneumoniae, the bacteria responsible for pneumococcal disease has nearly 100 different strains, or serotypes; each has a different coating and causes different symptoms, some more serious than others. Current vaccines target the sugars on these outer coatings meaning that they need to be engineered to be specific for each serotype. However, the PnuBioVax vaccine targets proteins which are common across all pneumococcus serotypes, including Serotype 3 pneumococcus (SPN3) a strain responsible for a rise in prevalence of invasive disease, potentially leading to a more holistic control response across many different strains of the disease.
SPN3 is the most common cause of severe pneumonia in children in Europe. It is also treated with the PCV13(1) vaccine and is increasingly becoming resistant to the current vaccine.
UK SME ImmBio developed PnuBioVax and successfully conducted Phase I safety and immunogenicity studies. iiCON has since collaborated with ImmBio to lead on the next phase of development of the vaccine, to bring it to Phase 2 clinical trials.
iiCON led on a grant application to secure MRC funding for the next phase of development. The iiCON/ImmBio team identified a new manufacturer, Recipharm Advanced Bio, to develop the vaccine to the stringent Good Manufacturing Practice (GMP) global health and safety standards required for clinical trials and managed the process from beginning to end. The iiCON team then prepared the vaccine for clinical trials, securing UK permissions and Malawi regulatory approval.
iiCON is now carrying out the Phase 2a clinical trial in Malawi with approximately 400 participants. The programme will trial ImmBio’s protein-based pneumococcal vaccine on young healthy adults under a controlled human infection model (CHIM) trial delivered through iiCON’s lead partner Liverpool School of Tropical Medicine (LSTM) in Malawi. The sample group will be vaccinated and then inoculated in their nose to understand if they are carrying a strain of the disease or not. This will be compared to the existing PCV13 vaccine and a placebo.
CHIM trials for pneumococcal disease have been well established at LSTM for many years and this trial will build on the current £4.5m MARVELS programme at the Malawi Liverpool Wellcome Programme. MARVELS (Malawi Accelerated Research in Vaccines by Experimental and Laboratory Systems) is a programme to develop CHIM studies in pneumococcus, salmonella and TB, of which the leading project is the now well-established pneumococcal CHIM.
Following the trial, the vaccine could have the potential to be taken forward at scale by an industry partner which could develop and deliver a low-cost vaccine at scale – with potential for manufacturing and distribution across Africa. iiCON and ImmBio are now working to identify commercial partners to support the next stage of development.
The vaccine would be targeted at people at risk of disease and those with a high risk of transmitting infection to others to prevent the transmission of SPN3 in communities in Malawi. The highest transmitting populations in target areas are immunocompromised children and adults, particularly those with HIV. These communities are also exposed to high levels of antibiotics and so prevention of the spread of the SPN3 strain in these people will reduce the emergence of antimicrobial resistance.
Professor Stephen Gordon, director of experimental medicine at iiCON, said: “We’re very pleased to have reached this key milestone in the development of PnuBioVax, which will help to address an urgent health priority and public health issue both in Malawi and worldwide. Not only will it save lives, it will help to upskill and boost the local economy as we very much hope that the vaccine will eventually be manufactured and distributed locally. This way, we can ensure the communities that really need this vaccine will be receiving it. In the development of the vaccine we hope to cover multiple serotypes at low cost and effectively block community transmission.”
Prof Janet Hemingway, iiCON’s founding director, said: “Working to support and accelerate SME innovation is at the heart of iiCON’s purpose and we’re delighted to have reached this key stage in the development of PnuBioVax with our collaborators. Our team has worked closely with ImmBio and our manufacturing partner, Recipharm Advanced Bio, to overcome R&D hurdles and enable a smooth tech transfer process to bring this vaccine forward and into clinical trials at our specialist testing facility in Malawi. We are incredibly excited about the potential this product holds to save lives and play a role in addressing a fast-growing global public health concern.”
Graham Clarke, ImmBio Chairman, said: “The novel platform technology that ImmBio has developed generates a self-adjuvanting multi-component vaccine, needed to elicit a broad response. This Phase 2 trial is designed to generate data supporting prior evidence that response is strain-independent, able to protect against both current and new variants, cost-effectively. Positive data will support progression of other bacterial vaccines currently at pre-clinical stages, where strain variation is also a key challenge.”
Raquel Fortunato, President Genibet, Recipharm Advanced Bio, said: “We are proud to support iiCON and ImmBio in the development of this pioneering pneumococcal vaccine. Our role in advancing PnuBioVax to GMP clinical trial supply demonstrates the strength of true collaboration between industry and academia. By combining our expertise in advanced therapy development and GMP manufacturing with iiCON’s and Immbio world-class translational capabilities, we are helping to accelerate the delivery of affordable, scalable vaccine with the potential to make a real difference to global health.”