Dr Frederik Kristensen on COVAX: ‘The biggest mass immunisation effort in history’.
CEPI is an international foundation that takes donations to finance independent research projects in vaccine development. How many COVID-19 vaccine candidates does CEPI currently have in its portfolio?
Frederik Kristensen: As vaccine development is risky and complicated, CEPI chose to invest in a portfolio of diverse vaccines using both traditional and innovative technologies. We have built the world’s largest portfolio of COVID-19 vaccines: 12 vaccine candidates of which 10 are in active development. This includes Moderna and University of Oxford/ AstraZeneca which have received WHO Emergency Use Licensure (EUL) status and are approved in several countries around the world following positive assessment by national independent regulatory authorities and regional bodies. Most recently, another COVID-19 vaccine candidate, developed by Novavax and supported by CEPI, has also published extremely positive Phase III trial data.
Why do you have such a large portfolio, and do you expect to add more to it?
Frederik Kristensen: A large portfolio increases our chances of developing many successful vaccines and meeting our goal of advancing three to licensing. This diversity is crucial if we are to meet global demand and protect vulnerable populations.
We select vaccine candidates either through our funding of the CEPI partners already there at the start of the outbreak, or through reviewing calls for proposals. Our investment decisions are based on three key criteria – speed, scale, and access. And we are now expanding our portfolio by investing in ‘next-generation’ vaccine candidates.
These candidates could for example include single-dose shots, more robust and stable vaccines that do not require complex cold chains. And they also might include innovative delivery methods such as nasal sprays. We are also supporting partnerships to ‘future-proof’ vaccines against mutating strains.
How will CEPI independently evaluate the vaccine candidates and recommend the most effective ones?
Frederik Kristensen: All the vaccine candidates we invest in were identified as promising by in-house and external expert reviewers. The progress of these candidates is actively assessed on a regular basis as data comes in.
Ultimately, however, decisions on whether to authorise a vaccine, or to make it available for emergency use, lie with the stringent and independent national regulatory authorities. Their reviews are based on data from clinical trials supported with CEPI investments. But, while we are not directly involved in this, we have created a system to reliably assess immunological responses generated by our vaccine candidates and others in development.
We have a network of nine laboratories all over the world spanning Europe, Asia, North America and Latin America. They all follow the same standardised protocols and use the same tests to evaluate samples from participating vaccine developers. This removes much of the variability and allow for head-to-head comparisons of the immune responses induced by multiple vaccine candidates.
How does CEPI use its funds and knowledge to contribute to vaccine development?
Frederik Kristensen: CEPI directly funds the development from preclinical and clinical testing. As mentioned, we are supporting vaccines based on three key principles:
- speed (there is no time to lose – we need vaccines that can be developed rapidly);
- scale (we’ll need billions of doses to end the pandemic, so we have to be able to manufacture vaccines in huge quantities), and;
- universal access (the fastest way to end the pandemic is to protect those most at risk, wherever they are in the world).
We are also supporting broader efforts that can provide data, networks, and structures in order to quickly, and successfully, tackle infectious disease outbreaks. For example, CEPI is funding the development of COVID-19 international antibody standards for assessing immune responses induced by vaccine candidates undergoing testing. We have also set up a scientific taskforce to track and test the impact of novel variants.
As co-leaders of COVAX (alongside our partners Gavi and WHO, and our key delivery partner UNICEF) we aim to enable equitable access to COVID-19 vaccines worldwide, regardless of location or income. So, in line with these goals, we have also made strategic investments in vaccine manufacturing to minimise bottlenecks and produce doses ahead of time.
This includes reserving manufacturing capacity at a network of facilities and securing glass vials to hold two billion doses.
Have you been involved with a vaccination programme of this magnitude before?
Frederik Kristensen: This broad global effort to deliver safe and effective COVID-19 vaccines globally will be the biggest mass immunisation effort in history. Since the first vaccines arrived in Ghana in February, as of 17 June 2021, COVAX has delivered more than 88 million doses to 131 economies.
This is a pivotal point in our work to close the vaccine equity gap and save lives globally. However, considering the needed size of this effort, inequity in vaccine distribution remains globally. The devastating situation in India, alongside manufacturing bottlenecks and the emergence of new variants has meant that COVAX hasn’t been able to deliver at the speed and scale originally forecast.
Nonetheless, with greater funding, freeing up supply chains and significant dose donations – as was announced by G7 leaders last week – the original objective of delivery of 2 billion doses of vaccines worldwide in 2021, and 1.8 billion doses to 92 lower income economies by early 2022 is still within reach.
What did you do before COVID-19 broke out?
Frederik Kristensen: Before the SARS-CoV-2 virus emerged, CEPI was working on vaccines for other emerging infectious diseases with epidemic potential. This list includes the related coronavirus that causes Middle East Respiratory Syndrome (MERS), the Lassa fever virus, Nipah virus, Rift Valley fever virus and Chikungunya virus. We have also supported clinical trials for the secure licensure for Ebola vaccines.
CEPI has also invested in platform technologies that can be used for rapid vaccine development against unknown pathogens.
What are the unique challenges of the COVAX programme?
Frederik Kristensen: This programme was created as a means to pool demand and achieve equitable distribution and thus improve chances of controlling the pandemic everywhere. The idea was also to avoid the scenario observed during the 2009 H1N1 bird flu pandemic, when rich nations bought up vast amounts of the globally limited supply of vaccines.
What is unique is that is offers an entirely new system for tackling global disease outbreaks. The world has never before had an end-to-end system for developing, manufacturing and deploying vaccines globally in order to ensure equitable access for all vulnerable populations.
So we had to, whilst implementing the programme, advancing and delivering vaccines, build this new system from scratch and get it financed. This has been referred to as ‘flying the plane while building it’. It is challenging, but it means that we can be flexible and adapt to a developing situation.
We are having to work through issues of reduced supply as manufacturers scale and optimise their production processes, as well as increased demand for COVID-19 vaccines in India as the epidemic surges there.
However, we have still achieved an incredible amount, with several safe and effective vaccines in use across the world under emergency authorisation.
But we must recognise that the job is not yet done. We need to secure more doses and more funding, and continue the search for even better vaccines. Other complexities lie ahead, including regulatory approvals, country readiness and capacity, fluctuations in supply, delivery, and logistics. These are all urgent challenges that are being addressed by COVAX partners. We and our partners must continue to work together if we are to successfully deliver the largest and most rapid global vaccine rollout in history.
What has CEPI learnt in the response to COVID-19 that may be useful in future pandemics?
Frederik Kristensen: We’ve all learnt so much since the virus emerged in January 2020: it is estimated that 10 years of vaccine R&D has been completed in less than 12 months. This has provided us with a wealth of data and experience to tackle tomorrow’s big outbreaks.
Furthermore, this pandemic has guided much of our thinking in preparing for future crises. In March 2021, we launched an ambitious five-year, €2.9bn plan to dramatically reduce the future risk of pandemics and epidemics, potentially averting millions of deaths and trillions of euros in economic damage next time.
We also aim to compress the vaccine development timeline even further to 100 days: a third of the time that it took to develop a successful COVID-19 vaccine. We are pleased to see that the G7 have embraced this goal so that we can more quickly and effectively respond to future outbreaks. And we have launched a funding call to work on broadly protective vaccines against beta-coronaviruses (the genus that includes SARS-CoV-2), which would protect against novel COVID-19 variants as well as related coronaviruses that are yet to emerge.
With this, we are working to build a world that is better equipped to deal with these devastating diseases.