It is well-known that the need to develop vaccines, or rather a vaccine, against future iterations of COVID-19, is pressing. As variants continue to emerge CEPI reports that we are “forever chasing” the virus, meaning we need to change our approach and enter a “new phase of the race”.
Facing the future
Acknowledging the speed and success of first generation COVID-19 vaccines, CEPI is now turning its gaze to the years to come. A report published in September 2022 suggests that the current aim is to develop a “next generation of tools” against SARS-CoV-2 but also future coronavirus threats. This “holy grail” would present pre-emptive protection against variants of COVID-19 but also “novel coronaviruses that have yet to come across the viral frontier”. Thus, the search for a pan-coronavirus vaccine has begun. CEPI’s Dr Melanie Saville describes this as “urgent and challenging work”.*
“The best way to truly be able to end this pandemic and prevent another coronavirus pandemic will be with vaccines that can protect us against future newly emerging coronaviruses and against new variants of this one.”
Full steam ahead
CEPI identifies the task of producing a variant-proof or pan-coronavirus vaccine as “high-risk, high-reward”. It is deeply complex and would require a “future-changing scientific and medical breakthrough”. On the other side of that, then, would be the guarantee that the world will “never again be hit by a pandemic caused by a coronavirus”.
CEPI “recognised the wider coronavirus threat early”, it says. This prompted a call for proposals in early 2021. So far it has awarded almost $200 million in grants across 11 partners. This broad approach offers a greater chance of success. CEPI proudly states that it is “by far the leading funder of research and development” in this race. Following this is the US NIH, which has contributed $36 million.
Many of the groups that are focusing on coronaviruses are pushing against the most worrying so far: the betacoronavirus group. This includes the original SARS-CoV-1, MERS-CoV, and the more recent SARS-CoV-2.
A new focus
CEPI suggests that the “core” of the problem is immunogen design. Specifically, shifting the focus from the “prominent bits of the coronavirus’ infamous ‘spike’ protein” to more “stable” areas. These would be less likely to mutate, enabling greater protection from just one vaccine. Dr Saville believes that “we need to look for conserved epitopes”. However, these are usually hidden, so “a lot of the work” that is currently happening is attempting to “expose them”.
Dr Christopher da Costa echoes the need to have “common structural elements” that are “conserved across different sub-groups”. Thus, as the exposed parts of the ‘spike’ mutate, a vaccine would still be effective.
“We want to have several shots on goal, so we’ve made sure we have a nice mix of technologies and antigen designs.”
CEPI states that scientists are currently “exploring a whole kaleidoscope of different vaccine technologies”. These include mRNA-based projects and mosaic nanoparticle-based vaccine candidates. Further research uses artificial intelligence.
Projects in motion
Some of the highlights shared by CEPI include:
- CalTech’s project to develop a novel protein nanoparticle vaccine. This is reportedly showing promise in animal studies. Known as a “Mosaic-8” vaccine, it uses protein nanoparticles containing a “type of protein ‘glue’ that attaches to antigenic sections of the spike proteins” from 8 coronaviruses. This will hopefully “train the immune system” to produce antibodies that are directed against conserved places on viral fragments.
- An extended partnership with SK Bioscience in South Korea to develop a variant-proof vaccine candidate. This is a recombinant-protein vaccine based on a “two-component self-assembling nanoparticle platform” that was developed at the University of Washington. The intention is that this vaccine, which presents the immune system with receptor-binding domains from multiple sarvecoviruses, will “prime the immune system” to identify and target a variety of viruses and variants.
- A project led by DIOSynVax, from the University of Cambridge. This is an mRNA candidate that targets common elements of viral structures. These are “critical” to the virus’ survival and replication, so are less likely to change or mutate when variants emerge. It is hoped that when the immune system encounters these antigens it will produce neutralising antibodies and T-cells against a range of betacoronaviruses.
- A consortium led by BioNet. The French-Thai manufacturer is working on a potential vaccine using multiple mRNA molecules. These encode for several target immunogens from several variants. They aim to produce an effective COVID-19 vaccine that is also used as a “model for how to make similar mRNA-based vaccines”.
- The University of Saskatchewan’s Vaccine and Infectious Disease Organisation’s (VIDO) multivalent-type approach. This takes elements from several variants and combines them with an adjuvant.
Easy access in mind
So far, positive data are emerging. The next step, says CEPI’s Emma Wheatley, is access. She states that this is at the “heart” of CEPI’s process.
“We have to be sure we’re working towards something that will be able to be made, delivered, and administered in all countries for all people”.
For many of these projects, access is certainly central to development. For example. Studies have revealed that nanoparticles like those used in the Mosaic-8 candidate can be freeze dried into powder form. This can be distributed widely and then rehydrated for injection. Other options include needle-free injection, which involves a “short high-pressure burst of air that pushes the vaccine into the skin”.
Progress is steady, and CEPI reports that several partners are hoping to start Phase I trials in mid-2023. Dr Saville says this would be “complex, but also scientifically feasible”.
“The level of technology and innovation we’ll need to use in these broadly protective coronavirus vaccine approaches is really taking things up a notch”.
*To hear from Dr Saville at the World Vaccine Congress in Europe 2022 click here to get your tickets.
