Variant-proofing vaccines: Novel candidates seek to offer broad protection
The emergence of Omicron at the end of last year came as a reminder that COVID-19 variants will continue to emerge periodically, with some having the potential to cause new waves for pandemic globally and evolve away from the strains targeted by current vaccines.
In readiness for such an event, CEPI is supporting companies developing broadly protective SARS-CoV-2 vaccines, alongside a more ambitious goal for broadly protective betacoronavirus vaccines, with a pot of up to $200m for promising vaccine candidates.
COVID-19 vaccines and beyond
One goal is to provide greater protection against COVID-19 variants.
“We do not want to live in a world in which we must develop and administer new boosters every time a new, dangerous COVID variant emerges,” said Dr Richard Hatchett, CEO of CEPI, speaking just before Christmas as he reflected on the past year and the emergence of Omicron.
"If you accept that hypothesis, then you should agree that we need better, more broadly protective, more durable COVID vaccines. And if we want them, we will need, collectively, to invest in the research and development to produce them. This should be a matter of the greatest urgency, and something we pursue even as we do everything we can to deploy the vaccines that we have to greatest effect."
But the ambitions are much wider than this. CEPI wants to develop vaccines that generate protection against a broader range of betacoronaviruses.
Including but not limited to SARS-CoV-2, betacoronaviruses are types of coronavirus that cause Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS), which have been responsible for major epidemics in Asia and the Middle East in recent years.
The emergence of a coronavirus combining the transmissibility of COVID-19 with the lethality of SARS or MERS could be devastating to civilization, notes the CEPI, saying that finding solutions to mitigate this threat is thus an issue of the greatest global urgency.
It wants to build on the technological advances that have been made in response to COVID-19 to develop all-encompassing vaccines that could work against known betacoronaviruses, including SARS, MERS, and COVID-19, and could potentially be used to quickly supress future outbreaks of other novel coronaviruses that might jump into the human population.
The holy grail is to create vaccines with the potential to protect against future unknown pathogens, referred to as Disease X.
Vaccine development in action
At the moment, CEPI’s main focus is to support the research and development of novel immunogens - antigens that elicit an adaptive immune response - for use in vaccines that can elicit durable, broadly protective immune responses. It has recently announced grants for two vaccine candidates.
It is supporting South Korea’s SK bioscience with up to $50m to develop a variant-proof candidate against sarbecoviruses: the subgroup of betacoronaviruses containing SARS-CoV (SARS) and SARS-CoV-2 (COVID-19).
The funding will support immunogen design, preclinical studies and Phase 1/2 trials.
The vaccine candidate is a recombinant-protein based on a two-component self-assembling nanoparticle platform developed at the Institute for Protein Design (IPD) at the University of Washington (as is SK’s vaccine candidate against COVID-19, GBP510, which is currently in Phase 3 trials).
It displays receptor-binding domains (RBDs) of multiple sarbecoviruses (the RBD being the portion of the spike protein that enables the virus to bind to and infect human cells)
Potential advantages of this vaccine candidate include broad protection against SARS-CoV, SARS-CoV-2 variants and additional novel sarbecoviruses; scalability; and thermostability.
And the nanoparticle platform could also be fitting to develop vaccines against Disease X.
Another candidate being backed by CEPI comes from the US’ Affinivax, a Cambridge, Massachusetts-headquartered company which was founded in 2014 with a seed investment from the Bill & Melinda Gates Foundation.
The company is receiving up to $4.5m to support initial development of a vaccine candidate based on its Multiple Antigen Presenting System (MAPS) technology platform. The platform allows for multiple polysaccharide and protein antigens to be effectively incorporated in a single vaccine, achieving the potential for 'unprecedented levels of immune response and disease protection', according to the company.
CEPI’s investment in Affinivax will fund vaccine candidate design and selection, manufacturing process development and preclinical testing against specific SARS-CoV-2 variants; establishing a proof of concept for a COVID-19 vaccine that can protect against new variants and is suitable for use in low and middle income countries.
The tech platform may potentially be applicable for developing vaccines which are protective against a broad range of betacoronaviruses, as well as other pathogens in the CEPI portfolio, including ‘Disease X’.
The MAPS technology platform has already been clinically validated with Affinivax’s lead 24-valent pneumococcal vaccine candidate, which was observed to be safe and well tolerated and generated an antibody response to each of the 24 pneumococcal polysaccharides and to the two conserved pneumococcal proteins in a Phase 2 clinical trial.
“Our MAPS technology platform represents a fundamentally different approach to vaccine development that allows us to combine multiple antigens into a single MAPS vaccine to potentially address the continued threat of emerging COVID-19 variants,” explained Stephen Brugger, CEO of Affinivax.
“Additionally, this grant will allow Affinivax the opportunity to explore the potential of our vaccine platform against other viruses and continue to support global health organizations in their efforts to target other viral pathogens and diversify their vaccination programs.”
