Animal studies on a ‘future-proof’ vaccine technology have revealed that only one antigen may be tweaked to create a broadly protective immune response. According to the findings, a single vaccination containing a combination of these antigens (a material that induces the immune system to develop antibodies against it) could protect against a broader spectrum of existing and future coronaviruses.
In early 2020, the vaccine technology developed by the University of Cambridge and spin-off DIOSynVax provided protection against all known variants of SARS-CoV-2, the virus that causes COVID-19, as well as other major coronaviruses, including those that caused the first SARS epidemic in 2002.
The studies in mice, rabbits, and guinea pigs – an important step before starting human clinical trials in Southampton and Cambridge – discovered that the vaccine candidate provided a strong immune response against a variety of coronaviruses by targeting the parts of the virus required for replication. The vaccine candidate is based on a single antigen that has been digitally created and immune-optimized.
Despite the fact that the vaccine was developed prior to the emergence of the Alpha, Beta, Gamma, Delta, and Omicron variants of SARS-CoV-2, it provided strong protection against all of these variants as well as more recent variants, implying that vaccines based on DIOSynVax antigens may also protect against future SARS-CoV-2 variants.
DIOSynVax (Digitally Immune Optimised Synthetic Vaccines) combines computational biology, protein structure, immune optimization, and synthetic biology to maximize and broaden the spectrum of protection that vaccines can provide against global threats such as current and future virus outbreaks. Its vaccine candidates are adaptable to a wide range of vaccine delivery and manufacturing platforms. The findings were published in the journal Nature Biomedical Engineering.
Since the SARS outbreak in 2002, coronavirus ‘spillovers’ from animals to humans have been a threat to public health, and require vaccines that provide broad-based protection. “In nature, there are lots of these viruses just waiting for an accident to happen,” said Professor Jonathan Heeney from Cambridge’s Department of Veterinary Medicine, who led the research. “We wanted to come up with a vaccine that wouldn’t only protect against SARS-CoV-2, but all its relatives.”
All currently available vaccines, such as the seasonal flu vaccine and existing Covid-19 vaccines, are based on virus strains or variants that arose at some point in the past. “However, viruses are mutating and changing all the time,” said Heeney. “Current vaccines are based on a specific isolate or variant that occurred in the past, it’s possible that a new variant will have arisen by the time we get to the point that the vaccine is manufactured, tested and can be used by people.”
Heeney’s team has been working on a new approach to coronavirus vaccinations by focusing on their “Achilles heel.” Instead of only targeting the virus’s spike proteins, which alter to avoid our immune system, the Cambridge vaccine targets the virus’s essential sections, which are required to complete the virus’s life cycle. These areas are identified via computer simulations and the selection of conserved structurally designed antigens. “This approach allows us to have a vaccine with a broad effect that viruses will have trouble getting around,” Heeney stated.
Using this method, the researchers discovered a novel antigen structure that elicited broad-based immune responses against many Sarbeco coronaviruses, a wide collection of SARS and SARS-CoV-2 related viruses found in nature. The optimized antigen was administered as a DNA immunogen (in collaboration with the University of Regensburg), a weakened version of a virus (Modified Vaccinia Ankara, supported by ProBiogen), and an mRNA vaccine (in collaboration with Ethris). In all cases, the optimized antigen elicited a significant immune response against a variety of coronaviruses in mice, rabbits, and guinea pigs. The “first-in-human” clinical trials are under underway at the NIHR Clinical Research Facilities in Southampton and Cambridge, based on a strong safety profile. The final booster immunizations will be administered by the end of September.
“Unlike current vaccines that use wild-type viruses or parts of viruses that have caused trouble in the past, this technology combines lessons learned from nature’s mistakes and aims to protect us from the future,” said Heeney. “These optimised synthetic antigens generate broad immune responses, targeted to the key sites of the virus that can’t change easily. It opens the door for vaccines against viruses that we don’t yet know about. This is an exceptionally different vaccine technology – it’s a real turning point.”
The study was first supported by the DHSC UK Vaccine Network initiative, and was later supplemented in part by the Innovate UK DIOS-CoVax program. The DIOSynVax pipeline include vaccine candidates for influenza viruses, hemorrhagic fever viruses, and coronaviruses such as SARS-CoV-2, which is currently in clinical testing.
DIOSynVax is a University of Cambridge spin-out firm founded in 2017 with the assistance of Cambridge Enterprise, the University’s commercialization arm. Jonathan Heeney is a Fellow of Darwin College and a Professor of Comparative Pathology at the University of Cambridge.
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