This blog was updated on 7 May*

Large numbers of human infectious diseases have a zoonotic origin, meaning that many disease-causing pathogens were originally transmitted from non-human animals to humans. This process can have devastating repercussions for human health, particularly when they reach epidemic or pandemic status. In the last two decades different strains of coronaviruses have caused three major pandemics as they jumped from animals to humans.

In 2002/03 severe acute respiratory syndrome (SARS) caused the first pandemic of the 21st century followed by Middle eastern respiratory syndrome (MERS), which was first identified in 2012. The most far-reaching coronavirus to affect the human population so far is severe acute respiratory syndrome related coronavirus-2 (SARS-CoV-2) which led to the current global pandemic crisis. 

The public health response has been to take a more proactive approach to tackle the most recent pandemic and to improve preparedness for future ones.

Vaccine development is moving from reactive to proactive

Vaccine development is one area where accelerated efforts – and successes – are particularly apparent. During the most recent pandemic, vaccines to reduce severe illness, hospitalisation, and transmission of the virus, were developed at a record rate. Over 13.5 billion doses of vaccines against SARS-CoV-2 have now been administered. 

However, the current vaccine development strategy does not account for the rapid evolution of viruses and their capacity for genetic variation. This evolution can create new variants in a viral genome that facilitate immune escape – where the immune system no longer reacts to defend the body against the virus. 

Vaccines are traditionally developed based on strains already in existence, leaving scientists perpetually trying to catch up with the latest iteration of the virus. Rapidly diminishing effectiveness of the first-generation vaccines – due to the ability of SARS-CoV-2 to continually evolve – make novel, innovative approaches to vaccine design crucial. Despite increasing worldwide immunity to SARS-CoV-2, future variants are likely to be even more transmissible and evasive of immunity. 

Pan-spectrum vaccines are in development

Advances in computational biology are opening new doors for vaccine development and the momentum to develop pan-spectrum vaccines for viral infections has never been greater. 

By utilising the power of genomics and synthetic biology, several pan-spectrum vaccine candidates are undergoing early human clinical trials. 

At the recent Cambridge Infectious Diseases Annual Symposium DIOSynVax (Digitally Immune Optimised Synthetic Vaccines), a spin-out company from the University of Cambridge, showcased their novel approach to future proofing vaccine design. 

The company, headed by Professor Jonathan Heeney, is using a combination of computational biology, protein structure, immune optimisation, and synthetic biology to produce a vaccine effective against a wide range of coronaviruses. The aim is for the vaccine to provide a broad level of coverage, meaning immunity is developed for multiple viruses in the same family or genus and that the vaccine remains effective in the face of ongoing virus evolution. 

How to target multiple variants

One approach could be to target SARS and SARS-CoV-2 and their variants. These viruses are known as sarbecoviruses.

By studying the genetic evolutionary relationships between sarbecoviruses, and using computational modelling, DIOSynVax identifies regions of the genome that code for proteins that must remain constant to enable the survival and reproduction of the virus.

They use this information to develop multiple, synthetic epitopes, which are grafted onto an antigen structure to create a vaccine antigen payload (VAP).  Vaccine antigen payloads are not new. The trick, however, is to develop a vaccine with a payload high enough to provide the necessary breadth and depth of coverage. By targeting those regions of the viral genome that are least likely to change as the virus evolves, the vaccine has the potential to be a one size fits all protection against existing and new sarbecoviruses.

Does it work?

In animal trials, conducted by DIOSynVax, when administering the VAP through multiple vectors, the vaccine was shown to give strong protection against multiple sarbecoviruses, including currently circulating SARS-CoV-2 variants. This, despite the VAP originally being designed prior to the emergence of many of these variants. The VAP also protected against other major coronaviruses including those that caused the original SARS epidemic in 2002. The first human clinical trials are ongoing in Cambridge and Southampton. 

Other companies are also investigating novel approaches to create a pan-sarbecovirus vaccine, with numerous clinical trials underway. OSIVAX, a company currently working on a universal influenza vaccine, have developed a potential pan-sarbecovirus vaccine. Their version targets the invariant viral nucleocapsid – the outer shell that protects the viral genome – to provide a universal breadth of protection. 

The power of genomics, data and synthetic biology

It is difficult to predict the next steps in the evolution of SARS-CoV-2. However, the enhanced transmissibility and sophisticated methods of vaccine-derived immune escape demonstrated by the Omicron variant are a stark warning that traditional vaccine development cannot be relied upon in the future. Development of these ‘future-proof vaccines’ for protection against families of viruses and their potential variants could be the holy grail. By harnessing the power of genomics, data-sharing and synthetic biology, vaccine development has demonstrated a promising new methodology which has the potential to launch a new era of proactive readiness for future viral pandemics. 

*UPDATE

The momentum for developing single vaccines potentially effective against a spectrum of evolving variants is growing. In parallel to DioSynvax, alternative methodologies are coming to the fore.  As reported in Nature, researchers are utilising ‘nanoscale organisation’ to produce ‘nanocages’ – structures containing fragments of multiple sarbecoviruses and designed to elicit an immune response to a broad range of species. At this stage high levels of neutralising antibodies were achieved in mice only; however, this innovative methodology adds another avenue of investigation to pandemic preparedness.