The Omicron Variant Highlights the Need for Smarter, Future-Proof Vaccine Design

The rapid rollout of COVID-19 vaccines in many parts of the world is the greatest success story of the pandemic, preventing serious illness, deaths and long-term side effects from the virus and setting the course for economic recovery. But the emergence of the new highly mutated Omicron variant has raised fears that the current crop of vaccines may no longer be sufficiently effective.

The virus behind COVID-19, SARS-CoV-2, is closely related to other, more lethal coronaviruses such as SARS-CoV-1 and Middle Eastern Respiratory Syndrome (MERS). We have been relatively lucky that it was the less dangerous – albeit more contagious – member of this family that caused the pandemic. The events that enabled these viruses to start infecting and spreading among humans continue to happen all the time, and it’s only a matter of time until it happens again.

While there is still a long road ahead to control the COVID-19 pandemic – and the world waits anxiously for answers about the potential impact of Omicron – one thing is for certain:  we need to do more to stay ahead of infectious diseases; whether that’s variant forms of the pathogens we see now, or the next pandemic.

Antigen design is the key to more effective vaccines

Investment in vaccine science and technology development can provide us with the tools to respond to pathogens with pandemic potential.

In recent years, vaccine research has largely centered on the development of better and safer delivery systems, such as viral vectors, DNA and mRNA-based vaccines, as well as more effective immune-stimulating adjuvants. However, far less attention has been paid to the component at the heart of every vaccine: the antigen. An effective vaccine relies on effectively presenting information about a pathogen to the immune system, training it to respond should we encounter the pathogen for real. Even if a vaccine has a highly effective delivery system and adjuvant, it is worthless if the body's immune cells and antibodies cannot recognize the pathogen that circulates and causes disease.

Furthermore, if the pathogen evolves, and there are changes in the protein that has been selected as a vaccine antigen, then it may be able to evade vaccine-mediated protection. We see this in the case of influenza, which mutates rapidly and requires new vaccines to be designed every year. There are also many other pathogens for which we simply have not found suitable antigen, and therefore have no vaccine.

Drawing again on the example of COVID-19, the currently available vaccines are all based on the Spike protein that decorates the surface of the virus. This is an ideal antigen, as antibodies can neutralize the virus before it enters the cells. Focusing on the Spike alone meant that vaccine developers were able to rapidly create a highly effective vaccine that could be rolled out worldwide in less than a year. However, significant mutations in the Spike could render these vaccines less potent, or even useless.   

Creating universal vaccines

The solution is to develop universal, future-proof vaccines with a broader profile of protection, meaning that they can protect not only against the variants that exist now, but also those that are likely to emerge, as well as closely related pathogens.

The major bottleneck to achieving this is the identification of an antigen that captures current and emerging pathogens. This is not a simple task, but novel technologies including advances in genomics, proteomics and data science now offer unprecedented insights into how to design antigens for universal, future-proof vaccines.

A number of researchers in academia, start-ups, and biotech are tackling this issue, making use of big-data and machine learning to understand pathogen evolution and how to best represent diversity in vaccine antigens.

One approach developed by theoretical biologist Bette Korber looks for key variable regions in different strains or species, using this information to create a mosaic antigen protein. This is currently being tested against HIV, one of the biggest challenges for vaccine developers. Other ideas rely on identifying regions that are conserved and shared amongst different strains or even species.

Sifting through all this biological data in search of insights about the most appropriate antigens is a task well suited to artificial intelligence (AI). AI algorithms can analyze large and varied genomic, evolutionary, clinical and epidemiological datasets to find critical pieces of proteins in pathogens that either highly variable or highly conserved.

This information can then be used to create entirely artificial “pick and mix” antigens formed by a string of epitopes (the units within a protein recognized by antibodies), providing the immune system with everything it needs to know to mount an effective response, both now and in the future. AI-informed design has the potential to create universal, future-proof vaccines that will be effective across a family of closely related pathogens. This concept has already underpinned the development of a novel vaccine for the mosquito-borne tropical disease chikungunya, and a therapeutic vaccine for treating Human Papillomavirus (HPV) that causes cervical and other cancers. Both of these vaccines are in clinical trials, and others for human and animal diseases – including COVID-19, malaria and African Swine Fever – are also in development.

We may always be locked in an evolutionary arms race with infectious diseases, but we have science on our side. Using smarter antigen design to develop universal, future-proof vaccines will enable us to get one step ahead, helping to protect the world against emerging threats and reducing the chances of another pandemic on this scale ever happening again.