As California emerges from Omicron, other places are back in the block or facing record caseloads after trying and not avoiding the variant. Many of us who did everything right, get all shots and boosters and avoid humans, are still infected.
COVID’s persistence could push us to a concession on just love I have a virus. But that seems defeatist, and is dangerous. Highly contagious variants have erupted from parts of the world that still have low vaccination rates and high population densities. New research finds accelerated cognitive decline and cardiovascular problems after even mild COVID infections. Over a dozen animal species are now known to be infected with SARS-CoV-2, setting the stage for new mutations. We now need a new approach to defeat future waves of this virus and other viruses that may arise.
This indicates a lifelong, durable, broad-spectrum vaccination. What will it take to develop one? There is a difficult road, but it is possible. Success will require two principles that the world has not yet sufficiently embraced in the fight against this virus: a focus on long-term and short-term, and a sustainable structure and support for cooperation.
One challenge is that there are so many viral sequences against which the vaccine must protect, arising not only from emerging SARS-CoV-2 variants, but also from the multitude of other coronaviruses that can still play into humans. The first generation mRNA vaccines, which teach the body to recognize the spike protein part of the virus and build up an immune response, encode a viral strain that is no longer circulating. Because this protein is so susceptible to mutation, which makes it harder for the body to recognize in future variants, a more universal vaccine must target parts of the virus that are shared between different viruses in the family – often essential components that are less likely to mutate .
Unfortunately, these parts are often less conspicuous by the immune system. Science has since found better ways to require a more effective immune response to the spike protein, and better ways to construct and demonstrate the protein itself, but finding the right combination of different strategies will take coordination.
And we are not sure whether the mRNA format, which emerged as a vaccine strategy after decades of development, is best against the next new pathogen, compared to other vaccine approaches such as the use of nanoparticles that allow more possibilities for vaccine formulations or killed. Viruses, or viral vectors, that contain a wider variety of molecules and can trigger protective viral sensing mechanisms.
To handle these complexities, we need all sorts of experts – including developing new vaccine formats to achieve an effective, long-lasting immune response and to understand the vaccine components that cause immune cells to act. We need experts who understand how antibodies not only inactivate the virus but also recruit an army of complementary immune cells to remove the pathogen from the body. We also need experts and preclinical models to help us understand how vaccine candidates progress in human studies, and how they assess their success. And we need experts in large-scale vaccine production, cost and distribution logistics.
Each of these hurdles is addressed by different groups of scientists, all working in a different discipline and in a separate place. The right vaccinations will probably not be done by a group or a company alone, but will come from a consistent effort of many approaches that overcome various variables. So worldwide, researchers need to collaborate on the scale and style of the Manhattan Project to build a lasting solution. Because researchers have already come up with better solutions than the early 2020 approach, they have a lot to start with. Many labs are already pursuing different paths to universal vaccination.
The scientific enterprise, however, is built on competition, not on mass collaboration without respect for your individual career. Competition has advantages: It encourages innovation, drives us to get results faster and delivers a better result or product than that of our competitors. The downside is the lack of sharing – of results, samples and crucial insights. Competition for limited funding and the need to publish first results can lead to siloing and a focus on quick results instead of thorough ones.
It is easy to call for sharing and coordination, but that call is ignored without structures to support and encourage researchers. Both of us know this firsthand: We were involved in building large, multidisciplinary collaborative efforts between competitors to discover research problems no single lab could try on its own. This requires systems to be created and revised to simultaneously develop and evaluate competitive ideas or treatments, supported by data-driven machine learning approaches that evaluate results on a level playing field. These approaches made it possible to understand why some antibodies were protective and others not, and how laboratory experiments identified the treatments that were most successful in humans.
Our collaborative approach has worked because they have set up individual labs to be successful, while also contributing to greater good. Participation lab researchers had to publish papers coming out of the projects so that their time and effort would contribute to continuing their careers rather than costing them. They also need protection of their intellectual property so that they are able to participate and share, in addition to funding to support work on a larger scale or depth than their current funding sources allow.
Companies that have given access to their researchers and supplies meanwhile need a concrete advantage: they get valuable data that they can use for new drug registrations, and the work of the consortium would open new doors for their products. The federal and philanthropic funders of these projects also received a strong bang for their buck: a body of knowledge that bridged barriers and advanced the field as a whole.
Motivating philanthropic and federal funders will be essential to develop longer-lasting, broad-spectrum vaccines. Since vaccines usually do not make much money – a good lifelong vaccine could be administered once, and for many in the world it must be donated – federal governments and large philanthropic organizations have to account for the bulk of the investment.
They may not feel motivated to continue now: While in the past during the pandemic the US government and other financiers were driven by a sense of immediate crisis, now the focus is on widespread recovery. They may be less willing to avoid what now feels like a potential crisis. Funding and interest in developing vaccines for 2003’s SARS-CoV-1 dissolved after the virus left; by 2020, we can use that knowledge and drugs that would have arisen.
In addition to the further health risks of COVID, the economic argument for more vaccine investment is difficult to dispute. The cost of the SARS-CoV-2 pandemic is estimated at $ 16 trillion, or nearly 90% of US GDP. The cost of developing a typical vaccine, more than $ 1 billion, is 0.006% of that. Even a $ 10 billion vaccination is minuscule compared to the pandemic toll. We can not afford not to do better.
Erica Ollmann Saphire is President, CEO and Professor at the La Jolla Institute of Immunology. Edward Scolnick is a core emeritus at the Broad Institute of MIT at Harvard and former head of R&D at Merck Research Laboratories.
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