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Reviews |  The vaccines we have are good.  But they could be so much better.

Shortly after the emergence of the new coronavirus, its genome was sequenced and vaccines were being developed at, yes, warp speed. These are all Herculean tasks that deserve praise. But America’s feat ends there. The initial vaccination strategy was reactive and tactical, not decisive and strategic. Although he prioritized getting safe and effective vaccines into the body as quickly as possible, he did not consider how to prevent variants or subsequent waves of the virus.

All coronaviruses produce variants, and as with previous coronavirus outbreaks, variants of SARS-CoV-2 emerged as the virus spread from Wuhan, China, across the planet. The next danger is the continued evolution of variants that can overcome the immunity provided by existing Covid-19 vaccines and past infections.

The second generation of Covid-19 vaccines, which are currently in development as a booster, target known variants, but they are not designed with future variants in mind. This is the development of a “whack-a-mole” vaccine, an ineffective and costly approach that drives out yesterday’s virus. What we need is a ‘kill shot’ immunity, which would protect people from all current and future variants and end the pandemic.

It is possible to make a vaccine like this – if scientists closely study the mutation patterns of viruses and design vaccines for the viruses we are about to face, not just the ones we have now. This approach is especially important given the number of ways viruses can emerge in humans, including from a natural spillover (when a virus spreads from one species to another) or from an accident. in a virus research lab (“lab leak”) – two scenarios that are, rightly, the subject of serious investigation.

Whatever the results of these investigations, the United States must use this pandemic to ensure that emergency vaccine development can meet all possibilities.

Conversation of opinion
Questions around the Covid-19 vaccine and its deployment.

One approach is to predict which variants are most likely to occur in a circulating virus and prepare to defeat them in advance using pre-designed vaccines. It might sound futuristic, but the ability already exists.

The ability to predict and counter naturally emerging pathogens, as well as genetically modified ones released by unregulated labs, was first developed by the US government over a decade ago. In 2008, while working at the Defense Advanced Research Projects Agency, also known as Darpa, our team, led by Dr Callahan, became alarmed at a series of bird flu outbreaks in the country. man associated with several foreign poultry vaccine companies.

We were particularly concerned that well-intentioned but unregulated viral research in foreign laboratories could produce viruses that are highly infectious and capable of rapidly spreading in human populations. Between 2008 and 2016, Darpa developed a program called Prophecy to study the evolution of viruses in order to predict mutations and develop vaccines. The agency combined it with an alert network run by doctors working in at least seven hospitals around the world, including places like Singapore; Jakarta, Indonesia; and Hong Kong.

Here’s how Prophecy worked: First, researchers studied the genome of a dangerous virus to identify areas where the virus can mutate without destroying its ability to reproduce. The overwhelming majority of mutations weaken a virus, so most mutations can be ignored. Second, the scientists used computer models to test for the remaining mutated viruses and simulate any possible changes in surface proteins, which are important for a virus’s ability to infect. Scientists then designed antibodies on a computer to target these proteins and help the body recognize and fight the virus. By working with our research partners, we were able to confirm our predictions by sequencing the most recent variants obtained from patients around the world. Scientists can further tune the vaccine or design antibody based on the immunity seen in people who survived the infection.

In addition to boosting global health and safety, technologies and processes developed under Prophecy have helped pharmaceutical companies make experimental vaccines and antibodies more quickly to treat cancers that have eluded the immune system. the patient, and medications that would prevent the emergence of antibiotic-resistant microbes. .

Unfortunately, changes in political leadership in the United States in 2016 along with budget changes resulted in the demise of research collaborations in nine countries, including China, Russia, Indonesia, and Nigeria.

The Biden administration’s re-engagement in global health signals an opportunity to restart Prophecy or a similar program.

As the United States enters the 18th month of the pandemic, the country should carefully reconsider the next steps in vaccine development. We must re-establish research collaborations overseas and re-establish surveillance in international hot spots where animal-to-human infections commonly occur, in China and other countries. Second, the United States must resume relationships with foreign laboratories that work with dangerous pathogens to ensure safe, secure, and ethical best practices. These collaborations can be encouraged by sharing technologies such as mRNA vaccines. Third, Prophecy and similar tools need to be updated to better assess whether a virus is natural or modified. Determining the origin of a virus allows officials to put in place controls to reduce the frequency and severity of future pandemics.

While the first act of Prophecy was an accurate prediction of pathogen evolution, it is the second act of the program that serves us best now: the ability to anticipate viral mutations before they occur and to counter mutations with vaccines. These types of vaccines are already being studied in advanced clinical trials to prevent the recurrence of drug-resistant cancers and to produce a universal influenza vaccine. Bringing these technologies to the fight against coronavirus variants could help end the current pandemic and prevent the next. The nation should act quickly.

Michael V. Callahan is a former Covid-19 Special Advisor to the Assistant Secretary for Public Health Preparedness at the Department of Health and Human Services, and has served as Incident Commander for nine international outbreaks of very dangerous pathogens . He is Director of Clinical Translation at the Vaccine and Immunotherapy Center at Massachusetts General Hospital. Mark C. Poznansky is an infectious disease physician and director of the Vaccine and Immunotherapy Center at Massachusetts General Hospital and Associate Professor at Harvard Medical School.

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