The description of the dream product for protection against pandemics sounds deceptively simple: you start off with a sample from a person infected with an unknown pathogen and use it to develop effective new ways to prevent or treat the disease. Speed is the key to success. It has been calculated that, if a strain of the influenza virus emerged today as contagious and deadly as the one that caused the 1918 pandemic, it would claim the lives of 250 million people [10]. By October 2021, Covid-19 had so far caused over 4.7 million deaths worldwide and put health systems and economies under extreme pressure [11].
This much-needed pandemic protector – thanks to Sabeti’s and Crowe's results – is now no longer merely a visionary idea, but instead a realistic possibility. Sabeti, who, together with her team, contributed to containing the Ebola outbreak in West Africa, is focusing on reading the nucleic acid sequences of disease pathogens as quickly as possible to uncover its secrets. The development of new diagnostic methods is a vital step in containing an outbreak - leading to tests that can quickly and accurately identify people who are infected with a viral pathogen - and track its spread and evolution. “New methods like CRISPR-Cas13, which is best known as a gene-editing tool are extremely helpful for this,” explains Sabeti. “This enables the development of a specific diagnosis methodology for viral diseases, while also making it easier to identify mutations arising in the viral genome. The method could even be used for the total destruction of an RNA virus - leading to new antiviral therapies.”
Sabeti and her team have been at the forefront of employing these cutting-edge methods to develop and scale genomic surveillance, diagnostics, and advanced analytics to improve our pandemic preparedness. They have also built a close partnership with the African Center of Excellence for Genomics of Infectious Diseases (ACEGID), which provides state-of-the-art infrastructure and research capacity for Nigeria and the wider continent.
With the outbreak of Covid-19, Sabeti’s team accelerated their work on developing systems to rapidly sequence viral genomes and characterize important mutations early in the outbreak. They characterized the important role of superspreading events in propelling the pandemic. In tandem, her ACEGID partners sequenced the first SARS-CoV-2 genomes from Africa and became a continental World Health Organization (WHO) reference center. The team has also been interrogating genomic data to understand what parts of the virus are presented to the immune system during infection, and how this might influence vaccine development.
In 2020, Sabeti and her team also continued their work into developing new capabilities for the detection of viral pathogens. They developed two groundbreaking diagnostic technologies: CARMEN, a CRISPR-based method for multiplexed viral detection in a laboratory setting and a complementary, field-deployable, point-of-care platform for SARS-CoV-2 detection called SHINE. These two techniques bridge urgent gaps in existing diagnostic capabilities, such as cost, sensitivity, and turnaround time.
The Sabeti team is now using machine learning models to further improve and refine their viral diagnostics. Ultimately, Sabeti sees these as vital tools that will help identify and contain new viral outbreaks early, with the goal of detecting high-priority viruses within an hour, any known human virus within a day, and previously unknown viruses within a week.
Importantly, Crowe’s research complements this vision. He works with people who have already recovered from a viral disease and developed immunity. His team has developed a technology for extracting and replicating monoclonal antibodies (molecules produced by the immune system that target a specific antigen on the virus) from the patient’s blood cells – an extremely effective antidote. “It may not offer lifelong protection, but a couple of months of protection is enough to contain an epidemic,” explains Crowe.
Antibodies that dock, lock onto and block important receptors on the viral surface have already been found for Marburg, Ebola and Zika viruses. “This approach is he best way to combat these pathogens,” says Crowe, and points out the particular speed of the process: “In 2019, we showed in a simulated emergency exercise that we could progress in 78 days from blood sample to completed protection studies,” – that’s only a little over 11 weeks that his team needed to be ready to combat a new virus. “When Covid-19 occurred, we were ready to respond quickly. We isolated best-in-class human monoclonal antibodies from survivor blood cells and passed the antibody combination on to a pharma partner in 25 days,” he adds.
These antibodies formed the basis for AZD7442, a combination of two long-acting antibodies – tixagevimab and cilgavimab. A recent Phase III clinical trial showed that a single 300mg intramuscular dose of AZD7442 reduced the risk of developing symptomatic Covid-19 by 77% compared to a placebo [12].
“We are grateful that Merck KGaA, Darmstadt, Germany set the vision for ‘Pandemic Protector’ in 2019 and supported our work to develop a protector platform. Little did we know that meeting this aspirational goal would occur during a real pandemic less than six months after the start of our Future Insight™ Prize supported work. The timing was amazing.”
At the same time, the research scientist intends to play a role in preventive medicine with his AHEAD100 project. The aim is to develop monoclonal antibodies for 100 known and dangerous virus types that are the most likely causes of future epidemics –so we can be much better prepared before a new outbreak occurs. It was launched formally on August 11, 2021, after an intense 6-month planning phase.
This important initiative has been launched by a large public-private consortium with support from county and state governments, CEPI, the Bill and Melinda Gates Foundation, academic institutions, and many commercial partners.
