The SAVE team has changed the way science is practiced, spanning 58 institutions

In an article in the journal Nature, Los Alamos National Laboratory scientists Bette Korber, Hyejin Yoon, Will Fischer, and James Theiler, among nearly 130 authors from institutions around the world, describe their groundbreaking collaborative work, “Defining the risk of SARS-CoV-2 variants on immune protection.”

Korber, Fischer, Yoon and Theiler are members of a rarefied team that the National Institute of Allergy and Infectious Diseases assembled in January 2021, drawing on experts from around the world who specialize in relevant research areas such as viruses, the immune system, vaccines, epidemiology, structural biology, bioinformatics, viral genetics and evolution. The team is called SAVE, for SARS-CoV-2 Assessment of Viral Evolution.

As noted in the Nature article, the authors state, “This effort was designed to provide a real-time risk assessment of SARS-CoV-2 variants with potential impact on transmission, virulence, and resistance to convalescent and vaccine-induced immunity.The SAVE program serves as a critical data-generating component of the United States Government’s SARS-CoV-2 Interagency Group to assess the implications of SARS-CoV-2 variants on diagnostics, vaccines and treatments and to communicate public health risks.

Wide pattern for quick response

SAVE focuses on SARS-CoV-2 mutations and emerging viral variants. But its members say the concept of global collaboration “is a broad model for rapidly responding to evolving pathogens with pandemic potential.”

“Over the past two decades, we have witnessed the emergence/re-emergence of several RNA viruses, including West Nile virus, H1N1 influenza virus, chikungunya virus, Zika virus, SARS-CoV -1, MERS-CoV, and Ebola virus, which have threatened global public health,” the document’s abstract states. “The development of collaborative programs between academic, industrial, and commercial partners is essential to respond to evolving viruses. fast,” said NIAID’s Marciela DeGrace, the paper’s lead author.

SAVE members represent 58 different research sites located in the United States and around the world. Members participate in three sub-groups:

  • Early detection and analysis
  • In Vitro – what they can learn using flasks, beakers and tubes
  • In Vivo – what they can learn in animal models that mimic human disease

Early detection methods

Korber’s team was part of the early detection and analysis team, where high-impact work such as the initial identification of virus mutations made waves in the scientific community before its ability to mutate n has been clearly understood and accepted.

The Nature article notes: “The process is collaborative and iterative, with seven teams using independent models and methodologies to prioritize mutations and lineages as well as rank the importance of downstream testing. While the focus is focused on human infections, the early detection group also monitors variants circulating in animal populations, such as mink and deer, as they represent a potential reservoir source.”

Each week, the SAVE Early Detection and Analysis team reviews SARS-CoV-2 genome uploads from the international initiative for sequence sharing, GISAID. They search for variant and covariant signatures in genomes, then divide the work into two approaches:

  • one based on convergent evolution as the main signal for selection and the functional impact of mutations (carried out by teams from Cambridge and the Walter Reed Army Institute of Research)
  • the other anchored on the prevalence and growth patterns of mutations and defined lineages (the role of Los Alamos, Icahn School of Medicine at Mount Sinai, J. Craig Venter Institute/Bacterial Viral Bioinformatic Resource Center, UC-Riverside and Broad Institute teams)

Los Alamos Impact Highlights

At Los Alamos, the Korber team is identifying emerging mutational patterns within the SARS-CoV-2 spike protein to track emerging and expanding variants and determine transitions in global and regional sampling frequencies over time. time, which is the specialty area in which Los Alamos made a huge impact.

They pay particular attention to mutations in parts of the spike protein known to be highly targeted by antibodies, or which could impact infectivity. They also systematically define the most commonly circulating form of each emerging variant of interest or concern in the context of the continued evolution of the virus.

“Identifying emerging variants and obtaining accurate sequences for those variants has required an ongoing battle for burgeoning data,” Theiler said. “There are now nearly 10 million SARS-CoV-2 sequences in GISAID. These sequences, however, are non-uniformly sampled, are often partial and some contain errors, and of course it is the newer variants that give the sequencers the most. worry.”

“The tools we developed, together with our colleagues in the LANL COVID-19 Viral Genome Analysis Pipeline (cov.lanl.gov), provided the infrastructure that allowed us to follow this pandemic through its various waves” , he added.

Korber noted that “by working with SAVE’s early detection team, we were able to be part of a synergistic collaborative effort, where our early detection results could be cross-checked with those of others.”

She added, “The real beauty of being part of the larger SAVE project was knowing that our analytics pipeline could provide foundational support to the many experimental SAVE teams, and that we could help the scientific community get the best version newly emerging variants into their laboratories as quickly and accurately as possible.In this way, the science needed to understand the immunological and virological characteristics of new variants was rapidly obtained, in time to help inform public health decisions.