Pandemic's urgency drove new collaborative approaches worldwide
SAVE team changed how science is done, spanning 58 institutions

Date:
April 1, 2022
Source:
DOE/Los Alamos National Laboratory
Summary:
In a new paper, nearly 130 authors from institutions around the
world describe their groundbreaking collaborative work, 'Defining
the risk of SARS-CoV-2 variants on immune protection.'


FULL STORY ==========================================================================
In a paper 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 rarified 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 fields such as viruses, the immune system, vaccines, epidemiology, structural biology, bioinformatics, virus genetics,
and evolution. The team is called SAVE, for SARS-CoV-2 Assessment of
Viral Evolution.

As noted in the Nature paper, the authors state, "This effort was designed
to provide a real-time risk assessment of SARS-CoV-2 variants potentially impacting 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 SARS-CoV-2 Interagency Group to assess implications of SARS-CoV-2 variants on
diagnostics, vaccines and therapeutics and for communicating public
health risk." Broad model for rapid response SAVE focuses on mutations
in SARS-CoV-2 and emerging virus variants. But its members say the global collaborative concept "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, that have threatened global public health," the paper's summary states. "Developing collaborative programs
between academic, industry and commercial partners is essential to
respond to rapidly evolving viruses," said Marciela DeGrace of NIAID,
the paper's lead author.



==========================================================================
SAVE members represent 58 different research sites located in the United
States and around the world. Members participate within 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 such high-impact work as the initial identification
of mutations in the virus made waves in the scientific community before
its capacity for mutation had been clearly understood and accepted.

The Nature paper notes, "The process is collaborative and iterative, with
seven teams using independent models and methodologies to prioritize
mutations and lineages as well as rank importance for downstream
testing. While the focus is on human infections, the Early Detection
group also monitors variants circulating in animal populations, such
as mink and deer, since they represent a potential reservoir source."
On a weekly basis, the SAVE Early Detection and Analysis team reviews
downloads of SARS-CoV-2 genomes from the international initiative
for sequence sharing, GISAID. They search for variant and co-variant
signatures in the genomes, then divide the work into two approaches:
* one based on convergent evolution as the main signal for selection
and
functional impact of mutations (done byCambridge and Walter Reed
Army Institute of Research teams)
* the other anchored on prevalence and growth patterns of mutations
and
defined lineages (the role ofLos Alamos, Icahn School of Medicine at
Mount Sinai, J. Craig Venter Institute/Bacterial Viral Bioinformatic
Resource Center, UC-Riverside and Broad Institute teams)
Highlights of Los Alamos impact


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

They pay particular attention to mutations in parts of the spike
protein known to be highly targeted by antibodies, or that might impact infectivity. They also systematically define the most commonly circulating
form of each emerging variant of interest or concern against the backdrop
of the continuously evolving virus.

"Identifying the emerging variants, and obtaining accurate sequences
for those variants, required continued wrangling of burgeoning data,"
said Theiler.

"There are now close to 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 newest variants that give
the sequencers the most trouble." "The tools we developed, along with
our colleagues on the LANL COVID-19 Viral Genome Analysis Pipeline (cov.lanl.gov), provided the infrastructure that enabled us to follow
this pandemic though its various waves," he added.

Korber noted that "by working with the SAVE Early Detection team, we
were able to be part of a synergistic collaborative effort, where our
results in terms of early detection could be cross-checked with those
of others." She added, "The real beauty of being part of the larger
SAVE project was the knowledge that our analysis pipeline could provide foundational support for the many experimental teams in SAVE, and that
we could help the scientific community get the best version of newly
emergent 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."

========================================================================== Story Source: Materials provided by
DOE/Los_Alamos_National_Laboratory. Note: Content may be edited for
style and length.


========================================================================== Journal Reference:
1. Marciela M. DeGrace, Elodie Ghedin, Matthew B. Frieman, Florian
Krammer,
Alba Grifoni, Arghavan Alisoltani, Galit Alter, Rama R. Amara,
Ralph S.

Baric, Dan H. Barouch, Jesse D. Bloom, Louis-Marie Bloyet, Gaston
Bonenfant, Adrianus C. M. Boon, Eli A. Boritz, Debbie L. Bratt,
Traci L.

Bricker, Liliana Brown, William J. Buchser, Juan Manuel Carren~o,
Liel Cohen-Lavi, Tamarand L. Darling, Meredith E. Davis-Gardner,
Bethany L.

Dearlove, Han Di, Meike Dittmann, Nicole A. Doria-Rose, Daniel
C. Douek, Christian Drosten, Venkata-Viswanadh Edara, Ali Ellebedy,
Thomas P.

Fabrizio, Guido Ferrari, William C. Florence, Ron A. M. Fouchier,
John Franks, Adolfo Garci'a-Sastre, Adam Godzik, Ana Silvia
Gonzalez-Reiche, Aubree Gordon, Bart L. Haagmans, Peter J. Halfmann,
David D. Ho, Michael R. Holbrook, Yaoxing Huang, Sarah L. James,
Lukasz Jaroszewski, Trushar Jeevan, Robert M. Johnson, Terry
C. Jones, Astha Joshi, Yoshihiro Kawaoka, Lisa Kercher, Marion
P. G. Koopmans, Bette Korber, Eilay Koren, Richard A. Koup, Eric
B. LeGresley, Jacob E. Lemieux, Mariel J.

Liebeskind, Zhuoming Liu, Brandi Livingston, James P. Logue,
Yang Luo, Adrian B. McDermott, Margaret J. McElrath, Victoria
A. Meliopoulos, Vineet D. Menachery, David C. Montefiori, Barbara
Mu"hlemann, Vincent J.

Munster, Jenny E. Munt, Manoj S. Nair, Antonia Netzl, Anna M.

Niewiadomska, Sijy O'Dell, Andrew Pekosz, Stanley Perlman,
Marjorie C.

Pontelli, Barry Rockx, Morgane Rolland, Paul W. Rothlauf, Sinai
Sacharen, Richard H. Scheuermann, Stephen D. Schmidt, Michael
Schotsaert, Stacey Schultz-Cherry, Robert A. Seder, Mayya Sedova,
Alessandro Sette, Reed S.

Shabman, Xiaoying Shen, Pei-Yong Shi, Maulik Shukla, Viviana
Simon, Spencer Stumpf, Nancy J. Sullivan, Larissa B. Thackray,
James Theiler, Paul G. Thomas, Sanja Trifkovic, Sina Tu"reli,
Samuel A. Turner, Maria A.

Vakaki, Harm van Bakel, Laura A. VanBlargan, Leah R. Vincent,
Zachary S.

Wallace, Li Wang, Maple Wang, Pengfei Wang, Wei Wang, Scott
C. Weaver, Richard J. Webby, Carol D. Weiss, David E. Wentworth,
Stuart M. Weston, Sean P. J. Whelan, Bradley M. Whitener, Samuel
H. Wilks, Xuping Xie, Baoling Ying, Hyejin Yoon, Bin Zhou, Tomer
Hertz, Derek J. Smith, Michael S. Diamond, Diane J. Post, Mehul
S. Suthar. Defining the risk of SARS- CoV-2 variants on immune
protection. Nature, 2022; DOI: 10.1038/s41586- 022-04690-5 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/04/220401141340.htm

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