NCI has awarded 25 grants and contracts as part of the Serological Sciences Network initiative.
The network, called SeroNet, is designed to increase the nation’s antibody testing capacity and engage the U.S. academic, government and private sector biomedical research institutions in efforts to understand the immune response to COVID-19.
“What seroprevalence levels are needed in a population for herd immunity—and the speculations go all over the map. But suffice it to say that we don’t know,” NCI Principal Deputy Director Douglas R. Lowy said at a press briefing Oct. 8. “Seroprevalence is actually what percentage in a population [has] antibodies. NCI is funding research to address these and related questions through SeroNet, as well as other research—and much of it is in collaboration with the National Institute of Allergy and Infectious diseases and the Centers for Disease Control [and Prevention].”
As part of the Paycheck Protection Program and Health Care Enhancement Act, Congress authorized $306 million for NCI to develop, validate, improve, and implement serological testing and associated technologies. SeroNet is the largest of NCI’s serological science initiatives funded by the COVID-19 emergency appropriation, accounting for more than half of the allocation (The Cancer Letter, June 19, 2020).
Funds were distributed to eight Centers of Excellence, 13 research projects, and four capacity building centers. SeroNet also includes Frederick National Laboratory Serology Lab and one Network Coordinating Center.
“All of the SeroNet components will work closely together, sharing information and resources. Furthermore, all of the publications funded through Seronet will be published in an open access format, and the underlying data made immediately available,” Dinah Singer, head of the Molecular Regulation Section and deputy director for Scientific Strategy and Development at NCI, said at the press briefing.
All the samples and data generated by SeroNet will be made publicly available, she said.
NCI has awarded Serological Centers of Excellence U54 grants to eight institutions, which will conduct research projects that will characterize the immune responses to coronavirus infection and determine what drives immune response, disease progression, and protection against future infection.
Award sizes for the Centers of Excellence range from $815,000 to $2 million each year for the five-year duration of the award.
The eight institutions that received the U54 grants as Centers of Excellence are:
Ohio State University: Center for Serological Testing to Improve Outcomes from Pandemic COVID-19 (STOP-COVID),
University of North Carolina Chapel Hill: North Carolina SeroNet Center for Excellence,
Cedars-Sinai Medical Center: Diversity and Determinants of the Immune-Inflammatory Response to SARS-CoV-2,
Johns Hopkins University: Johns Hopkins Excellence in Pathogenesis and Immunity Center for SARS-CoV-2 (JH-EPICS),
Tulane University: Tulane University COVID Antibody and Immunity Network (TUCAIN),
Stanford University: Mechanisms and Duration of Immunity to SARS-CoV-2,
Emory University: Immune Regulation of COVID-19 Infection in Cancer and Autoimmunity, and
Icahn School of Medicine at Mount Sinai: Vulnerability of SARS- CoV-2 Infection in Lung Cancer Based on Serological Antibody Analyses.
NCI also awarded U01 grants to researchers at 12 institutions to conduct research projects on basic and applied serological research.
“These research projects are smaller in scale and scope. Typically, they’ll be carried out in a single lab,” Singer said.
The award size ranges from $500,000 to $750,000 each year for five years, Singer said.
The 13 institutions that received U01 grants for research projects are:
Wadsworth Center,
Beth Israel Deaconess Medical Center,
Case Western Reserve University for two separate projects,
Kaiser Foundation Research Institute,
Yale University,
Michigan State University,
University of Arkansas for Medical Sciences,
La Jolla Institute for Immunology,
University of Puerto Rico, Medical Sciences,
University of Alabama at Birmingham,
University of Massachusetts Medical School Worchester, and
Harvard School of Public Health.
Also, four Capacity Building Centers were awarded subcontracts through the Frederick National Lab.
“These centers are charged with developing and expanding serological testing capacity and practice in the community. They’ll scale up screening capacity to reach at least 5,000 samples per week with assays that have been granted FDA Emergency Use Authorization,” Singer said. “The centers will also perform long-term studies of the prevalence of COVID-19 across the country.”
The four Capacity Building Centers are:
Arizona State University,
Feinstein Institute for Medical Research,
University of Minnesota, and
Icahn School of Medicine at Mount Sinai.
NCI serology efforts
NCI has developed three serology efforts related to the COVID-19 pandemic (The Cancer Letter, July 24, 2020). In April, the institute began to characterize the performance of many SARS-CoV-2 serology devices submitted to FDA.
In June, NCI started working on a serology dashboard to provide information on antibody testing in the U.S., and in September, the institute began work on a SARS-CoV-2 serum that would be available for use by vaccine manufacturers and by institutions producing convalescent plasma/serum for treating COVID-19 patients.
“This is a work in progress that we just began in September, and we hope sometime next month to be able to have that standard,” Lowy said.
NCI measures specificity of serological devices, Lowy said.
“There has been a remarkable variation, that in some devices that were submitted to FDA, they have been as low as 30%—but some have been as high as 100%. Specificity has varied from 87% to 100%. And specificity means that the device does not detect false positives.”
NCI sends these results to FDA to help the agency determine whether a test is suitable for Emergency Use Authorization. Results are posted at the FDA website once the agency makes that determination.
Based on a summary of 102 commercial serology devices evaluated by FNLCR serology laboratory, if a test has 99% specificity and the seroprevalence rate is found to be 10%:
What seroprevalence levels are needed in a population for herd immunity—and the speculations go all over the map. But suffice it to say that we don’t know.
Douglas Lowy
Ten percent of the positives will be false-positives,
(For 100 tests, nine will be actual positives and one will be false-positive).
If a test has 95% specificity and the seroprevalence rate is found to be 10%:
Fifty percent of the positives will be false-positives,
(For 100 tests, five will be actual positives and five will be false-positive).
Antibody studies can be used to measure seroprevalence, and these tests should be able to identify “virtually everyone who has had symptomatic infection, and most of those who have had asymptomatic infection,” Lowy said. “Antibody tests are not used for diagnosing herd SARS-CoV-2 infection. Diagnostic tests can instead identify parts of the actual virus, either viral RNA, which is most of what’s used, or in some instances, measuring viral protein.”
In June, HHS, CDC and NIAID asked NCI to develop the SARS-CoV-2 Serology Dashboard. The Frederick National Lab has the expertise developing dashboards through the clinical trials reporting system and other databases.
“The key features are to make this a publicly accessible data warehouse that would systematically document and track SARS-CoV-2 serology studies and associated test results, and then to have a tracking dashboard to visualize the serology data and to present the results overall and by key strata,” Lowy said. “We hope it will go live with actual data sometime next month.”
The dashboard will show appropriate data elements through dynamic pop-ups on the dashboard, Lowy said. This could be broken down the level of state, county, or ZIP code.
“We have interacted with a group in Canada that is developing a serological dashboard that is analogous for the world—and our system is designed to be compatible and interoperable with theirs,” Lowy said.
