Direct capture of neutralized RBD enables rapid point-of-care assessment of SARS-CoV-2 neutralizing antibody titer

Guinevere G Connelly; Orville O Kirkland; Seven Bohannon; Daniel C Lim; Robert M Wilson; Edward J Richards; Dousabel M Tay; Hyuk Jee; Riley D Hellinger; Ngoc K Hoang; Liang Hao; Arnav Chhabra; Carmen Martin-Alonso; Edward K W Tan; Angela N Koehler; Michael B Yaffe; Wendy B London; Pui Y Lee; Florian Krammer; Robert C Bohannon; Sangeeta N Bhatia; Hadley D Sikes; Hojun Li

doi:10.1016/j.crmeth.2022.100273

Direct capture of neutralized RBD enables rapid point-of-care assessment of SARS-CoV-2 neutralizing antibody titer

Cell Rep Methods. 2022 Aug 22;2(8):100273. doi: 10.1016/j.crmeth.2022.100273. Epub 2022 Aug 4.

Authors

Guinevere G Connelly¹, Orville O Kirkland¹, Seven Bohannon², Daniel C Lim¹, Robert M Wilson^{1

3}, Edward J Richards^{1

4}, Dousabel M Tay⁵, Hyuk Jee⁶, Riley D Hellinger¹, Ngoc K Hoang¹, Liang Hao¹, Arnav Chhabra^{1

7}, Carmen Martin-Alonso¹, Edward K W Tan¹, Angela N Koehler^{1

3

8}, Michael B Yaffe^{1

3

9}, Wendy B London^{10

11

12}, Pui Y Lee^{6

12}, Florian Krammer¹³, Robert C Bohannon², Sangeeta N Bhatia^{1

8

14

15

16

17

18}, Hadley D Sikes⁵, Hojun Li^{1

10

11

12}

Affiliations

¹ Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
² Catalloid Products, Elkhart, IN 46514, USA.
³ Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
⁴ Dragonfly Therapeutics, Waltham, MA 02451, USA.
⁵ Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
⁶ Division of Rheumatology, Boston Children's Hospital, Boston, MA 02115, USA.
⁷ Satellite Bio, Cambridge, MA 02139, USA.
⁸ Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
⁹ Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
¹⁰ Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA.
¹¹ Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
¹² Harvard Medical School, Boston, MA 02115, USA.
¹³ Department of Microbiology, and Department of Pathology, Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
¹⁴ Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139, USA.
¹⁵ Institute for Medical Engineering and Science, and Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
¹⁶ Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
¹⁷ Howard Hughes Medical Institute, Cambridge, MA 02139, USA.
¹⁸ Wyss Institute at Harvard, Boston, MA 02115, USA.

Abstract

Neutralizing antibody (NAb) titer is a key biomarker of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but point-of-care methods for assessing NAb titer are not widely available. Here, we present a lateral flow assay that captures SARS-CoV-2 receptor-binding domain (RBD) that has been neutralized from binding angiotensin-converting enzyme 2 (ACE2). Quantification of neutralized RBD in this assay correlates with NAb titer from vaccinated and convalescent patients. This methodology demonstrated superior performance in assessing NAb titer compared with either measurement of total anti-spike immunoglobulin G titer or quantification of the absolute reduction in binding between ACE2 and RBD. Our testing platform has the potential for mass deployment to aid in determining at population scale the degree of protective immunity individuals may have following SARS-CoV-2 vaccination or infection and can enable simple at-home assessment of NAb titer.

Keywords: ACE2; LFA; POC diagnostics; RBD; SARS-CoV-2; neutralizing antibodies.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Angiotensin-Converting Enzyme 2
Antibodies, Neutralizing*
Antibodies, Viral
COVID-19 Vaccines
COVID-19* / diagnosis
Humans
Point-of-Care Systems
SARS-CoV-2

Substances

Antibodies, Neutralizing
Angiotensin-Converting Enzyme 2
COVID-19 Vaccines
Antibodies, Viral

Abstract

Publication types

MeSH terms

Substances

Grants and funding