Rapid Generation of Neutralizing Antibody Responses in COVID-19 Patients

Mehul S Suthar; Matthew G Zimmerman; Robert C Kauffman; Grace Mantus; Susanne L Linderman; William H Hudson; Abigail Vanderheiden; Lindsay Nyhoff; Carl W Davis; Oluwaseyi Adekunle; Maurizio Affer; Melanie Sherman; Stacian Reynolds; Hans P Verkerke; David N Alter; Jeannette Guarner; Janetta Bryksin; Michael C Horwath; Connie M Arthur; Natia Saakadze; Geoffrey H Smith; Srilatha Edupuganti; Erin M Scherer; Kieffer Hellmeister; Andrew Cheng; Juliet A Morales; Andrew S Neish; Sean R Stowell; Filipp Frank; Eric Ortlund; Evan J Anderson; Vineet D Menachery; Nadine Rouphael; Aneesh K Mehta; David S Stephens; Rafi Ahmed; John D Roback; Jens Wrammert

doi:10.1016/j.xcrm.2020.100040

Rapid Generation of Neutralizing Antibody Responses in COVID-19 Patients

Cell Rep Med. 2020 Jun 23;1(3):100040. doi: 10.1016/j.xcrm.2020.100040. Epub 2020 Jun 8.

Authors

Mehul S Suthar^{1

2

3}, Matthew G Zimmerman^{1

2

3}, Robert C Kauffman^{1

2}, Grace Mantus^{1

2}, Susanne L Linderman^{2

4}, William H Hudson^{2

4}, Abigail Vanderheiden^{1

2

3}, Lindsay Nyhoff^{1

2}, Carl W Davis^{2

4}, Oluwaseyi Adekunle^{1

2}, Maurizio Affer^{1

2}, Melanie Sherman⁵, Stacian Reynolds⁵, Hans P Verkerke⁶, David N Alter⁶, Jeannette Guarner⁶, Janetta Bryksin⁶, Michael C Horwath⁶, Connie M Arthur⁶, Natia Saakadze⁶, Geoffrey H Smith⁶, Srilatha Edupuganti^{7

8}, Erin M Scherer^{7

8}, Kieffer Hellmeister^{7

8}, Andrew Cheng^{7

8}, Juliet A Morales^{7

8}, Andrew S Neish⁶, Sean R Stowell⁶, Filipp Frank⁹, Eric Ortlund⁹, Evan J Anderson¹, Vineet D Menachery¹⁰, Nadine Rouphael^{7

8}, Aneesh K Mehta⁸, David S Stephens⁸, Rafi Ahmed^{2

4}, John D Roback⁶, Jens Wrammert^{1

2}

Affiliations

¹ Center for Childhood Infections and Vaccines; Children's Healthcare of Atlanta and Emory University Department of Pediatrics, Atlanta, GA 30322, USA.
² Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30329, USA.
³ Yerkes National Primate Research Center, Atlanta, GA 30329, USA.
⁴ Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
⁵ Emory Medical Laboratories, Emory Healthcare, Atlanta, GA 30322, USA.
⁶ Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
⁷ Hope Clinic of the Emory Vaccine Center, Emory University School of Medicine Decatur, Atlanta, GA, USA.
⁸ Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
⁹ Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, USA.
¹⁰ Department of Microbiology and Immunology, Institute for Human Infection and Immunity, World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX, USA.

Abstract

SARS-CoV-2, the virus responsible for COVID-19, is causing a devastating worldwide pandemic, and there is a pressing need to understand the development, specificity, and neutralizing potency of humoral immune responses during acute infection. We report a cross-sectional study of antibody responses to the receptor-binding domain (RBD) of the spike protein and virus neutralization activity in a cohort of 44 hospitalized COVID-19 patients. RBD-specific IgG responses are detectable in all patients 6 days after PCR confirmation. Isotype switching to IgG occurs rapidly, primarily to IgG1 and IgG3. Using a clinical SARS-CoV-2 isolate, neutralizing antibody titers are detectable in all patients by 6 days after PCR confirmation and correlate with RBD-specific binding IgG titers. The RBD-specific binding data were further validated in a clinical setting with 231 PCR-confirmed COVID-19 patient samples. These findings have implications for understanding protective immunity against SARS-CoV-2, therapeutic use of immune plasma, and development of much-needed vaccines.

Keywords: COVID-19; SARS-CoV-2; coronavirus; humoral immune response; neutralizing antibody; protective immunity; receptor-binding protein; serology test; spike protein.

Abstract

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