. 2021 Nov 21;13(11):2325.

doi: 10.3390/v13112325.

Cross-Reactive Antibodies to SARS-CoV-2 and MERS-CoV in Pre-COVID-19 Blood Samples from Sierra Leoneans

Rodrigo Borrega¹, Diana K S Nelson², Anatoliy P Koval¹, Nell G Bond³, Megan L Heinrich¹, Megan M Rowland¹, Raju Lathigra¹, Duane J Bush², Irina Aimukanova², Whitney N Phinney², Sophia A Koval¹, Andrew R Hoffmann³, Allison R Smither³, Antoinette R Bell-Kareem³, Lilia I Melnik³, Kaylynn J Genemaras^{3

4}, Karissa Chao^{3

4}, Patricia Snarski^{5

6}, Alexandra B Melton⁷, Jaikin E Harrell³, Ashley A Smira⁸, Debra H Elliott⁸, Julie A Rouelle⁸, Gilberto Sabino-Santos Jr^{9

10}, Arnaud C Drouin¹¹, Mambu Momoh^{12

13

14}, John Demby Sandi¹³, Augustine Goba¹³, Robert J Samuels¹³, Lansana Kanneh¹³, Michael Gbakie¹³, Zoe L Branco¹, Jeffrey G Shaffer¹⁵, John S Schieffelin^{8

16}, James E Robinson⁸, Dahlene N Fusco¹¹, Pardis C Sabeti^{17

18

19

20

21

22}, Kristian G Andersen^{23

24}, Donald S Grant^{13

14}, Matthew L Boisen², Luis M Branco¹, Robert F Garry^{1

2

3}

Affiliations

¹ Zalgen Labs, LCC, Germantown, MD 20876, USA.
² Zalgen Labs, LCC, Broomfield, CO 80045, USA.
³ Department of Microbiology and Immunology, School of Medicine, Tulane University, New Orleans, LA 70112, USA.
⁴ Bioinnovation Program, Tulane University, New Orleans, LA 70118, USA.
⁵ Heart and Vascular Institute, John W. Deming Department of Medicine, School of Medicine, Tulane University, New Orleans, LA 70112, USA.
⁶ Department of Physiology, School of Medicine, Tulane University, New Orleans, LA 70112, USA.
⁷ Department of Microbiology, Tulane National Primate Research Center, Covington, LA 70433, USA.
⁸ Department of Pediatrics, School of Medicine, Tulane University, New Orleans, LA 70112, USA.
⁹ Department of Tropical Medicine, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA 70112, USA.
¹⁰ Centre for Virology Research, Ribeirão Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, SP, Brazil.
¹¹ Department of Medicine, School of Medicine, Tulane University, New Orleans, LA 70112, USA.
¹² Eastern Polytechnic Institute, Kenema, Sierra Leone.
¹³ Viral Hemorrhagic Fever Program, Kenema Government Hospital, Kenema, Sierra Leone.
¹⁴ Ministry of Health and Sanitation, Freetown, Sierra Leone.
¹⁵ Department of Biostatistics and Data Science, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA 70112, USA.
¹⁶ Department of Internal Medicine, School of Medicine, Tulane University, New Orleans, LA 70112, USA.
¹⁷ Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA 02142, USA.
¹⁸ Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
¹⁹ Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA.
²⁰ Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA 02115, USA.
²¹ Department of Medicine, Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA 02114, USA.
²² Massachusetts Consortium on Pathogen Readiness, Boston, MA 02115, USA.
²³ Department of Immunology and Microbial Science, Scripps Research, La Jolla, CA 92037, USA.
²⁴ Scripps Research Translational Institute, La Jolla, CA 92037, USA.

PMID: 34835131
PMCID: PMC8625389
DOI: 10.3390/v13112325

Cross-Reactive Antibodies to SARS-CoV-2 and MERS-CoV in Pre-COVID-19 Blood Samples from Sierra Leoneans

Rodrigo Borrega et al. Viruses. 2021.

. 2021 Nov 21;13(11):2325.

doi: 10.3390/v13112325.

Authors

Affiliations

¹ Zalgen Labs, LCC, Germantown, MD 20876, USA.
² Zalgen Labs, LCC, Broomfield, CO 80045, USA.
³ Department of Microbiology and Immunology, School of Medicine, Tulane University, New Orleans, LA 70112, USA.
⁴ Bioinnovation Program, Tulane University, New Orleans, LA 70118, USA.
⁵ Heart and Vascular Institute, John W. Deming Department of Medicine, School of Medicine, Tulane University, New Orleans, LA 70112, USA.
⁶ Department of Physiology, School of Medicine, Tulane University, New Orleans, LA 70112, USA.
⁷ Department of Microbiology, Tulane National Primate Research Center, Covington, LA 70433, USA.
⁸ Department of Pediatrics, School of Medicine, Tulane University, New Orleans, LA 70112, USA.
⁹ Department of Tropical Medicine, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA 70112, USA.
¹⁰ Centre for Virology Research, Ribeirão Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, SP, Brazil.
¹¹ Department of Medicine, School of Medicine, Tulane University, New Orleans, LA 70112, USA.
¹² Eastern Polytechnic Institute, Kenema, Sierra Leone.
¹³ Viral Hemorrhagic Fever Program, Kenema Government Hospital, Kenema, Sierra Leone.
¹⁴ Ministry of Health and Sanitation, Freetown, Sierra Leone.
¹⁵ Department of Biostatistics and Data Science, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA 70112, USA.
¹⁶ Department of Internal Medicine, School of Medicine, Tulane University, New Orleans, LA 70112, USA.
¹⁷ Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA 02142, USA.
¹⁸ Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
¹⁹ Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA.
²⁰ Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA 02115, USA.
²¹ Department of Medicine, Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA 02114, USA.
²² Massachusetts Consortium on Pathogen Readiness, Boston, MA 02115, USA.
²³ Department of Immunology and Microbial Science, Scripps Research, La Jolla, CA 92037, USA.
²⁴ Scripps Research Translational Institute, La Jolla, CA 92037, USA.

PMID: 34835131
PMCID: PMC8625389
DOI: 10.3390/v13112325

Abstract

Many countries in sub-Saharan Africa have experienced lower COVID-19 caseloads and fewer deaths than countries in other regions worldwide. Under-reporting of cases and a younger population could partly account for these differences, but pre-existing immunity to coronaviruses is another potential factor. Blood samples from Sierra Leonean Lassa fever and Ebola survivors and their contacts collected before the first reported COVID-19 cases were assessed using enzyme-linked immunosorbent assays for the presence of antibodies binding to proteins of coronaviruses that infect humans. Results were compared to COVID-19 subjects and healthy blood donors from the United States. Prior to the pandemic, Sierra Leoneans had more frequent exposures than Americans to coronaviruses with epitopes that cross-react with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), SARS-CoV, and Middle Eastern respiratory syndrome coronavirus (MERS-CoV). The percentage of Sierra Leoneans with antibodies reacting to seasonal coronaviruses was also higher than for American blood donors. Serological responses to coronaviruses by Sierra Leoneans did not differ by age or sex. Approximately a quarter of Sierra Leonian pre-pandemic blood samples had neutralizing antibodies against SARS-CoV-2 pseudovirus, while about a third neutralized MERS-CoV pseudovirus. Prior exposures to coronaviruses that induce cross-protective immunity may contribute to reduced COVID-19 cases and deaths in Sierra Leone.

Keywords: COVID-19 caseloads and deaths; Middle Eastern respiratory syndrome coronavirus; enzyme-linked immunosorbent assays; pre-existing immunity to coronaviruses; pseudovirus neutralizing antibodies; recombinant antigens; severe acute respiratory syndrome coronavirus-2; sub-Saharan Africa.

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Conflict of interest statement

L.M.B. and R.F.G. are co-founders of Zalgen Labs, a biotechnology company developing countermeasures for emerging viruses. R.B., D.S.K.N., A.P.K., M.L.H., M.M.R., R.J., D.J.B., I.A., W.N.P., S.A.K., Z.L.B. and M.L.B. are employees of Zalgen Labs. All other authors declare no conflict of interest.

Figures

**Figure 1**
Recombinant coronavirus proteins. (A) Nucleoprotein (N) from SARS-CoV expressed in *E. coli*, purified, and proteins in selected fractions were resolved by sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE). (B) SARS-CoV-2 nucleoprotein was expressed in *E. coli*, purified, and resolved by SDS-PAGE as described for SARS-CoV. Monomeric forms of the protein (asterisks) and a breakdown product were detected. (C) SARS-CoV-2 receptor binding domain was expressed in Expi293 cells, purified, and resolved by SDS-PAGE for (D) SARS-CoV N, hCoV-NL63 N, hCoV-229E N, MERS-CoV, and (E) hCoV-OC43 N. Vertical lines indicate removal of lanes from a gel. Asterisk (*): monomeric N or RBD. Uncropped polyacrylamide gel D is shown in Figure S1.

**Figure 2**
Serological responses to coronavirus antigens by Sierra Leoneans, COVID-19 subjects, and United States normal blood donors. The percentage of positive results for the indicated coronavirus proteins for the three cohorts are shown: (A) SARS-CoV-2 N, (B) SARS-CoV-2 RBD, (C) MERS-CoV-N, (D) hCoV-229E N, (E) hCoV-NL63 N, and (F) hCoV-OC43 N.

**Figure 3**
Correlations of the serological responses of Sierra Leoneans to coronavirus antigens. Binding of IgG in serum or plasma samples (1:100 dilution) from Sierra Leoneans was quantified using ELISA coated with recombinant coronavirus proteins. Reactivity to SARS-CoV-2 N was compared to other coronavirus proteins in each panel: (A) SARS-CoV N, (B) SARS-CoV-2 RBD, (C) MERS-CoV-N, (D) hCoV-229E N, (E) hCoV-NL63 N, and (F) hCoV-OC43 N. Dotted lines are linear regression plots of seroreactivity of SARS-CoV-2 N versus other recombinant coronavirus proteins. PC = Pearson’s correlation.

**Figure 4**
Correlations of the serological responses of COVID-19 subjects to coronavirus antigens. Binding of IgG in serum or plasma samples (1:100 dilution) from COVID-19 subjects was quantified using ELISA coated with recombinant coronavirus proteins. Reactivity to SARS-CoV-2 N was compared to other coronavirus proteins in each panel: (A) SARS-CoV N, (B) SARS-CoV-2 RBD, (C) MERS-CoV-N, (D) hCoV-229E N, (E) hCoV-NL63 N, and (F) hCoV-OC43 N. Dotted lines are linear regression plots of seroreactivity of SARS-CoV-2 N versus other recombinant coronavirus proteins. PC = Pearson’s correlation.

**Figure 5**
Correlations of the serological responses of United States normal blood donors to coronavirus antigens. Binding of IgG in serum or plasma samples (1:100 dilution) from United States normal blood donors was quantified using ELISA coated with recombinant coronavirus proteins. Reactivity to SARS-CoV-2 N was compared to other coronavirus proteins in each panel: (A) SARS-CoV N, (B) SARS-CoV-2 RBD, (C) MERS-CoV-N, (D) hCoV-229E N, (E) hCoV-NL63 N, and (F) hCoV-OC43 N. Dotted lines are linear regression plots of seroreactivity of SARS-CoV-2 N versus other recombinant coronavirus proteins. PC = Pearson’s correlation.

**Figure 6**
Neutralization of pseudoviruses expressing SARS-CoV-2 and MERS-CoV spike. SARS-CoV-2 pseudovirus neutralization curves were determined with samples from the following subjects: (A) SL22, (B) SL 73, and (C) SL83. MERS-CoV pseudovirus neutralization curves were determined with samples from the following subjects: (D) SL9, (E) SL36, and (F) SL 80.

**Figure 7**
Sequence identity and similarity of nucleocapsid and spike across the *Coronaviridae* family. The percentage of identical and chemically similar amino acids are indicated in (A) across the entire N proteins. Shading is proportional to the percent identity or similarity. (B) shows the amino terminal (N-term) sequences of the N proteins. (C) shows the carboxyl-terminal (C-term) sequences of the N proteins (D) across the entire spike proteins. (E) S1 subunit sequence of the S proteins and (F) S2 subunit sequence of the S proteins.

See this image and copyright information in PMC

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Cross-Reactive Antibodies to SARS-CoV-2 and MERS-CoV in Pre-COVID-19 Blood Samples from Sierra Leoneans

Affiliations

Cross-Reactive Antibodies to SARS-CoV-2 and MERS-CoV in Pre-COVID-19 Blood Samples from Sierra Leoneans

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

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Substances

Grants and funding

LinkOut - more resources

Full Text Sources

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Medical

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