Sci Rep . Plasmodium infection is associated with cross-reactive antibodies to carbohydrate epitopes on the SARS-CoV-2 Spike protein

[tetano]

Sci Rep


. 2022 Dec 22;12(1):22175.
doi: 10.1038/s41598-022-26709-7.
Plasmodium infection is associated with cross-reactive antibodies to carbohydrate epitopes on the SARS-CoV-2 Spike protein


Sarah Lapidus ¹ , Feimei Liu ² , Arnau Casanovas-Massana ¹ , Yile Dai ² , John D Huck ² , Carolina Lucas ² , Jon Klein ² , Renata B Filler ^{2 3} , Madison S Strine ^{2 3} , Mouhamad Sy ^{1 4} , Awa B Deme ^{1 4} , Aida S Badiane ⁴ , Baba Dieye ⁴ , Ibrahima Mbaye Ndiaye ⁴ , Younous Diedhiou ⁴ , Amadou Moctar Mbaye ⁴ , Cheikh Tidiane Diagne ⁵ , Inés Vigan-Womas ⁶ , Alassane Mbengue ⁷ , Bacary D Sadio ⁸ , Moussa M Diagne ⁸ , Adam J Moore ¹ , Khadidiatou Mangou ⁷ , Fatoumata Diallo ⁷ , Seynabou D Sene ⁷ , Mariama N Pouye ⁷ , Rokhaya Faye ⁶ , Babacar Diouf ⁶ , Nivison Nery Jr ^{9 10} , Federico Costa ^{1 9 11} , Mitermayer G Reis ^{1 11 12} , M Catherine Muenker ¹ , Daniel Z Hodson ¹ , Yannick Mbarga ¹³ , Ben Z Katz ¹⁴ , Jason R Andrews ¹⁵ , Melissa Campbell ¹⁶ , Ariktha Srivathsan ¹ , Kathy Kamath ¹⁷ , Elisabeth Baum-Jones ¹⁷ , Ousmane Faye ⁸ , Amadou Alpha Sall ⁸ , Juan Carlos Quintero Vélez ^{1 18 19} , Michael Cappello ^{1 20} , Michael Wilson ²¹ , Choukri Ben-Mamoun ²² , Richard Tedder ^{23 24} , Myra McClure ²³ , Peter Cherepanov ^{23 25 26} , Fabrice A Somé ²⁷ , Roch K Dabiré ²⁷ , Carole Else Eboumbou Moukoko ^{28 29} , Jean Bosco Ouédraogo ²⁷ , Yap Boum 2nd ³⁰ , John Shon ¹⁷ , Daouda Ndiaye ⁴ , Adam Wisnewski ¹⁰ , Sunil Parikh ¹ , Akiko Iwasaki ^{1 2 31} , Craig B Wilen ² , Albert I Ko ^{1 11} , Aaron M Ring ² , Amy K Bei ^{32 33 34}



Affiliations

• PMID: 36550362
• DOI: 10.1038/s41598-022-26709-7

Abstract

Sero-surveillance can monitor and project disease burden and risk. However, SARS-CoV-2 antibody test results can produce false positive results, limiting their efficacy as a sero-surveillance tool. False positive SARS-CoV-2 antibody results are associated with malaria exposure, and understanding this association is essential to interpret sero-surveillance results from malaria-endemic countries. Here, pre-pandemic samples from eight malaria endemic and non-endemic countries and four continents were tested by ELISA to measure SARS-CoV-2 Spike S1 subunit reactivity. Individuals with acute malaria infection generated substantial SARS-CoV-2 reactivity. Cross-reactivity was not associated with reactivity to other human coronaviruses or other SARS-CoV-2 proteins, as measured by peptide and protein arrays. ELISAs with deglycosylated and desialated Spike S1 subunits revealed that cross-reactive antibodies target sialic acid on N-linked glycans of the Spike protein. The functional activity of cross-reactive antibodies measured by neutralization assays showed that cross-reactive antibodies did not neutralize SARS-CoV-2 in vitro. Since routine use of glycosylated or sialated assays could result in false positive SARS-CoV-2 antibody results in malaria endemic regions, which could overestimate exposure and population-level immunity, we explored methods to increase specificity by reducing cross-reactivity. Overestimating population-level exposure to SARS-CoV-2 could lead to underestimates of risk of continued COVID-19 transmission in sub-Saharan Africa.