Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Assessment of the Humoral Immune Response to the SARS-CoV-2 Spike Protein Receptor Binding Motif

Maria E.S. Monteiro
ORCID logo ,
Guilherme C Lechuga
,
Larisa R Gomes
,
João PRS Carvalho
,
Paloma Napoleão-Pêgo
,
Carlos M Morel
ORCID logo ,
David W Provance-Jr
,
Salvatore G De-Simone
* ORCID logo
Version 1 : Received: 3 November 2023 / Approved: 3 November 2023 / Online: 7 November 2023 (11:27:48 CET)

How to cite: Monteiro, M.E.; Lechuga, G.C.; Gomes, L.R.; Carvalho, J.P.; Napoleão-Pêgo, P.; Morel, C.M.; Provance-Jr, D.W.; De-Simone, S.G. Assessment of the Humoral Immune Response to the SARS-CoV-2 Spike Protein Receptor Binding Motif. Preprints 2023, 2023110296. https://doi.org/10.20944/preprints202311.0296.v1 Monteiro, M.E.; Lechuga, G.C.; Gomes, L.R.; Carvalho, J.P.; Napoleão-Pêgo, P.; Morel, C.M.; Provance-Jr, D.W.; De-Simone, S.G. Assessment of the Humoral Immune Response to the SARS-CoV-2 Spike Protein Receptor Binding Motif. Preprints 2023, 2023110296. https://doi.org/10.20944/preprints202311.0296.v1

Abstract

Global economic and social burden was caused by the SARS-CoV-2 spread worldwide. Despite the end of the pandemic, there is a concern about virulent evolving variants of the virus which can bypass the humoral immune response induced by vaccination or infection. Crucial to the viral entrance, amino acid residues in the RBM region, which interacts with cellular receptor ACE2, can elicit neutralizing antibody response. Herein we determine the immunogenicity of one-dose or heterologous dose vaccinated serum against wild-type and mutated RBM region. Despite low antibody response to wild-type SARS-CoV-2 RBM, omicron variants possess four mutations in RBM (S477N, T478K, E484A, F486V) that induce even less antibody titers. The most predominant responses were against IgA and IgG. While neutralizing antibodies (nAbs) predominantly target the RBD, our investigation revealed a diminished seroreactivity within the RBD's crucial region, the receptor-binding motif (RBM), potentially impacting the production of protective nAbs. S1WT and S2WT RBM peptides binding to nAbs were evaluated through microscale thermophoresis, and higher affinity (35 nM) was obtained for sequence S2WT (GSTPCNGVEGFNCYF), containing the FNCY patch. Our data indicates that SARS-CoV-2 RBM is not an immunodominant region in vaccinated individuals. Understanding the intricate dynamics of the humoral response and its interplay with viral evolution and host genetics is essential for the formulation of effective vaccination strategies, not only against SARS-CoV-2 but also for future emerging coronaviruses.

Keywords

SARS-CoV-2; Variants; Spike Glycoprotein; Receptor Binding Motif, Receptor Binding Domain; Neutralizing Antibodies; Ig subclasses; IgG; IgA

Subject

Biology and Life Sciences, Biology and Biotechnology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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