Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Humoral Immune Response to the SARS-CoV-2 Spike Protein Receptor Binding Motif Linear Epitopes

Maria E.S. Monteiro
ORCID logo ,
Guilherme C. Lechuga
,
Paloma Napoleão-Pêgo
,
João P. R. S. Carvalho
,
Larissa R Gomes
,
Carlos M. Morel
ORCID logo ,
D. William Provance, Jr.
* ,
Salvatore G. De-Simone
* ORCID logo
Version 1 : Received: 1 February 2024 / Approved: 1 February 2024 / Online: 2 February 2024 (07:31:35 CET)

A peer-reviewed article of this Preprint also exists.

Monteiro, M.E.S.; Lechuga, G.C.; Napoleão-Pêgo, P.; Carvalho, J.P.R.S.; Gomes, L.R.; Morel, C.M.; Provance, D.W.; De-Simone, S.G. Humoral Immune Response to SARS-CoV-2 Spike Protein Receptor-Binding Motif Linear Epitopes. Vaccines 2024, 12, 342. Monteiro, M.E.S.; Lechuga, G.C.; Napoleão-Pêgo, P.; Carvalho, J.P.R.S.; Gomes, L.R.; Morel, C.M.; Provance, D.W.; De-Simone, S.G. Humoral Immune Response to SARS-CoV-2 Spike Protein Receptor-Binding Motif Linear Epitopes. Vaccines 2024, 12, 342.

Abstract

Abstract: The worldwide spread of SARS-CoV-2 has led to a significant economic and social burden on a global scale. Even though the pandemic has concluded, there remains apprehension regarding the emergence of highly transmissible variants capable of evading immunity induced by either vaccination or prior infection. The success of viral penetration is the specific amino acid residues of the Receptor Binding Motif (RBM) involved in viral attachment. This region interacts with the cellular receptor ACE2, triggering a neutralizing antibody (nAb) response. In this study, we have evaluated the immunogenicity of serum from individuals who received either a single dose or a combination of different vaccines against the original SARS-CoV-2 strain and mutated linear RBM. Despite a modest antibody response to the wild-type SARS-CoV-2 RBM, the Omicron variants exhibit four mutations in the RBM (S477N, T478K, E484A, F486V) that result in even lower antibody titers. The primary immune responses observed were directed towards IgA and IgG. While nAbs typically target the RBD, our investigation has unveiled a reduced seroreactivity within the RBD's crucial subregion, the RBM. This deficiency may have implications for the generation of protective nAbs. Evaluation of S1WT and S2WT RBM peptides binding to nAbs using microscale thermophoresis revealed a higher affinity (35 nM) for the S2WT sequence (GSTPCNGVEGFNCYF), which includes the FNCY patch. Our findings suggest that the linear RBM of SARS-CoV-2 is not an immunodominant region in vaccinated individuals. Comprehending the intricate dynamics of the humoral response, its interplay with viral evolution, and host genetics is crucial for formulating effective vaccination strategies, not only targeting SARS-CoV-2 but also anticipating potential future 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, Immunology and Microbiology

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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