An investigation into the cross-variant binding and neutralization potentials of patient-derived polyclonal antibodies against SARS-CoV-2 spike protein variants

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Cobley, Simon (2025) An investigation into the cross-variant binding and neutralization potentials of patient-derived polyclonal antibodies against SARS-CoV-2 spike protein variants. MPhil thesis, University of Nottingham.

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Abstract

The novel betacoronavirus SARS-CoV-2 emerged in December 2019 and was responsible for the global COVID-19 pandemic. It caused significant worldwide impact and presented a serious challenge to public health systems. The virus is closely related to other members of the Coronaviridae family, particularly SARS-CoV- 1. SARS-CoV-2 causes a spectrum of disease ranging from asymptomatic or mild respiratory symptoms to severe respiratory illness, systemic infection, and death. The SARS-CoV-2 pandemic highlighted the importance of understanding both the general mechanisms underlying antibody responses to viral infection and the distinct immunological behaviours exhibited by specific viruses.

Successful viral clearance in humans is associated with a robust IgG antibody response. Disease severity and recovery are linked to the development of a neutralising antibody response, particularly targeting the spike glycoprotein. This work aimed to characterise the humoral response to SARS-CoV-2 by analysing antibody binding and neutralisation activity against different spike protein variants, with a focus on how specific antibody profiles influence viral entry inhibition. Using sera from patients admitted to Queen’s Medical Centre Hospital with severe COVID- 19, combined with ELISA and pseudovirus neutralisation assays, we investigated variant-specific IgG responses and assessed neutralising potency across major variants of concern.

We found that many of the patients exhibited varying degrees of antibodydependent enhancement across the three main variants of concern circulating at the time: Alpha, Beta, and Delta. These findings provide insight into how immunity evolves in response to SARS-CoV-2 exposure and vaccination. They contribute to the broader understanding of protective immunity, with implications for vaccine design and public health monitoring of emerging variants.

Item Type: Thesis (University of Nottingham only) (MPhil)
Supervisors: Tarr, Alex
Keywords: SARS-CoV-2, COVID-19 pandemic, IgG antibodies, T cell activation.
Subjects: QS-QZ Preclinical sciences (NLM Classification) > QZ Pathology
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Life Sciences
Item ID: 82666
Depositing User: Cobley, Simon
Date Deposited: 31 Dec 2025 04:40
Last Modified: 31 Dec 2025 04:40
URI: https://eprints.nottingham.ac.uk/id/eprint/82666

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