Neutralising antibody responses in acute hepatitis C and SARS-CoV-2 infection

Neutralising antibodies (nAbs) are capable of blocking viral entry to host cells. Understanding the nAb response in early infection informs preventative and therapeutic interventions. The acute phase of hepatitis C virus (HCV) infection is characterised by two bottlenecks of viral diversity, one at the initiation of infection (selection of transmitted/founder (T/F) variants), and another within 100 days of infection (emergence of fit variants against host immunity). Three out of four patients with HCV develop chronic infection which is associated with a delayed nAb response against variants emerging from the second bottleneck. However, the ability for HCV T/F variants to induce nAbs is poorly understood. This first part of this thesis aimed to characterise T/Fs using next-generation sequencing, and determine if the immunogenicity of T/Fs was associated with infection outcome. Approximately one in four primary HCV infections were found to originate from a single T/F virus and in those with spontaneous clearance of infection, T/Fs have a stronger binding affinity towards cluster of differentiation (CD) -81, a key receptor for HCV cell entry. T/Fs of spontaneous clearers were also more susceptible to neutralisation compared to chronic progressors. The second part of this thesis describes how the techniques utilised to study nAb responses in HCV were adapted to study Severe acute respiratory syndrome (SARS) coronavirus (CoV) -2, hoping to unravel the comparable nAb protection in coronavirus disease 2019 (COVID-19) infection. A new assay to study SARS-CoV-2 neutralisation was optimised and used to characterise the longitudinal nAb responses in individuals recovering from COVID-19 infection, and up to six months post-infection. In the majority, nAb responses (titers and neutralisation capacity) were evident, but declined modestly, with most being above background at six months post-infection. This decline was associated with older age, but not with gender or illness severity. In summary, this thesis examined the role of viral and nAb traits associated with two different viruses and their varied infection outcomes. The findings contribute to better understanding of interactions between virus and host antibody responses, which is critical for vaccine design.

Grantor dc:publisher

UNSW, Sydney

Year dc:date

2021

Author dc:creator

• Abayasingam, Arunasingam ; https://orcid.org/0000-0002-9406-3058

• Hepatitis C virus
• COVID-19
• Neutralising antibodies
• Transmitted/founder
• Pseudoparticles
• Neutralisation assay

Statement dc:rights

• open access
• CC BY 4.0
• free_to_read

Licence

• https://purl.org/coar/access_right/c_abf2
• https://creativecommons.org/licenses/by/4.0/

Language dc:language

en

Identifier

https://doi.org/10.26190/unsworks/24487

OAI identifier oai:identifier

oai:unsworks.library.unsw.edu.au:1959.4/100780