B3869 - Development of standardised virus pseudotype assay to quantify SARS-CoV-2 neutralising antibodies in saliva and serum - 21/09/2021

B number: 
B3869
Principal applicant name: 
Ore Francis | University of Bristol (United Kingdom)
Co-applicants: 
Title of project: 
Development of standardised virus pseudotype assay to quantify SARS-CoV-2 neutralising antibodies in saliva and serum
Proposal summary: 

SARS-CoV-2 neutralising antibody (nAb) correlates with protection against SARS-CoV-2 infection and COVID-19, and measuring nAbs is crucial for COVID-19 patient management, vaccine trials and mechanistic research. I have developed a VPNA to measure nAbs, that does not require the high biosafety levels or time-consuming protocols necessary for using live SARS-CoV-2. This assay correlates with assays that measure abundance and live SARS-CoV-2 neutralisation ability of S-protein specific antibodies from sera. However, initial SARS-CoV-2-cell entry and subsequent shedding occurs in the upper-respiratory tract, so it is important to characterise immune responses in mucosae and blood. I plan to develop the anti-S-protein VPNA for saliva samples and standardise serum and saliva VPNAs to WHO reference samples. This updated VPNA will be used to characterise mucosal and systemic nAb responses in individuals who have had a natural SARS-CoV-2 infection with a focus on infection within families and to assess the efficacy of vaccination protocols.

Impact of research: 
A robust, high-throughput VPNA, optimised for serum and saliva samples and scaled to international standards is not yet available. The University of Bristol has identified patient samples from individuals before and after SARS-CoV-2 emergence and samples from patients undergoing different vaccination regimens. Characterisation of humoral immune responses, particularly nAbs, from the ALSPAC cohort will reveal local transmission dynamics in a detail not yet available. This work may reveal whether mucosal or systemic nAbs correlate best with differences observed in SARS-CoV-2 infection across demographics such as regional location or profession, metrics that may inform future pandemic-mediated policy (i.e., lockdowns). Additionally, samples from vaccinated individuals will reveal patterns corresponding to dose and timing of available vaccines. This could be vital in optimising current vaccination/booster policy. Additionally, VPNAs based on emerging VOCs will determine efficacy of current vaccines against new VOCs.
Date proposal received: 
Friday, 3 September, 2021
Date proposal approved: 
Monday, 13 September, 2021
Keywords: 
Immunology, COVID-19, Cell culture, Viral assay, Biological samples -e.g. blood, cell lines, saliva, etc., Immunity, SARS-CoV-2 COVID-19 Antibody