Detection and quantification of neutralising antibodies against Covid-19 infection

Lead Researchers: Professor Paddy Mallon, Dr Virginie Gautier, UCD Centre for Experimental Pathogen Host Research (CEPHR) and UCD School of Medicine

Funder: Science Foundation Ireland/Enterprise Ireland/IDA Ireland joint Covid-19 Rapid Response Fund

This collaboration between UCD CEPHR and UCD Clinical Research Centre looks at the detection and quantification of neutralising antibodies against Covid-19 infection. As of yet, it is unclear if infection with the SARS-CoV-2 virus confers post-infectious immunity, so determining if it does will open opportunities in both treatment and prevention that could have global impact.

Problem solving

Lack of effective treatment for Covid-19 infection remains a significant limitation in the fight against this global pandemic.

Current treatment options revolve around direct antiviral agents despite the fact that most severe infections arise secondary to abnormal host immune responses driving a cytokine storm that leads to respiratory failure. In the past decade, clinical medicine has been revolutionised by the development of disease-specific immunotherapies using monoclonal antibodies. Although convalescent serum has been used in some preliminary studies in the treatment of Covid-19 infection, its widespread use is limited by lack of availability. Understanding the host immune response is key to unlocking therapeutic opportunities in Covid-19 infection.

Secondly, it is uncertain if infection confers protection against reinfection. Even with recovery after infection, it is uncertain if individuals produce neutralising antibody responses necessary for effective host immunity to prevent against repeated infections. In addition, although vaccines are being developed, whether these produce effective, protective immunity also remains unknown.

At a population level, the prevalence of post-infectious immunity and its effectiveness are unknown, as are the factors that are associated with development of effective host immunity.

To date there is no effective platform to measure post-infectious host immunity against SARS-CoV-2 virus in individuals who have been infected. This limits the effectiveness of the ‘immune passport’ concept whereby protected individuals can access greater freedom of movement.

What will the research project do?

This project addresses data gaps by examining a large, diverse, well phenotyped population of individuals who have recovered from a confirmed Covid-19 infection. Using state of the art technology and biosafety infrastructure the team is developing a platform to examine serum for the presence of neutralising antibodies against live strains of SARS-CoV-2 virus in vitro and to quantify this neutralising effect.

In addition to detecting and quantifying neutralising antibodies, they will purify these antibody fractions and test if they retain viral neutralising capabilities.

This project will enable researchers to characterise the prevalence of post-infectious immunity to Covid-19 and allow them to determine factors associated with development of neutralising antibodies within recovered individuals.

The work will not only hasten development of convalescent serum treatments in Ireland but will drive forward development of neutralising antibodies as specific immune-based therapies for Covid-19 infection. It will also inform the potential for better development of the ‘immune passport’ concept that will help societal recovery from the Covid-19 pandemic.

Research Impact

Quantitative impact:

This work will provide a platform within Ireland to identify individuals with neutralising antibodies necessary to project against Covid-19 reinfection. These individuals can then be approached to donate blood products for use as convalescent serum for the treatment of severe Covid-19 infection. As this treatment is not currently available in Ireland, this work will have an immediate impact at the clinical interface in treatment for severe Covid infection in Ireland.

Furthermore, quantifying protective immunity in individuals is an important concept in the development of ‘immune passports’ and results from this project will contribute to development of meaningful immune passports by providing quantifiable evidence of potential protective immunity.

The project will also provide valuable data on the prevalence of neutralising antibodies in a large representative cohort of individuals in Ireland who have been infected with SARS-CoV-2. This will enable the identification of factors that predict post-infectious immunity and will provide evidence for longevity of neutralising antibodies by examining individuals who are at varying times since recovery from Covid-19 infection.

Qualitative impact:

Ireland has a world-leading biotechnology industry, including in the development and production of immunotherapies. Through this research, we will be taking vital first steps to identify neutralising antibodies that are capable of inhibiting SARS-CoV-2 replication. This can feed into a wider effort, in collaboration with industry partners, to explore the potential for translating these findings into viable immunotherapies that can be produced on a large scale for the treatment of Covid-19 infection.

Project Partners

Professor Alan Landay, Chair of Immunology, Rush Medical Centre
Professor Peter Doran, Director of UCD Clinical Research Centre, UCD School of Medicine
Dr Willard Tinago, Biostatistician, and Mr Alejandro Garcia Leon, Molecular Laboratory Lead, UCD CEPHR and UCD School of Medicine