MRC-University of Glasgow Centre for Virus Research

Viral Immunology

Our laboratory is situated in the Henry Wellcome Building at the MRC-University of Glasgow Centre for Virus Research (CVR). Our main interests are the ways in which viruses cause disease; the immune response to infection; and the development of viral vaccines.

Our work focuses on viruses of importance to human and veterinary medicine, including coronaviruses, morbilliviruses, caliciviruses, bunyaviruses, lentiviruses, rhabdoviruses and parvoviruses. Active research projects are investigating:

• cross-neutralisation of SARS-CoV-2 variants
• determinants of SARS-CoV-2 virulence, evasion of immunity and vaccine effectiveness
• correlates of immunity to circulating measles virus genotypes
• cross-species transmission and antibody-mediated neutralisation of morbilliviruses
• SARS-CoV-2 spread in the UK domestic cat population
• Drivers of bunyavirus emergence in pastoral and agropastoral communities in Africa

Immunity to SARS-CoV-2

In early 2020, we initiated a program of research aimed at investigating the antibody response to infection with SARS-CoV-2, with a view to tracking the spread of the virus throughout the community and assessing the level of immunity elicited by infection. By combining in-house ELISA assays with pseudotype-based neutralisation assays, we were able to track the spread of SARS-CoV-2 across NHS Greater Glasgow and Clyde, the largest health board in Scotland (Hughes et al. 2021). We showed that males, 45-64-years olds, and patients in secondary care were most likely to be seropositive. Further, we established that approximately half of seropositive individuals (assessed by ELISA) developed neutralising antibodies (Hughes et al. 2021).

Building on these studies, we examined evasion of the neutralising response by the Beta and Delta variants of SARS-CoV-2 (Davies et al. 2021), and the effect of antigenic variation on evasion of the immune response elicited by vaccination with either ChAdOx1 (AstraZeneca) or BNT162b2 (Pfizer) vaccines. The emergence of the Omicron lineage of viruses at the end of 2021 signalled a new phase in the evolution of SARS-CoV-2.

Working closely with colleagues across the University of Glasgow and the wider UK academic and healthcare communities, we established that the Omicron variant had a phenotype that had changed fundamentally compared with all prior variants (Research briefing). The Omicron variants displayed reduced neutralisation by antibodies elicited by vaccination, while T cell responses were relatively preserved (Willett et al. 2022). Further, real-world vaccine effectiveness was partially restored by booster vaccination. Our study revealed that Omicron displayed distinct entry and fusion properties to preceding variants, entering cells via a TMPRSS2-independent, endosomal entry pathway (Willett et al. 2022). This fundamental change in the viral entry mechanism was not predicted by sequencing data; rather it was revealed by observations in cell culture experiments from several laboratories, including those at the CVR. This project was supported in part by HDR-UK, further details are available here.

One of our primary SARS-CoV-2 research objectives is to elucidate the nature of the virus-host interaction;  investigating the strength, specificity and duration of humoral immunity. Working closely with colleagues at the University of Birmingham, we are currently investigating vaccine effectiveness in at-risk populations; including children (Dowell et al, 2022a & Dowell et al., 2022b), the elderly and patients with chronic lymphocytic leukemia (Parry et al, 2022a & Parry et al, 2022b). These studies will inform future vaccine strategies for preventing SARS-CoV-2 infection and the development of COVID-19.

Emerging morbilliviruses of wildlife and humans

The global spread of peste des petits ruminants virus (PPRV)

In May 2011, the General Session of the Office International des Epizooties declared the world to be free from rinderpest virus, the causative agent of “cattle plague”. Rinderpest virus (RPV) is a morbillivirus, a close relative of measles virus (MeV). Like rinderpest virus, measles virus is now being considered for global eradication by vaccination. However, there is increasing concern that if such a vaccination programme was to be successful, the requirement for vaccination would cease. As a result, humans would no longer have cross-protection against zoonotic infections with closely-related animal morbilliviruses. Significant concerns have now been raised about the threat from the carnivore morbillivirus, canine distemper virus (CDV), a virus capable of infecting diverse species including dogs, ferrets, martens, lions, hyenas and seals. This ability to cross species renders CDV a significant threat to many endangered species of wildlife. Moreover, pathogenic CDV infections have been described in primates, raising the possibility of zoonotic transmissions to humans. There is now intense interest in the viral reservoirs of CDV and the degree of cross-protection conferred by MV vaccination as a means of guarding against cross-species transmission.

Neutralisation of morbilliviruses by antibodies is currently measured using a restricted subset of live viruses that grow readily in culture. Thus it is not possible to compare antibody responses to vaccine viruses with those against primary field strains of virus, making predictions of vaccine efficacy and likelihood of zoonotic transmission challenging. We have developed novel viral pseudotype-based assay systems with which serological responses to diverse animal morbilliviruses can be measured rapidly, with high sensitivity and specificity (see Logan et al. 2016a & Logan et al., 2016b). Using this simple methodology, we are measuring neutralizing antibody responses against primary field strains of virus, novel emerging morbilliviruses, and unique biotypes and serotypes of virus for which assays are currently unavailable. We have developed parallel systems for diverse morbilliviruses; viral pseudotypes based on peste des petits ruminants (PPRV), CDV, RPV, MeV and phocine distemper virus (PDV), and target cell lines expressing the cognate receptors for each virus.

This project brings a comprehensive understanding of the spread of morbilliviruses in livestock (Herzog et al., 2019; 2020a & 2020b) and wildlife species (Gilbert et al., 2020). It addresses whether morbilliviruses are being maintained in atypical host species and whether these species are a source of infection for susceptible hosts. It provides epidemiological and biological data to inform future strategies for virus eradication by vaccination, illuminating the extent of virus spread and the likely species that will require to be vaccinated. The high-throughput assay techniques we employ build capacity in the UK for "rapid response" to emerging viral diseases.

Listen to Prof. Willett discussing morbillivirus research at the CVR here: CVR Podcast

Group members

Diagnostic tools