Retrovirus-based pseudotyped virus neutralisation assays overestimate neutralising activity in sera from participants receiving integrase inhibitors

Scientific Reports, vol. 15, pp. 28580

Abstract

Retroviral pseudotype-based virus neutralisation assays are widely used to estimate functional immunity, but may be unsuitable for testing human immunodeficiency virus (HIV)-infected individuals receiving integrase inhibitor treatment. We evaluated these assays for measuring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and hepatitis C virus (HCV) neutralisation in people living with HIV. SARS-CoV-2 neutralisation was assessed using HIV-based SARS-CoV-2 pseudoviruses in sera from a longitudinal Malawian cohort (n = 1,876), detecting neutralisation across timepoints in 10.5-54.5% of HIV-uninfected vs. 85.5-93.9% of HIV-infected participants (n = 96). HIV-infected sera were re-tested using vesicular stomatitis virus (VSV)-based SARS-CoV-2 pseudoviruses, estimating seroprevalence at 5.6-65.2%, suggesting HIV-based assays overestimate neutralisation. HIV-based VSV-glycoprotein(G) pseudoviruses confirmed non-specific inhibition in 75.0-87.9% of HIV-infected participants. HCV neutralisation was assessed in UK-based HCV patients (n = 100, n = 90 HIV-infected) using murine leukaemia virus (MLV)-based HCV pseudoviruses. Non-HCV-specific inhibition was detected in integrase inhibitor recipients. Median neutralisation of MLV(HCV) pseudoviruses was higher in integrase inhibitor recipients (71.8% vs. 21.3%). Testing HIV(SARS-CoV-2) and MLV(HCV) pseudoviruses against antiretroviral drugs showed interference by integrase inhibitors (specifically, dolutegravir). Isolating IgG from serum removed the interference by residual drugs. Retrovirus-based assays are therefore unsuitable for testing individuals receiving integrase inhibitors. Protective immunity to viruses has likely been over-reported in HIV prevalent populations.

Authors 12

1. Mhairi J. McCormack corresponding

   MRC University of Glasgow Centre for Virus Research · University of Glasgow · Medical Research Council

   Affiliation as printed

   Medical Research Council, University of Glasgow Centre for Virus Research, Glasgow, UK. m.mccormack.1@research.gla.ac.uk

2. Patawee Asamaphan

   MRC University of Glasgow Centre for Virus Research · University of Glasgow · Medical Research Council

   Affiliation as printed

   Medical Research Council, University of Glasgow Centre for Virus Research, Glasgow, UK

3. Ellen C. Hughes

   University of Liverpool · MRC University of Glasgow Centre for Virus Research · University of Glasgow · Medical Research Council

   Affiliation as printed

   Department of Livestock and One Health, Institute of infection, veterinary and ecological sciences, University of Liverpool, Liverpool, UK

   Medical Research Council, University of Glasgow Centre for Virus Research, Glasgow, UK

4. Louis Banda

   Malawi Epidemiology and Intervention Research Unit

   Affiliation as printed

   Malawi Epidemiology and Intervention Research Unit (MEIRU), Lilongwe, Malawi

5. Stephen Kasenda

   Malawi Epidemiology and Intervention Research Unit

   Affiliation as printed

   Malawi Epidemiology and Intervention Research Unit (MEIRU), Lilongwe, Malawi

6. Christopher Davis

   MRC University of Glasgow Centre for Virus Research · University of Glasgow · Medical Research Council

   Affiliation as printed

   Medical Research Council, University of Glasgow Centre for Virus Research, Glasgow, UK

7. Agnieszka M. Szemiel

   MRC University of Glasgow Centre for Virus Research · University of Glasgow · Medical Research Council

   Affiliation as printed

   Medical Research Council, University of Glasgow Centre for Virus Research, Glasgow, UK

8. Amelia Catharine Crampin

   London School of Hygiene & Tropical Medicine · Malawi Epidemiology and Intervention Research Unit · University of Glasgow

   Affiliation as printed

   London School of Hygiene and Tropical Medicine, London, UK

   Malawi Epidemiology and Intervention Research Unit (MEIRU), Lilongwe, Malawi

   School of Health and Wellbeing, University of Glasgow, Glasgow, UK

9. Abena Serwaa Amoah Aachen

   Leiden University Medical Center · London School of Hygiene & Tropical Medicine · Malawi Epidemiology and Intervention Research Unit

   Affiliation as printed

   Leiden University Medical Center, Leiden, Netherlands

   London School of Hygiene and Tropical Medicine, London, UK

   Malawi Epidemiology and Intervention Research Unit (MEIRU), Lilongwe, Malawi

10. Emma C. Thomson

    London School of Hygiene & Tropical Medicine · MRC University of Glasgow Centre for Virus Research · University of Glasgow · Medical Research Council

    Affiliation as printed

    London School of Hygiene and Tropical Medicine, London, UK

    Medical Research Council, University of Glasgow Centre for Virus Research, Glasgow, UK

11. Antonia Ying Wai Ho

    MRC University of Glasgow Centre for Virus Research · University of Glasgow · Medical Research Council

    Affiliation as printed

    Medical Research Council, University of Glasgow Centre for Virus Research, Glasgow, UK

12. Brian J. Willett

    MRC University of Glasgow Centre for Virus Research · University of Glasgow · Medical Research Council

    Affiliation as printed

    Medical Research Council, University of Glasgow Centre for Virus Research, Glasgow, UK