Booster Vaccination Against SARS-CoV-2 Induces Potent Immune Responses in People With Human Immunodeficiency Virus

Author:

Fidler Sarah123,Fox Julie45,Tipoe Timothy6,Longet Stephanie7,Tipton Tom7,Abeywickrema Movin5,Adele Sandra6,Alagaratnam Jasmini12,Ali Mohammad6,Aley Parvinder K8,Aslam Suhail5,Balasubramanian Anbhu5,Bara Anna3,Bawa Tanveer5,Brown Anthony6,Brown Helen6,Cappuccini Federica9,Davies Sophie9,Fowler Jamie9,Godfrey Leila9,Goodman Anna L510,Hilario Kathrine5,Hackstein Carl-Philipp6,Mathew Moncy5,Mujadidi Yama F9,Packham Alice5,Petersen Claire12,Plested Emma9,Pollock Katrina M3,Ramasamy Maheshi N811,Robinson Hannah8,Robinson Nicola612,Rongkard Patpong6,Sanders Helen9,Serafimova Teona5,Spence Niamh5,Waters Anele5,Woods Danielle9,Zacharopoulou Panagiota6,Barnes Eleanor621112,Dunachie Susanna6111314,Goulder Philip61115,Klenerman Paul61112,Winston Alan12,Hill Adrian V S9,Gilbert Sarah C9,Carroll Miles716,Pollard Andrew J912,Lambe Teresa8917,Ogbe Ane6,Frater John61112ORCID

Affiliation:

1. Department of Infectious Disease, Faculty of Medicine, Imperial College London , London , United Kingdom

2. Department of HIV Medicine, St Mary's Hospital, Imperial College Healthcare National Health Service (NHS) Trust , London , United Kingdom

3. National Institute for Health and Care Research (NIHR) Imperial Clinical Research Facility and NIHR Imperial Biomedical Research Centre , London , United Kingdom

4. NIHR Guy's and St Thomas’ Biomedical Research Centre , London , United Kingdom

5. Department of Infection, Harrison Wing and NIHR Clinical Research Facility, Guys and St Thomas’ NHS Trust , London , United Kingdom

6. Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford , Oxford , United Kingdom

7. Nuffield Department of Medicine, Wellcome Centre for Human Genetics, University of Oxford , Oxford , United Kingdom

8. Oxford Vaccine Group, Department of Pediatrics, University of Oxford , Oxford , United Kingdom

9. Nuffield Department of Medicine, The Jenner Institute, University of Oxford , Oxford , United Kingdom

10. Medical Research Council Clinical Trials Unit, University College London , London , United Kingdom

11. Oxford University Hospitals NHS Foundation Trust , Oxford , United Kingdom

12. NIHR Oxford Biomedical Research Centre , Oxford , United Kingdom

13. Nuffield Department of Medicine, Centre for Tropical Medicine and Global Health, University of Oxford , Oxford , United Kingdom

14. Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University , Bangkok , Thailand

15. Department of Paediatrics, University of Oxford , Oxford , United Kingdom

16. Public Health England , Porton Down, Salisbury , United Kingdom

17. Chinese Academy of Medical Sciences Oxford Institute , Oxford , United Kingdom

Abstract

Abstract Background People with human immunodeficiency virus (HIV) on antiretroviral therapy (ART) with good CD4 T-cell counts make effective immune responses following vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There are few data on longer term responses and the impact of a booster dose. Methods Adults with HIV were enrolled into a single arm open label study. Two doses of ChAdOx1 nCoV-19 were followed 12 months later by a third heterologous vaccine dose. Participants had undetectable viraemia on ART and CD4 counts >350 cells/µL. Immune responses to the ancestral strain and variants of concern were measured by anti-spike immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA), MesoScale Discovery (MSD) anti-spike platform, ACE-2 inhibition, activation induced marker (AIM) assay, and T-cell proliferation. Findings In total, 54 participants received 2 doses of ChAdOx1 nCoV-19. 43 received a third dose (42 with BNT162b2; 1 with mRNA-1273) 1 year after the first dose. After the third dose, total anti-SARS-CoV-2 spike IgG titers (MSD), ACE-2 inhibition, and IgG ELISA results were significantly higher compared to Day 182 titers (P < .0001 for all 3). SARS-CoV-2 specific CD4+ T-cell responses measured by AIM against SARS-CoV-2 S1 and S2 peptide pools were significantly increased after a third vaccine compared to 6 months after a first dose, with significant increases in proliferative CD4+ and CD8+ T-cell responses to SARS-CoV-2 S1 and S2 after boosting. Responses to Alpha, Beta, Gamma, and Delta variants were boosted, although to a lesser extent for Omicron. Conclusions In PWH receiving a third vaccine dose, there were significant increases in B- and T-cell immunity, including to known variants of concern (VOCs).

Funder

UK Research and Innovation

Engineering and Physical Sciences Research Council

National Institutes for Health Research

Thames Valley and South Midlands NIHR Clinical Research Network

AstraZeneca

Wellcome Trust

NIHR Global Research Professorship

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Microbiology (medical)

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