Increased Seroprevalence and Improved Antibody Responses Following Third Primary SARS-CoV-2 Immunisation: An Update From the COV-AD Study

COV-AD consortium, Adrian M Shields*, Sian E Faustini, Harriet J Hill, Saly Al-Taei, Chloe Tanner, Fiona Ashford, Sarita Workman, Fernando Moreira, Nisha Verma, Hollie Wagg, Gail Heritage, Naomi Campton, Zania Stamataki, Mark T Drayson, Paul Klenerman, James E D Thaventhiran, Shuayb Elkhalifa, Sarah Goddard, Sarah JohnstonAarnoud Huissoon, Claire Bethune, Suzanne Elcombe, David M Lowe, Smita Y Patel, Sinisa Savic, Alex G Richter*, Siobhan O Burns*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

Background: Patients with primary and secondary antibody deficiency are vulnerable to COVID-19 and demonstrate diminished responses following two-dose SARS-CoV-2 vaccine schedules. Third primary vaccinations have been deployed to enhance their humoral and cellular immunity.

Objectives: To determine the immunogenicity of the third primary SARS-CoV-2 immunisation in a heterogeneous cohort of patients with antibody deficiency.

Methods: Participants enrolled in the COV-AD study were sampled before and after their third vaccine dose. Serological and cellular responses were determined using ELISA, live-virus neutralisation and ELISPOT assays.

Results: Following a two-dose schedule, 100% of healthy controls mounted a serological response to SARS-CoV-2 vaccination, however, 38.6% of individuals with antibody deficiency remained seronegative. A third primary SARS-CoV-2 vaccine significantly increased anti-spike glycoprotein antibody seroprevalence from 61.4% to 76.0%, the magnitude of the antibody response, its neutralising capacity and induced seroconversion in individuals who were seronegative after two vaccine doses. Vaccine-induced serological responses were broadly cross-reactive against the SARS-CoV-2 B.1.1.529 variant of concern, however, seroprevalence and antibody levels remained significantly lower than healthy controls. No differences in serological responses were observed between individuals who received AstraZeneca ChAdOx1 nCoV-19 and Pfizer BioNTech 162b2 during their initial two-dose vaccine schedule. SARS-CoV-2 infection-naive participants who had received a heterologous vaccine as a third dose were significantly more likely to have a detectable T cell response following their third vaccine dose (61.5% vs 11.1%).

Conclusion: These data support the widespread use of third primary immunisations to enhance humoral immunity against SARS-CoV-2 in individuals with antibody deficiency.

Original languageEnglish
Article number912571
Number of pages9
JournalFrontiers in immunology
Volume13
DOIs
Publication statusPublished - 2 Jun 2022

Bibliographical note

Copyright © 2022 Shields, Faustini, Hill, Al-Taei, Tanner, Ashford, Workman, Moreira, Verma, Wagg, Heritage, Campton, Stamataki, Drayson, Klenerman, Thaventhiran, Elkhalifa, Goddard, Johnston, Huissoon, Bethune, Elcombe, Lowe, Patel, Savic, Richter, Burns and the COV-AD consortium.

Keywords

  • Antibodies, Viral
  • Antibody Formation
  • COVID-19
  • COVID-19 Vaccines
  • ChAdOx1 nCoV-19
  • Humans
  • SARS-CoV-2
  • Seroepidemiologic Studies
  • Vaccination
  • Viral Vaccines
  • secondary immunodeficiency
  • CVID
  • primary immunodeficiency
  • inborn errors of immunity
  • vaccination

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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