Frontiers in Immunology (Jun 2022)

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

  • Adrian M. Shields,
  • 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 Johnston,
  • Aarnoud Huissoon,
  • Claire Bethune,
  • Suzanne Elcombe,
  • David M. Lowe,
  • David M. Lowe,
  • Smita Y. Patel,
  • Smita Y. Patel,
  • Sinisa Savic,
  • Alex G. Richter,
  • Alex G. Richter,
  • Siobhan O. Burns,
  • Siobhan O. Burns,
  • the COV-AD consortium,
  • Zahra Ahmed,
  • Angus Best,
  • Joanne Dasgin,
  • Mohammad Dinally,
  • Elena Efstathiou,
  • Theresa McCarthy,
  • Madeeha Hoque,
  • Shannon Page,
  • Timothy Plant,
  • Zehra Suleiman,
  • Neil Townsend,
  • Charlotte Trinham,
  • Sinead Walder,
  • Hollie Bancroft,
  • Michelle Bates,
  • Hayley Clifford,
  • Christopher McGee,
  • Samuel Chee,
  • Lucy Common,
  • Archana Herwadkar,
  • Karen Knowles,
  • Maria Poulaka,
  • Georgina Davis,
  • Daniel Mullan,
  • Stuart Wareham,
  • Fatima Dhalla,
  • Rashmi Jain,
  • Hadeil Morsi,
  • Nicholas Peters,
  • Mark Gompels,
  • Malgorzata Slowinsksa,
  • Dan Hartland,
  • Emily Heritage,
  • Joe Humphreys,
  • Deborah Hughes,
  • Ann Ivory,
  • Sinead Kelly,
  • Eileen O’Grady,
  • Archana Shajidevadas

DOI
https://doi.org/10.3389/fimmu.2022.912571
Journal volume & issue
Vol. 13

Abstract

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BackgroundPatients 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.ObjectivesTo determine the immunogenicity of the third primary SARS-CoV-2 immunisation in a heterogeneous cohort of patients with antibody deficiency.MethodsParticipants 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.ResultsFollowing 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%).ConclusionThese data support the widespread use of third primary immunisations to enhance humoral immunity against SARS-CoV-2 in individuals with antibody deficiency.

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