AUTHOR=Shields Adrian M. , Faustini Sian E. , Hill Harriet J. , Al-Taei Saly , Tanner Chloe , Ashford Fiona , Workman Sarita , Moreira Fernando , Verma Nisha , Wagg Hollie , Heritage Gail , Campton Naomi , Stamataki Zania , Drayson Mark T. , Klenerman Paul , Thaventhiran James E. D. , Elkhalifa Shuayb , Goddard Sarah , Johnston Sarah , Huissoon Aarnoud , Bethune Claire , Elcombe Suzanne , Lowe David M. , Patel Smita Y. , Savic Sinisa , Richter Alex G. , Burns Siobhan O. , the COV-AD consortium , Ahmed Zahra , Best Angus , Dasgin Joanne , Dinally Mohammad , Efstathiou Elena , McCarthy Theresa , Hoque Madeeha , Page Shannon , Plant Timothy , Suleiman Zehra , Townsend Neil , Trinham Charlotte , Walder Sinead , Bancroft Hollie , Bates Michelle , Clifford Hayley , McGee Christopher , Chee Samuel , Common Lucy , Herwadkar Archana , Knowles Karen , Poulaka Maria , Davis Georgina , Mullan Daniel , Wareham Stuart , Dhalla Fatima , Jain Rashmi , Morsi Hadeil , Peters Nicholas , Gompels Mark , Slowinsksa Malgorzata , Hartland Dan , Heritage Emily , Humphreys Joe , Hughes Deborah , Ivory Ann , Kelly Sinead , O’Grady Eileen , Shajidevadas Archana TITLE=Increased Seroprevalence and Improved Antibody Responses Following Third Primary SARS-CoV-2 Immunisation: An Update From the COV-AD Study JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.912571 DOI=10.3389/fimmu.2022.912571 ISSN=1664-3224 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.