Increased seroprevalence and improved antibody responses following third primary SARS-CoV-2 immunisation: an update from the COV-AD study

This research has not been peer-reviewed. It is a preliminary report that should not be regarded as conclusive, guide clinical practice or health-related behaviour, or be reported in news media as established information.


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.


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


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.


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, overall seroprevalence and antibody levels remained significantly lower than healthy controls. No differences in serological responses were observed between individuals who received the 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 responses following their third vaccine dose (61.5% vs 11.1%).


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

Author list

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, Smita Y. Patel, Sinisa Savic, Alex G. Richter, Siobhan O. Burns, COVAD Consortium

Novel Coronavirus SARS-CoV-2


Research Square