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. 2022 Jun 2:13:912571.
doi: 10.3389/fimmu.2022.912571. eCollection 2022.

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

Adrian M Shields  1   2 , Sian E Faustini  1 , Harriet J Hill  3 , Saly Al-Taei  1 , Chloe Tanner  1 , Fiona Ashford  1 , Sarita Workman  4 , Fernando Moreira  4 , Nisha Verma  4 , Hollie Wagg  5 , Gail Heritage  5 , Naomi Campton  5 , Zania Stamataki  3 , Mark T Drayson  1 , Paul Klenerman  6 , James E D Thaventhiran  7 , Shuayb Elkhalifa  8 , Sarah Goddard  9 , Sarah Johnston  10 , Aarnoud Huissoon  2 , Claire Bethune  11 , Suzanne Elcombe  12 , David M Lowe  4   13 , Smita Y Patel  6   14 , Sinisa Savic  15 , Alex G Richter  1   2 , Siobhan O Burns  4   13 ; COV-AD consortium
Collaborators, Affiliations

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

Adrian M Shields et al. Front Immunol. .

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.

Keywords: COVID-19; CVID; SARS-CoV-2; inborn errors of immunity; primary immunodeficiency; secondary immunodeficiency; vaccination.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Serological response to third primary immunisation in COV-AD participants: (A) Total anti-SARS-CoV-2 spike glycoprotein antibodies in all participants sampled throughout the COV-AD study presented by time of sampling relative to V2 and V3. (B) Comparison of total anti-SARS-CoV-2 spike serological responses of infection naive COV-AD participants and healthy controls 1-2 months post second vaccine dose (Post V2), up to 1 month prior to third vaccine dose (Pre V3) and 1-2 months post third vaccine dose (Post V3). (C) Comparison of total anti-SARS-CoV-2 spike serological responses of infection naive COV-AD participants 1-2 months post third vaccine dose by initial two-dose vaccine received. (D) Comparison of total anti-spike serological responses of COV-AD participants 1-2 months post third vaccine dose by prior infection status. (E) Comparison of total anti-spike serological responses of infection naive COV-AD participants 1-2 most post third vaccine dose by underlying immunodeficiency. (F) Comparison of total anti-spike antibody levels of paired samples taken 1-2 months after the second vaccine dose and 1-2 months after the third vaccine dose. (G) Comparison of IgG binding to the original Wuhan SARS-CoV-2 spike glycoprotein between paired samples taken before and after third primary immunisation. (H) Comparison of IgG binding to the B.1.1.529 (Omicron) SARS-CoV-2 spike glycoprotein between paired samples taken before and after third primary immunisation. (I) Neutralisation capacity of paired serum samples taken before and after third vaccine dose against SARS-CoV-2 in a live virus neutralisation assay. In all cases, the grey shaded area represents the assay cutoff.
Figure 2
Figure 2
T cell response to third primary immunisation in COV-AD participants: (A) Longitudinal comparison of T cell responses measured using the T-SPOT®.COVID assay in COV-AD participants by prior infection status. (B) Longitudinal comparison of T cell responses measured using an interferon-gamma release assay in COV-AD participants by initial two-dose vaccine schedule received. Data points represented by stars are individuals with evidence of prior infection. In both cases, the grey shaded area represents the assay cutoff. (C) Comparison of IgGAM ratios of individuals with detectable and undetectable T cell responses.
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