SARS-CoV-2 Vaccine Responses in Individuals with Antibody Deficiency: Findings from the COV-AD Study

Shields, Adrian; Faustini, Sian; Hill, Harriet J.; Al-Taei, Saly; Tanner, Chloe; Ashford, Fiona; Workman, Sarita; Moreira, Fernando; Verma, Nisha; Wagg, Hollie; Heritage, Gail; Campton, Naomi; Stamataki, Zania; Klenerman, Paul; Thaventhiran, James; Goddard, Sarah; Johnston, Sarah; Huissoon, Aarnoud; Bethune, Claire; Elcombe, Suzanne; Lowe, David M.; Patel, Smita Y.; Savic, Sinisa; Burns, Siobhan O.; Richter, Alex; Ahmed, Zahra; Bancroft, Hollie; Bates, Michelle; Clifford, Hayley; Davis, Glyn; Dasgin, Joanne; Dinally, Mohammad; Dhalla, Fatima; Efstathiou, Elena; Elkhalifa, Shuayb; Gompels, Mark; Hartland, Dan; Hoque, Madeeha; Heritage, Emily; Hughes, David A.; Ivory, Ann; Jain, Rashmi; Kelly, Sinéad; McCarthy, Theresa; McGee, Christopher; Mullan, Daniel; Morsi, Hadeil; O'Grady, Eileen; Page, Shannon; Peters, Nicholas S.; Plant, Timothy; Shajidevadas, Archana; Slowinsksa, Malgorzata; Suleiman, Z; Townsend, Neil; Trinham, Charlotte; Wareham, Stuart; Walder, S

doi:10.1007/s10875-022-01231-7

Cited by 48 publications

(80 citation statements)

References 28 publications

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“…Recruitment to the COV-AD study has been described elsewhere ( 5 ). Briefly, from March 2021, patients with primary or secondary antibody deficiency were recruited from Immunology centres across the United Kingdom.…”

Section: Methodsmentioning

confidence: 99%

“…A detailed account of the methods used for serological and cellular studies is available elsewhere ( 5 ). Briefly, serum or dried blood samples were tested for the presence of total anti-spike glycoprotein antibodies (The Binding Site, Birmingham, UK).…”

Section: Methodsmentioning

confidence: 99%

“…Serological results are presented as the percentage of participants who are seropositive and the median of the IgGAM ratio in seropositive participants. IgG serological responses directed against the Wuhan spike protein and the B.1.1.529 (Omicron) SARS-CoV-2 variant of concern were measured using an in-house ELISA as previously described; target proteins were sourced from SinoBiological as previously described ( 5 ). Live virus neutralisation assays were performed using Vero cells on paired serum samples before and after vaccination at a 1/50 serum dilution as previously described ( 5 ).…”

Section: Methodsmentioning

confidence: 99%

“…The immunogenicity and efficacy of the initial two-dose SARS-CoV-2 vaccination schedule and booster immunisations have been comprehensively studied in healthy adults ( 1 – 4 ). Compared to healthy individuals, the immunogenicity of two doses of the AstraZeneca ChAdOx1 nCoV-19 and Pfizer BioNTech 162b2 SARS-CoV-2 vaccines are significantly diminished in individuals with primary (PID) and secondary immunodeficiencies (SID) ( 5 ). The COVID-19 in patients with antibody deficiency (COV-AD) study has previously shown that the seroprevalence of anti-SARS-CoV-2 antibodies is 54.8% following two vaccine doses, with seroprevalence being higher in recipients of the Pfizer vaccine, compared to the AstraZeneca ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

“…Compared to healthy individuals, the immunogenicity of two doses of the AstraZeneca ChAdOx1 nCoV-19 and Pfizer BioNTech 162b2 SARS-CoV-2 vaccines are significantly diminished in individuals with primary (PID) and secondary immunodeficiencies (SID) ( 5 ). The COVID-19 in patients with antibody deficiency (COV-AD) study has previously shown that the seroprevalence of anti-SARS-CoV-2 antibodies is 54.8% following two vaccine doses, with seroprevalence being higher in recipients of the Pfizer vaccine, compared to the AstraZeneca ( 5 ). Other studies have estimated post-vaccine seroprevalence to lie between 20% and 80% in patients with inborn errors of immunity ( 6 – 10 ).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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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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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

et al. 2022

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Clinical and laboratory characteristics of patients with symptomatic secondary immunodeficiency following the treatment of haematological malignancies

Shields

Faustini

Young

et al. 2023

eJHaem

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Secondary immunodeficiency (SID), manifesting as increased susceptibility to infection, is an emergent clinical problem in haematoncology. Management of SID includes vaccination, prophylactic antibiotics (pAbx) and immunoglobulin replacement therapy (IgRT). We report clinical and laboratory parameters of 75 individuals, treated for haematological malignancy, who were referred for immunological assessment due to recurrent infections. Forty‐five were managed with pAbx while thirty required IgRT after failing to improve on pAbx. Individuals requiring IgRT had significantly more bacterial, viral and fungal infections resulting in hospitalization at least 5 years after their original haemato‐oncological diagnosis. Following immunological assessment and intervention, a 4.39‐fold reduction in the frequency of hospital admissions to treat infection was observed in the IgRT cohort and a 2.30‐fold reduction in the pAbx cohort. Significant reductions in outpatient antibiotic use were also observed in both cohorts following immunology input. Patients requiring IgRT were more hypogammaglobulinaemic and had lower titres of pathogen‐specific antibodies and smaller memory B cell populations than those requiring pAbx. Test vaccination with pneumococcal conjugate vaccine discriminated poorly between the two groups. Patients requiring IgRT could be distinguished by combining wider pathogen‐specific serology with a frequency of hospital admissions for infection. If validated in larger cohorts, this approach may circumvent the need for test vaccination and enhance patient selection for IgRT.

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Clinical efficacy of SARS‐CoV‐2 Omicron‐neutralizing antibodies in immunoglobulin preparations for the treatment of agammaglobulinemia in patients with primary antibody deficiency

Karbiener,

Kindle,

Meyts

et al. 2024

Journal of Medical Virology

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Immunocompromised individuals are at significantly elevated risk for severe courses of coronavirus disease 2019 (COVID‐19). In addition to vaccination, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) neutralizing antibodies (nAbs) have been applied throughout the pandemic, with time of treatment onset and potency against the currently prevailing virus variant identified as relevant factors for medical benefit. Using data from the European Society for Immunodeficiencies (ESID) registry, the present study evaluated COVID‐19 cases in three groups of patients with inborn errors of immunity (IEI; 981 agammaglobulinemia patients on immunoglobulin replacement therapy (IGRT); 8960 non‐agammaglobulinemia patients on IGRT; 14 428 patients without IGRT), and the neutralizing capacity of 1100 immunoglobulin lots against SARS‐CoV‐2 (“Wuhan” and Omicron strains), throughout 3 years. From the first (2020/2021) to the second (2021/2022) cold season, i.e., during the virus drift to the more contagious Omicron variants, an increase in case numbers was recorded that was comparable (~2‐ to 3‐fold) for all three study groups. During the same period, immunoglobulin lots showed a profound nAb increase against the archetypal SARS‐CoV‐2 strain, yet only low levels of Omicron nAbs. Notably, shortly before the third (2022/2023) cold season, Omicron‐neutralizing capacity of released immunoglobulin lots had plateaued at high levels. From the second to the third cold season, COVID‐19 cases dropped markedly. While a ~6‐fold case reduction was recorded for the groups of non‐agammaglobulinemia patients on IGRT and IEI patients not receiving IGRT, the decline was ~30‐fold for the group of agammaglobulinemia patients on IGRT. These findings suggest a substantial COVID‐19‐protective effect of IGRT, at least for distinct groups of antibody‐deficient patients.

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SARS-CoV-2 Vaccine Responses in Individuals with Antibody Deficiency: Findings from the COV-AD Study

Cited by 48 publications

References 28 publications

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

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

Clinical and laboratory characteristics of patients with symptomatic secondary immunodeficiency following the treatment of haematological malignancies

Clinical efficacy of SARS‐CoV‐2 Omicron‐neutralizing antibodies in immunoglobulin preparations for the treatment of agammaglobulinemia in patients with primary antibody deficiency

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