COVID-19 vaccines appear less effective among patients with antibody deficiencies
Patients with antibody deficiencies demonstrated reduced immunogenicity following vaccination against the SARS-CoV-2 virus, according to a study published in Journal of Clinical Immunology.
These findings demonstrate the ongoing risk that the virus presents these patients, Adrian M. Shields, MBBS, MRCP, PhD, clinical lecturer at University of Birmingham Institute of Immunology and Immunotherapy in the United Kingdom, and colleagues wrote.
The COVID-19 in patients with antibody deficiency (COV-AD) study began recruiting 320 patients (median age, 58.5 years; 40% men) aged 18 years and older from eight immunology centers in the United Kingdom in March 2021.
These patients, who had been on immunoglobulin therapy or who had an IgG of less than 4 g/L and were receiving antibiotic prophylaxis, also received two doses of the AstraZeneca or Pfizer-BioNTech vaccine.
The researchers studied a cohort of 205 healthy control participants (median age, 44 years; 28% men) from the COVID-19 convalescent study at University Hospitals Birmingham NHS Foundation Trust who had two doses of the Pfizer-BioNTech vaccine as well.
The seropositivity of the patients with antibody deficiencies was 54.8%, compared with 100% among the control patients. Specifically, seropositivity was 52.1% for patients with common variable immunodeficiency and 55.8% for patients with secondary immunodeficiency arising from hematological cause.
Also, 65.7% of the patients with antibody deficiency receiving the Pfizer-BioNTech vaccine were seropositive, compared with 48% of the patients who received the AstraZeneca vaccine (P = .03). The patients receiving the Pfizer-BioNTech vaccine had an IgGAM ratio of 3.73 while the AstraZeneca recipients had an IgGAM ratio of 2.39 (P = .0003).
Less than 10% of patients with primary or secondary antibody deficiencies had a neutralizing antibody response that was equivalent to the response among healthy control patients after two doses of a SARS-CoV-2 vaccine.
Further, patients who demonstrated a vaccine response had significantly reduced anti-spike IgG binding against the SARS-CoV-2 delta and omicron variants.
According to the researchers, these results indicate that most patients with antibody deficiencies have inadequate vaccine-induced antibody responses, prompting the need for prophylactic monoclonal antibodies for passive protection and for antivirals to prevent severe disease.
The researchers additionally found that the T-cell responses to vaccination among these patients displayed significant heterogeneity, just as similar studies with identical laboratory methods have found.
Also, 46.2% of the patients with antibody deficiencies had T-cell responses following vaccination that were associated with better antibody responses, although there were no differences based on which vaccine was received.
Further, patients with antibody deficiencies who received the Pfizer-BioNTech vaccine demonstrated significantly greater humoral immunogenicity compared with those who received the AstraZeneca vaccine, the researchers wrote.
In fact, 10 of the 11 vaccine breakthrough SARS-CoV-2 infections in the cohort occurred among the patients who received the AstraZeneca vaccine, with 60% experiencing no serological response to the initial two-dose vaccine schedule.
Patients with antibody deficiencies also saw positive increments in their serological and cellular responses to the SARS-CoV-2 spike protein by their second vaccine dose, which the researchers said may suggest potential benefits with additional doses.
Noting these findings, the researchers said the results of this study could be used to inform public health policy for vaccination strategies and other treatments to prevent morbidity and mortality among patients with COVID-19.
Next, the researchers plan to use detailed phenotypic and functional profiling to examine the potential correlates of vaccine immunogenicity and efficacy within the COV-AD cohort.
Perspective
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These findings are not at all surprising given what we have learned about impaired humoral responses to COVID-19 vaccines and breakthrough infection among patients receiving iatrogenic B-cell depletion. Patients with inborn errors of humoral immunity are a high-risk group, with some more than others (eg, X-linked agammaglobulinemia). This reinforces the importance of risk mitigation in this patient population, including Evusheld (tixagevimab co-packaged with cilgavimab; AstraZeneca) administration for pre-exposure prophylaxis and use of oral antivirals when infected. Future larger studies on COVID-19 outcomes in this group are needed, as are studies on immune responses after booster vaccines.
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