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Fourth mRNA COVID-19 Vaccination in Immunocompromised Patients with Hematologic Malignancies
23 Pages Posted: 6 Mar 2023More...
Background: Patients with hematologic malignancies have impaired antibody responses to SARS-CoV-2 vaccination. We aimed to investigate whether a fourth mRNA COVID-19 vaccination improved antibody quantity and quality.
Methods: In this cohort study we quantified SARS-CoV-2-specific antibody concentration and neutralizing activity in SARS-CoV-2 naive, immunocompromised patients with hematologic malignancies who received 4 COVID-19 mRNA vaccinations.
Findings: 414 patients with hematologic malignancies were included in our analyses. Although S1 IgG concentrations significantly improved after the fourth dose, they remained significantly lower compared to those obtained by age-matched healthy individuals after their first booster (third) vaccination. The rise in neutralizing antibody concentration was most prominent in patients with a recovering B cell compartment, although potent responses were also observed in some patient groups with persistent immunodeficiencies. 19% of patients did not seroconvert despite 4 vaccinations. Patients who received their first 2 vaccinations when they were B cell depleted and the third and fourth vaccination during B cell recovery demonstrated similar antibody induction dynamics as patients with normal B cell numbers during the first 2 vaccinations. However, the neutralizing capacity of these antibodies was significantly better than that of patients with normal B cell numbers after two vaccinations.
Interpretation: A fourth mRNA COVID-19 vaccination improved S1 IgG concentrations in the majority of patients with a hematologic malignancy. Vaccination during B cell depletion may pave the way for better quality of antibody responses after B cell reconstitution.
Funding: The Netherlands Organisation for Health Research and Development and Amsterdam UMC.
Declaration of Interest: None of the authors declare competing financial interests.
Ethical Approval: Study protocols were approved by the Institutional Review Board of Amsterdam UMC location Vrije Universiteit and participating centers (COBRA-KAI study) and Utrecht University (VITAL cohort). All patients provided written informed consent.
Keywords: Humoral immunogenicity, Antibody response, SARS-CoV-2, COVID-19 vaccination, Booster vaccination, Hematologic malignancies, Immunocompromised
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