B-Cell Immunophenotyping to Predict Vaccination Outcome in the Immunocompromised-A Systematic Review

Annieck M. Diks, Lisanne A. Overduin, Laurens D. van Leenen, Lennert Slobbe, Hetty Jolink, Leonardus G. Visser, Jacques J. M. van Dongen, Magdalena A. Berkowska

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Vaccination is the most effective measure to prevent infections in the general population.
Its efficiency strongly depends on the function and composition of the immune system. If
the immune system lacks critical components, patients will not be fully protected despite a
completed vaccination schedule. Antigen-specific serum immunoglobulin levels are
broadly used correlates of protection. These are the products of terminally differentiated
B cells – plasma cells. Here we reviewed the literature on how aberrancies in B-cell
composition and function influence immune responses to vaccinations. In a search
through five major literature databases, 6,537 unique articles published from 2000 and
onwards were identified. 75 articles were included along three major research lines:
extremities of life, immunodeficiency and immunosuppression. Details of the protocol can
be found in the International Prospective Register of Systematic Reviews [PROSPERO
(registration number CRD42021226683)]. The majority of articles investigated immune
responses in adults, in which vaccinations against pneumococci and influenza were
strongly represented. Lack of baseline information was the most common reason of
exclusion. Irrespective of study group, three parameters measured at baseline seemed to
have a predictive value in assessing vaccine efficacy: (1) distribution of B-cell subsets
(mostly a reduction in memory B cells), (2) presence of exhausted/activated B cells, or B
cells with an aberrant phenotype, and (3) pre-existing immunological memory. In this
review we showed how pre-immunization (baseline) knowledge of circulating B cells can
be used to predict vaccination efficacy. We hope that this overview will contribute to
optimizing vaccination strategies, especially in immunocompromised patients.
Original languageEnglish
Article number690328
Number of pages21
JournalFrontiers in Immunology
Publication statusPublished - 7 Sep 2021


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