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Preexisting subtype immunodominance shapes memory B cell recall response to influenza vaccination
Rodrigo B. Abreu, Greg A. Kirchenbaum, Emily F. Clutter, Giuseppe A. Sautto, Ted M. Ross
Rodrigo B. Abreu, Greg A. Kirchenbaum, Emily F. Clutter, Giuseppe A. Sautto, Ted M. Ross
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Research Article Infectious disease Virology

Preexisting subtype immunodominance shapes memory B cell recall response to influenza vaccination

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Abstract

Influenza is a highly contagious viral pathogen with more than 200,000 cases reported in the United States during the 2017–2018 season. Annual vaccination is recommended by the World Health Organization, with the goal to reduce influenza severity and transmission. Currently available vaccines are about 60% effective, and vaccine effectiveness varies from season to season, as well as between different influenza subtypes within a single season. Immunological imprinting from early-life influenza infection can prominently shape the immune response to subsequent infections. Here, the impact of preexisting B cell memory in the response to quadrivalent influenza vaccine was assessed using blood samples collected from healthy subjects (18–85 years old) prior to and 21–28 days following influenza vaccination. Influenza vaccination increased both HA-specific antibodies and memory B cell frequency. Despite no apparent differences in antigenicity between vaccine components, most individuals were biased toward one of the vaccine strains. Specifically, responses to H3N2 were reduced in magnitude relative to the other vaccine components. Overall, this study unveils a potentially new mechanism underlying differential vaccine effectiveness against distinct influenza subtypes.

Authors

Rodrigo B. Abreu, Greg A. Kirchenbaum, Emily F. Clutter, Giuseppe A. Sautto, Ted M. Ross

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Figure 1

General experimental design.

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General experimental design.
(A) Healthy volunteers were vaccinated with...
(A) Healthy volunteers were vaccinated with the standard dose (15 μg/antigen) split-virion (IIV) version of licensed Fluzone (Sanofi Pasteur), and serum and PBMCs samples were collected prior to, 7–9, and 21–28 days following vaccination. (B) Hemagglutination inhibition activity and total HA-specific IgG were measured in serum samples collected prior to and 21–28 days following vaccination, while frequency of plasmablast were quantified in peripheral blood 7–9 days following vaccination by flow cytometry and ELISpot. PBMC samples collected prior to and 21–28 days following vaccination were differentiated in vitro, and conditioned supernatants were tested for reactivity against the 4 vaccine components to quantify the memory-derived antibody response. (C) Sampling decision tree for each assay represented in B.

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