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Selective induction of antibody effector functional responses using MF59-adjuvanted vaccination
Carolyn M. Boudreau, … , Kathryn M. Edwards, Galit Alter
Carolyn M. Boudreau, … , Kathryn M. Edwards, Galit Alter
Published December 17, 2019
Citation Information: J Clin Invest. 2020;130(2):662-672. https://doi.org/10.1172/JCI129520.
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Research Article Immunology

Selective induction of antibody effector functional responses using MF59-adjuvanted vaccination

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Abstract

Seasonal and pandemic influenza infection remains a major public health concern worldwide. Driving robust humoral immunity has been a challenge given preexisting, often cross-reactive, immunity and in particular, poorly immunogenic avian antigens. To overcome immune barriers, the adjuvant MF59 has been used in seasonal influenza vaccines to increase antibody titers and improve neutralizing activity, translating to a moderate increase in protection in vulnerable populations. However, its effects on stimulating antibody effector functions, including NK cell activation, monocyte phagocytosis, and complement activity, all of which have been implicated in protection against influenza, have yet to be defined. Using systems serology, we assessed changes in antibody functional profiles in individuals who received H5N1 avian influenza vaccine administered with MF59, with alum, or delivered unadjuvanted. MF59 elicited antibody responses that stimulated robust neutrophil phagocytosis and complement activity. Conversely, vaccination with MF59 recruited NK cells poorly and drove moderate monocyte phagocytic activity, both likely compromised because of the induction of antibodies that did not bind FCGR3A. Collectively, defining the humoral antibody functions induced by distinct adjuvants may provide a path to designing next-generation vaccines that can selectively leverage the humoral immune functions, beyond binding and neutralization, resulting in better protection from infection.

Authors

Carolyn M. Boudreau, Wen-Han Yu, Todd J. Suscovich, H. Keipp Talbot, Kathryn M. Edwards, Galit Alter

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Figure 3

MF59 induces neutralization and specific antibody-dependent innate immune functions along with IgG1 titers.

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MF59 induces neutralization and specific antibody-dependent innate immun...
(A) HAI activity for serum samples in all 3 vaccine groups over 4 time points (11). Each dot represents the average of 2 replicates for 1 serum sample. For all dot plots, bar shows group mean. The dotted line indicates the limit of detection. (B) HAI activity divided by total IgG Luminex MFI as reported in Figure 2 for all 3 vaccine groups during the 3 post-vaccine time points. For all box plots, error bars show minimum to maximum. (C) Microneutralization (MN) activity for serum samples (11). Each dot represents the average of 2 replicates for 1 serum sample. The dotted line indicates the limit of detection. (D) MN activity divided by total IgG Luminex MFI for all 3 vaccine groups. (E) Average ADNP activity for serum samples across 2 healthy WBC donors. Each dot represents the average of 2 replicates for 1 serum sample. The dotted line indicates flu-negative serum background. (F) ADNP activity divided by total IgG Luminex MFI for all 3 vaccine groups. (G) ADCD by serum samples. Each dot represents the average of 2 replicates for 1 serum sample. The dotted line indicates the flu-negative serum background. Values are indicated as the average area under the curve of 3 serum dilutions run in 2 independent replicates. (H) ADCD activity divided by total IgG Luminex MFI. Significance was tested by 2-way ANOVA followed by Tukey’s multiple comparisons test. Significance was only noted within time point. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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