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

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 6

MF59-induced antibody functionality is not influenced by prevaccination H1-specific immunity.

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MF59-induced antibody functionality is not influenced by prevaccination ...
(A) Samples were grouped into low, mid, or high based on their baseline (day 0) H1-specific ADCP. The dot plot indicates grouping strategy of baseline H1-specific ADCP among each vaccine group. (B) H5-specific ADCP at peak immunogenicity (day 56) for H1 baseline ADCP groups. (C) H1-specific ADCP at peak immunogenicity for each baseline reactivity group by vaccine adjuvant. (D) Samples were grouped into low, mid, or high based on their baseline (day 0) H1-specific ADNP. The dot plot indicates the grouping strategy of baseline H1-specific ADNP among each vaccine group. (E) H5-specific ADNP at peak immunogenicity (day 56) for H1 baseline ADNP groups. (F) H1-specific ADNP at peak immunogenicity for each baseline reactivity group by vaccine adjuvant. (G) Samples were grouped into low, mid, or high based on their baseline (day 0) H1-specific ADCD. Dot plot indicates grouping strategy of baseline H1-specific ADCD among each vaccine group. (H) H5-specific ADCD at peak immunogenicity (day 56) for H1 baseline ADCD groups. (I) H1-specific ADCD at peak immunogenicity for each baseline reactivity group by vaccine adjuvant. For all dot plots, each dot represents the average of 2 replicates for 1 serum sample, and bar shows group mean. Significance was tested by 2-way ANOVA followed by Tukey’s multiple comparisons test and is noted only within time point. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.