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Neutrophils are essential for induction of vaccine-like effects by antiviral monoclonal antibody immunotherapies
Mar Naranjo-Gomez, … , Marc Piechaczyk, Mireia Pelegrin
Mar Naranjo-Gomez, … , Marc Piechaczyk, Mireia Pelegrin
Published May 3, 2018
Citation Information: JCI Insight. 2018;3(9):e97339. https://doi.org/10.1172/jci.insight.97339.
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Research Article Infectious disease Therapeutics

Neutrophils are essential for induction of vaccine-like effects by antiviral monoclonal antibody immunotherapies

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Abstract

Using a mouse retroviral model, we have shown that mAb-based immunotherapy can induce life-long endogenous protective immunity (vaccine-like effects). This observation has potentially important consequences for treating life-threatening human viral infections. Here, we investigated the role of neutrophils in this effect. Neutrophils are innate immunity effector cells with well-established microbe-killing activities that are rapidly mobilized upon infection. They are also emerging as orchestrators of innate and adaptive immunities. However, their immunomodulatory activity during antiviral mAb immunotherapies has never been studied. Our data reveal that neutrophils have an essential role in immunotherapy-induced immune protection of infected mice. Unexpectedly, neutrophils have a limited effect in controlling viral propagation upon passive immunotherapy administration, which is mostly mediated by NK cells. Instead, neutrophils operate as essential inducers of a potent host humoral antiviral response. Thus, neutrophils play an unexpected key role in protective immunity induction by antiviral mAbs. Our work opens approaches to improve antiviral immunotherapies, as it suggests that preserving neutrophil functions and counts might be required for achieving mAb-induced protective immunity.

Authors

Mar Naranjo-Gomez, Jennifer Lambour, Marc Piechaczyk, Mireia Pelegrin

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Figure 4

Assay of FrCasE-specific CD8+ T cells in the presence and absence of neutrophils.

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Assay of FrCasE-specific CD8+ T cells in the presence and absence of neu...
(A) Neutrophils of naive, I/NT, and I/T mice were depleted, or not, as indicated in Figure 1A. Frequency of FrCasE-specific CD8+ T cells. Spleen cells were isolated at day 14 p.i., and the frequency of virus-specific CD8+ T cells in the total CD8+ T cells population was assayed by flow cytometry using the H2Db-GagL MHC tetramer. The data represent 4 independent experiments, with at least 11 mice per group. (B) Expression of IFN-γ by CD8+ T cells. Splenic CD8+ T cells were analyzed by flow cytometry for the expression of IFN-γ. The data presented represent 3 independent experiments, with at least 7 mice per group. Data are expressed as mean ± SEM. Statistical significance was established using a parametric 1-way ANOVA test with a Bonferroni correction (*P < 0.05).

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