Neutrophils are essential for induction of vaccine-like effects by antiviral monoclonal antibody immunotherapies.
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.
['Naranjo-Gomez|Mar|M|', 'Lambour|Jennifer|J|', 'Piechaczyk|Marc|M|', 'Pelegrin|Mireia|M|']
D000818:Animals D000911:Antibodies, Monoclonal D001402:B-Lymphocytes D018414:CD8-Positive T-Lymphocytes D056724:Immunity, Humoral D007113:Immunity, Innate D007167:Immunotherapy D007694:Killer Cells, Natural D009052:Leukemia Virus, Murine D004915:Leukemia, Erythroblastic, Acute D007942:Leukemia, Experimental D051379:Mice D009504:Neutrophils D012192:Retroviridae Infections D014412:Tumor Virus Infections D014779:Virus Replication
Neutrophils Immunotherapy Adaptive immunity Infectious disease Therapeutics