Monoclonal antibodies (mAbs) are the largest class of biomedicines. Administered to neutralize and eliminate pathogens, they can also induce a lasting immune response, such as vaccination. The work of Mar Naranjo-Gomez et al., In the team “Oncogenesis and Immunotherapy” has demonstrated an unexpected role of a type of leukocytes, neutrophils, in the therapeutic efficacy of mAbs. These cells of the innate immune system, have an essential role in the elimination of pathogens and, in addition to their microbicidal power, have recently emerged as key cells in the orchestration of immune responses. By using a murine model of persistent viral infection, the work of Mar Naranjo-Gomez et al., showed a crucial role of neutrophils in inducing vaccine-like effects. Notably, during immunotherapy with mAb, they acquire immunomodulatory properties and induce a strong and long-lasting protective antiviral humoral response. This work opens new avenues to improve antiviral immunotherapies. They suggest that preserving the functions and amount of circulating neutrophils may be necessary to obtain protective immunity induced by antiviral mAbs.
Immunotherapy of mice infected with a neutralizing mAb induces a life-long protective immunity. This protection involves different cells of the immune system. On the one hand, the mAb recruits NK cells which have a key role in the control of viral propagation, in particular via the lysis of infected cells targeted by the mAb. On the other hand, in the presence of therapeutic mAb, neutrophils recruited at infection sites acquire immunomodulatory properties and become orchestrators of the antiviral immune response. In particular, they produce molecules involved in the induction of a strong humoral response, such as lymphotoxin α (LTα) and B-cell activating factor (BAFF), resulting in the production of endogenous antibodies.
Neutrophils are essential for induction of vaccine-like effects by antiviral monoclonal antibody immunotherapies.
Naranjo-Gomez M, Lambour J, Piechaczyk M, Pelegrin M.
JCI Insight. 2018 May 3;3(9). pii: 97339. doi: 10.1172/jci.insight.97339.
