A Crucial Role for Infected-Cell/Antibody Immune Complexes in the Enhancement of Endogenous Antiviral Immunity by Short Passive Immunotherapy

• DOI: 10.1371/journal.ppat.1000948
• Publication Date: 2010-06-10T20:31:24Z
• Authors: Henri-Alexandre M...; Tiphanie Gomard; Laurent Gros; Kevin Thiolon; Roudaina Nasser; Chantal Jacquet; Javier Hernandez; Marc Piechaczyk; Mireia Pelegrin
• Keywords: 0303 health sciences; Cytotoxic; QH301-705.5; Antibody-Dependent Cell Cytotoxicity; Immunization, Passive; Antibodies, Monoclonal; Antigen-Antibody Complex; RC581-607; Antibodies, Viral; Flow Cytometry; 3. Good health; immunology; Mice; 03 medical and health sciences; Retroviridae; Animals Antibodies; Animals; [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology; Immunologic diseases. Allergy; Biology (General); Research Article; Cell Proliferation; Retroviridae Infections; T-Lymphocytes, Cytotoxic

Antiviral monoclonal antibodies (mAbs) represent promising therapeutics. However, most mAbs-based immunotherapies conducted so far have only considered the blunting of viral propagation and not other possible therapeutic effects independent virus neutralization, namely modulation endogenous immune response. As induction long-term antiviral immunity still remains a paramount challenge for treating chronic infections, we asked here whether neutralizing mAbs can, in addition to propagation, exert immunomodulatory with protective outcomes. Supporting this idea, report that mice infected FrCasE murine retrovirus on day 8 after birth die leukemia within 4–5 months mount non-protective response, whereas those rapidly subjected short immunotherapy mAb survive healthy long-lasting strong humoral cellular responses. Interestingly, administered mediates lysis cells through an antibody-dependent cell cytotoxicity (ADCC) mechanism. In addition, it forms complexes (ICs) enhance CTL responses FcγR-mediated binding dendritic (DCs). Importantly, generated mAb-treated also display same properties, allowing containment enhancement memory disappearance mAb. Thus, our data demonstrate can act as agents capable stimulating lasting long end treatment. They show important role infected-cells/antibody maintenance both primary T-cell indicate targeting cells, just viruses, by be crucial elicitation efficient, This must when designing mAb-based immunotherapies.