Long-lasting protective antiviral immunity induced by passive immunotherapies requires both neutralizing and effector functions of the administered monoclonal antibody
| Autor: | Henri-Alexandre Michaud, Mireia Pelegrin, Marc Plays, Laurent Gros, Marc Piechaczyk, Roudaina Nasser |
|---|---|
| Přispěvatelé: | Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM) |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
medicine.medical_treatment
Passive immunity CD8-Positive T-Lymphocytes Antibodies Viral Virus Replication Epitopes Mice 0302 clinical medicine Viral Envelope Proteins Amino Acid Sequence Animals Animals Antigens Viral 0303 health sciences Animal Epitopes/genetics Friend murine leukemia virus/genetics/pathogenicity/physiology *Immunization Antibodies Monoclonal Passive Immunoglobulin Fc Fragments/administration & dosage/chemistry Leukemia Acquired immune system 3. Good health Friend murine leukemia virus Newborn Antibodies Antibody Viral/genetics CD8-Positive T-Lymphocytes/immunology Disease Models Monoclonal/*administration & dosage/chemistry Antibodies Immunology Molecular Sequence Data Biology Microbiology 03 medical and health sciences Immune system Antigen Immunity Virology Vaccines and Antiviral Agents medicine Animals [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Amino Acid Sequence Viral/*administration & dosage/chemistry Antigens 030304 developmental biology Leukemia Experimental Immunization Passive Immunotherapy Antibodies Neutralizing Immunoglobulin Fc Fragments Experimental/immunology/prevention & control/therapy Mice Molecular Sequence Data Retroviridae/genetics/pathogenicity/physiology Retroviridae Infections/*immunology/prevention & control/*therapy Tumor Virus Infections/immunology/prevention & control/therapy Viral Envelope Proteins/genetics/immunology Virus Replication/immunology Disease Models Animal Tumor Virus Infections Retroviridae Viral replication Animals Newborn Insect Science biology.protein Neutralizing/*administration & dosage/chemistry Antibodies 030215 immunology Retroviridae Infections |
| Zdroj: | Journal of Virology Journal of Virology, American Society for Microbiology, 2010, 84 (19), pp.10169--81. ⟨10.1128/JVI.00568-10⟩ |
| ISSN: | 0022-538X 1098-5514 |
| DOI: | 10.1128/JVI.00568-10⟩ |
| Popis: | Using FrCasEretrovirus-infected newborn mice as a model system, we have shown recently that a long-lasting antiviral immune response essential for healthy survival emerges after a short treatment with a neutralizing (667) IgG2a isotype monoclonal antibody (MAb). This suggested that the mobilization of adaptive immunity by administered MAbs is key for the success in the long term for the MAb-based passive immunotherapy of chronic viral infections. We have addressed here whether the anti-FrCasEprotective endogenous immunity is the mere consequence of viral propagation blunting, which would simply give time to the immune system to react, and/or to actual immunomodulation by the MAb during the treatment. To this aim, we have compared viral replication, disease progression, and antiviral immune responses between different groups of infected mice: (i) mice treated with either the 667 MAb, its F(ab′)2fragment, or an IgM (672) with epitopic specificity similar to that of 667 but displaying different effector functions, and (ii) mice receiving no treatment but infected with a low viral inoculum reproducing the initial viral expansion observed in their infected/667 MAb-treated counterparts. Our data show that the reduction of FrCasEpropagation is insufficient on its own to induce protective immunity and support a direct immunomodulatory action of the 667 MAb. Interestingly, they also point to sequential actions of the administered MAb. In a first step, viral propagation is exclusively controlled by 667 neutralizing activity, and in a second one, this action is complemented by FcγR-binding-dependent mechanisms, which most likely combine infected cell cytolysis and the modulation of the antiviral endogenous immune response. Such complementary effects of administered MAbs must be taken into consideration for the improvement of future antiviral MAb-based immunotherapies. |
| Databáze: | OpenAIRE |
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