Induction of long-term protective antiviral endogenous immune response by short neutralizing monoclonal antibody treatment.
Long-term immune control of viral replication still remains a major challenge in retroviral diseases. Several monoclonal antibodies (MAbs) have already shown antiviral activities in vivo, including in the clinic but their effects on the immune system of treated individuals are essentially unknown. Using the lethal neurodegeneration induced in mice upon infection of neonates by the FrCas(E) retrovirus as a model, we report here that transient treatment by a neutralizing MAb shortly after infection can, after an immediate antiviral effect, favor the development of a strong protective host immune response containing viral propagation long after the MAb has disappeared. In vitro virus neutralization- and complement-mediated cell lysis assays, as well as in vivo viral challenges and serum transfer experiments, indicate a clear and essential contribution of the humoral response to antiviral protection. Our observation may have important therapeutic consequences as it suggests that short antibody-based therapies early after infection should be considered, at least in the case of maternally infected infants, as adjunctive treatment strategies against human immunodeficiency virus, not only for a direct effect on the viral load but also for favoring the emergence of an endogenous antiviral immune response.
Gros
Laurent
L
Mireia Pelegrin: Institut de Génétique Moléculaire de Montpellier, UMR 5535-IFR 122, CNRS 1919, Route de Mende 34293, Montpellier Cedex 5, France.
Dreja
Hanna
H
Fiser
Anne Laure
AL
Plays
Marc
M
Pelegrin
Mireia
M
Piechaczyk
Marc
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000914:Antibodies, Viral / Q000097:blood / Q000627:therapeutic use*; D000918:Antibody Specificity; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D051379:Mice; D012190:Retroviridae / Q000276:immunology; D012192:Retroviridae Infections / Q000276:immunology / Q000628:therapy*; D013997:Time Factors
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral