Efficient mother-to-child transfer of antiretroviral immunity in the context of preclinical monoclonal antibody-based immunotherapy

L. Gros , M. Pelegrin (1) , M. Plays , Marc Piechaczyk (1)

1 IGMM - Institut de Génétique Moléculaire de Montpellier

When mice under the age of 5 to 6 days are infected, the FrCas(E) retrovirus induces a neurodegenerative disease leading to death within 1 to 2 months. We have recently reported that transient treatment with a neutralizing monoclonal antibody (MAb) shortly after infection, in addition to an expected immediate decrease in the viral load, also favors the development of a strong protective immune response that persists long after the MAb has been cleared. This observation may have important therapeutic consequences, as it suggests that MAbs might be used, not only as direct neutralizing agents, but also as immunomodulatory agents enabling patients to mount their own antiviral immune responses. We have investigated whether immunoglobulins from mothers who displayed a strong anti-FrCas(E) humoral response induced upon MAb treatment could affect both viremia and the immune systems of FrCas(E)-infected pups till adult age upon placental and/or breastfeeding transfer. The strongest effects, i.e., reduction in the viral load and induction of protective humoral antiviral responses, were observed upon breastfeeding alone and breastfeeding plus placental immunity transfer. However, placental transfer of anti-FrCas(E) antibodies was sufficient to both protect neonatally infected animals and help them initiate a neutralizing anti-FrCas(E) response. Also, administration of a neutralizing MAb to naive mothers during late gestation and breastfeeding could generate similar effects. Taken together, our data support the concept that passive immunotherapies during late gestation and/or breastfeeding might help retrovirally infected neonates prime their own protective immune responses, in addition to exerting an immediate antiviral effect.

Mots clés: Viral/analysis Disease Models; Viral/blood/*immunology/therapeutic use Breast Feeding DNA; Animals Antibodies; Animal Enzyme-Linked Immunosorbent Assay Female *Immunity; Maternally-Acquired Immunization; Monoclonal/*immunology/therapeutic use Antibodies; Passive Immunoglobulin G/blood Immunologic Factors/therapeutic use Mice Neurodegenerative Diseases/*immunology Neutralization Tests Pregnancy Retroviridae/*immunology Retroviridae Infections/drug therapy/*immunology Spleen/virology Viremia

Domaines: Biochimie, Biologie Moléculaire

L. Gros, M. Pelegrin, M. Plays, Marc Piechaczyk. Efficient mother-to-child transfer of antiretroviral immunity in the context of preclinical monoclonal antibody-based immunotherapy. Journal of Virology, 2006, 80 (20), pp.10191--200. ⟨10.1128/JVI.01095-06⟩. ⟨hal-02262462⟩