Antibody-Dependent Cell-Mediated Cytotoxicity against Cells Infected with Respiratory Syncytial Virus: Characterization of in Vitro and in Vivo Properties

Abstract

An in vitro 51Cr release assay for human antibody-dependent cell-mediated cytotoxicity (ADCC) against HeLa cells infected with respiratory syncytial virus (RSV) has been characterized by using leukophoresed and adherent cell-depleted adult lymphocytes. Lymphocytes from RSV seronegative children were also competent as effector cells. Sera from children with: 1) primary and recurrent natural RSV infections, or 2) live attenuated RSV vaccine infection were examined to characterize the behavior of ADCC antibody in vivo. After natural RSV infection ADCC antibody rose and fell more rapidly than neutralizing antibody. In two children undergoing primary RSV infection with attenuated vaccine, neutralizing antibody was formed in the absence of detectable ADCC antibody. The nonparallel behavior of ADCC and neutralizing antibodies suggests the heterogeneity of either the antigen involved or the mechanism of antibody production in the two antibody systems.

Difference in respiratory syncytial virus-specific Fc-mediated antibody effector functions between children and adults

“…show that ADCC drops one month after primary RSV infection in infants <1 year of age [ 40 ] and Meguro et al . show that ADCC peaks already 10 days post-infection in infants, with a rapid decline over time [ 73 ]. In studies with other viruses, it is also shown that ADCC-inducing antibodies decline rapidly after infection or, with no knowledge of prior infection, remain stable over time.…”

Fc-mediated functions and the treatment of severe respiratory viral infections with passive immunotherapy – a balancing act

“…The Fc-mediated functions of RSV-IVIG have not been assessed, but detection of RSV-specific ADCC in the respiratory tract of infants during natural infection was first reported over 40 years ago ( 68 ). RSV-specific ADCC activity was independent of symptom severity and waned rapidly compared to neutralization ( 68 , 69 ). Antibodies targeting RSV attachment (G) protein are more efficient inducers of ADCC compared to anti-RSV F protein antibodies ( 70 , 71 ).…”