Affinity-Purified Respiratory Syncytial Virus Antibodies from Intravenous Immunoglobulin Exert Potent Antibody-Dependent Cellular Cytotoxicity

Abstract

Mixed infections are one of the major therapeutic challenges, as the current strategies have had limited success. One of the most common and widespread conditions of mixed infection is respiratory syncytial virus-mediated pathology of the respiratory tract in children. There is a dire need for the development of novel therapeutic approaches during mixed infections. Therapeutic intravenous immunoglobulin preparations, obtained from plasma pools of healthy donors have been used in immune deficiencies. This study was thus designed to characterize the functional efficacy of RSV-specific antibodies in IVIg. To explore the functional ability of these affinity-purified RSV-specific antibodies, the antibody-dependent and complement dependent cytotoxicity was determined using peripheral cells of healthy donors. This study demonstrates the existence of highly potent RSV-specific antibodies in IVIg preparations and provides the basis for the use of IVIg as broad-spectrum protective shield to RSV-infected children during mixed infections.

Pre-existing neutralizing antibodies prevent CD8 T cell-mediated immunopathology following respiratory syncytial virus infection

“…36 Further, human RSV-specific antibodies exhibit potent ADCC activity in vitro. 37 Thus, mAb43 administration may be contributing to the reduction of lung viral titers through either complement activation or ADCC. Motavizumab is the affinity-optimized, next-generation monoclonal antibody of its predecessor, palivizumab that binds to site II on both the pre-F and post-F confirmations of the RSV F protein.…”

Antiviral B cell and T cell immunity in the lungs

“…Functional neutralizing antibodies to respiratory viruses (including influenza virus and RSV) can be measured by plaque-reduction assays, although such methods require standardization [41][42][43] . In addition to neutralizing viruses, antibodies can also act through the ligation of Fc receptors to enable triggering of the complement cascade and antibody-dependent cell-mediated cytotoxicity 44,45 (Fig. 2).…”

Natural killer cell activation by respiratory syncytial virus‐specific antibodies is decreased in infants with severe respiratory infections and correlates with Fc‐glycosylation

“…18 Several groups have shown clearance of RSVinfected cells by peripheral blood mononuclear cells (PBMCs) in the presence of monoclonal antibodies, or antibodies from different natural sources, including breastmilk, cord blood, nasopharyngeal secretions and serum. [19][20][21][22][23] However, none of these studies shows whether killing was specifically NK cell-mediated. In addition, antibodies from RSV patients and controls have to our knowledge never been compared regarding functional properties other than neutralisation, except for antibodydependent enhancement of infection.…”