Hyperimmune globulins in prevention and treatment of respiratory syncytial virus infections

Abstract

Respiratory syncytial virus (RSV) is an important community and nosocomial respiratory pathogen for infants and young children. RSV causes especially severe disease in the prematurely born or those with chronic cardiopulmonary diseases. Elderly persons and those with T-cell deficiencies, such as bone marrow transplant recipients, are also at high risk for serious lower respiratory tract infections. To date, prevention of RSV infections by vaccination has proven elusive and no preventive drugs exist. Studies in animals and humans have shown that the lower respiratory tract can be protected from RSV infection by sufficient circulating RSV neutralizing antibody levels. Recently, an RSV hyperimmune immune globulin (RSVIG) was developed and tested for the prevention of RSV infections or reduction of disease severity. Passive immunization of high-risk children with RSVIG during the respiratory disease season effected significant reductions in RSV infections, hospitalizations, days of hospitalization, intensive care unit admissions, days in the intensive care unit, and ribavirin use. Studies in cotton rats and owl monkeys show that RSV infections can also be treated with inhalation of immune globulin at doses substantially smaller than required for parenteral treatment. Therapeutic trials of parenteral RSVIG have been completed and are pending analysis. The use of polyclonal, hyperimmune globulins and perhaps human monoclonal antibodies provides an additional approach to the prevention and perhaps the treatment of certain viral lower respiratory tract infections such as those caused by RSV.

Protective Efficacy against Respiratory Syncytial Virus following Murine Neonatal Immunization with BBG2Na Vaccine: Influence of Adjuvants and Maternal Antibodies

“…Passively transferred antibodies can confer protection from RSV disease both in humans [35] and in murine models of maternal immunization with BBG2Na [19]. However, the protection conferred by maternal antibodies is transient, and prolonged protection requires associated infant immunization.…”

Therapy for respiratory tract infections caused by respiratory syncytial virus

“…In the search for alternatives, hyperimmune globulins with higher neutralising antibody titre against RSV (RSVIG) were developed. It proved that RSVIG indeed could provide better neutralising antibody titres [22,28]. In a randomised prevention trial, monthly administered high dose intravenous RSVIG proved to be bene®cial in terms of rate of hospitalisation, duration of hospitalisation and duration on the intensive care unit in children at high risk for severe RSV infection [21].…”

“…It was suggested that with standard IVIG used in these studies insucient neutralising antibody titres were achieved. This was also the case in several other lots of standard IVIG tested [28]. In the search for alternatives, hyperimmune globulins with higher neutralising antibody titre against RSV (RSVIG) were developed.…”

“…In contrast to these clear immunopathogenetic eects of the cellular immune response, a pre-existing humoral response is mainly associated with protection against RSV infection. Several studies have demonstrated that the risk of LRTI is inversely related to the titre of neutralising antibodies [28]. However, there are also indications that besides this protective eect, parts of the humoral immune response may be associated with the pathogenesis of RSV bronchiolitis [34].…”

Immune‐Globulin Prophylaxis of Respiratory Syncytial Virus Infection in Patients Undergoing Stem‐Cell Transplantation

“…SCT recipients are at high risk of infectious complications during the immediate posttransplantation period. RSV infections during this time spread from the upper to the lower respiratory tract in 60% of cases, with an associated 60%-80% mortality [2].Studies in cotton rats and in infants have shown that IgG with a high titer of neutralizing antibody to RSV decreases the incidence of RSV spread from the upper to the lower respiratory tract [3][4][5]. Studies in infants have shown that monthly infusions of immune globulin (750 mg/kg) with high neutralizing antibody titers decreases the incidence of hospitalization for RSV lower-respiratory-tract infection in premature infants !6 months of age and in children !24 months of age with bronchopulmonary dysplasia, compared with untreated control subjects [6].…”