M. Carolyn Hardegree

Prevention of respiratory syncytial virus infections: Indications for the use of palivizumab and update on the use of RSV-IGIV

The Food and Drug Administration recently approved the use of palivizumab (palē-vizhū-mäb), an intramuscularly administered monoclonal antibody preparation. Recommendations for its use are based on a large, randomized study demonstrating a 55% reduction in the risk of hospitalization attributable to respiratory syncytial virus (RSV) infections in high-risk pediatric patients. Infants and children with chronic lung disease (CLD), formerly designated bronchopulmonary dysplasia, as well as prematurely born infants without CLD experienced a reduced number of hospitalizations while receiving palivizumab compared with a placebo. Both palivizumab and respiratory syncytial virus immune globulin intravenous (RSV-IGIV) are available for protecting high-risk children against serious complications from RSV infections. Palivizumab is preferred for most high-risk children because of ease of administration (intramuscular), lack of interference with measles–mumps–rubella vaccine and varicella vaccine, and lack of complications associated with intravenous administration of human immune globulin products. RSV-IGIV, however, provides additional protection against other respiratory viral illnesses and may be preferred for selected high-risk children including those receiving replacement intravenous immune globulin because of underlying immune deficiency or human immuno-deficiency virus infection. For premature infants about to be discharged from hospitals during the RSV season, physicians could consider administering RSV-IGIV for the first month of prophylaxis. Most of the guidelines from the American Academy of Pediatrics for the selection of infants and children to receive RSV-prophylaxis remain unchanged. Palivizumab has been shown to provide benefit for infants who were 32 to 35 weeks of gestation at birth. RSV-IGIV is contraindicated and palivizumab is not recommended for children with cyanotic congenital heart disease. The number of patients with adverse events judged to be related to palivizumab was similar to that of the placebo group (11% vs 10%, respectively); discontinuation of injections for adverse events related to palivizumab was rare.

Tetanus toxin in dissociated spinal cord cultures: long-term characterization of form and action.

Abstract: The clinical course of tetanus is notable, in addition to its often dramatic clinical presentation, by the long duration of the neuromuscular symptoms. Survivors may have tetanic manifestations for several weeks after the onset of the disease. In this article we correlate the duration of specific electrophysiologic effects produced by tetanus toxin with the degradation of cell‐associated toxin in primary cultures of mouse spinal cord neurons. From these studies we can conclude that the toxin has a half‐life of 5–6 days. Both the heavy and the light chains of tetanus toxin degrade at similar rates. Labeled toxin, visualized by radioautography, is associated with neuronal cell bodies and neurites, and its distribution is not altered during a 1‐week period following toxin exposure. Blockade of synaptic activity persists for weeks at the concentration of radiolabeled toxin used in these studies. This blockade of transmission is reversed as the toxin is degraded, suggesting that degradation of toxin may be a sufficient mechanism for recovery from tetanus.

Cholesterol-dependent tetanolysin damage to liposomes

Tetanolysin caused membrane damage, resulting in release of trapped glucose from liposomes containing cholesterol. Maximum glucose release occurred from liposomes that contained 50 mol% cholesterol. At higher or lower levels of cholesterol, glucose release was reduced and glucose release did not occur at all below 40 mol% cholesterol. The apparent activity of tetanolysin was not influenced by temperature (24 degrees C compared to 32 degrees C) or by liposomal phospholipid fatty acyl chain length. We conclude that tetanolysin caused cholesterol-dependent lysin-mediated damage to liposomes, possibly by means of a pore consisting of a complex of toxin and cholesterol.

Heterogeneity of 125I-labeled tetanus toxin in isoelectric focusing on polyacrylamide gel and polyacrylamide gel electrophoresis

Abstract Tetanus toxin isolated from Clostridium tetani and radioiodinated by both the Hunter-Greenwood and the Bolton-Hunter procedures was analyzed by isoelectric focusing on Polyacrylamide gel and by “quantitative” gel electrophoresis. Immediately after iodination, the focused preparation exhibited a single protein component with a p I ′ of 5.1, while after storage it was progressively transformed into a protein with a p I ′ of 5.9. Formation of the second component could not be prevented by storage in liquid nitrogen (−196 °C). Although polyacrylamide gel electrophoresis at either pH 3.7 or 11.0 did not reveal this heterogeneity, it provided physical parameters describing molecular size and net charge, by which the molecule can be recognized.

Induction of interferon by bacterial vaccines and allergenic extracts

Licensed bacterial vaccines with no specific United States standard of potency and allergenic extracts were examined for their ability to induce interferon, an antiviral protein. Samples representative of these products were injected into mice and interferon production was tested by titration of mouse sera with the use of a standard vesicular stomatitis virus yield reduction method in primary mouse embryo fibroblast cell cultures. Antiviral activity was assessed by challenge with a lethal dose of Semliki Forest virus. High levels of circulating interferon were induced by certain of the bacterial vaccines and allergenic extracts. Interferon was detected when the intravenous route of inoculation was used and in certain instances after subcutaneous administration. The time of appearance and the duration of the interferon production were similar to those reported for endotoxin. There was also a second interferon-inducing component in some of these products. Experiments in which mice were challenged with Semliki Forest virus demonstrated that the levels of interferon induced by selected products provided a high degree of protection against the virus challenge. Thus, a new activity, the induction of interferon, has been found for certain of these vaccines and extracts. The data suggest that investigations be performed to explore the possible significance of the results derived in the mouse system for man.

Effect of allergenic extracts of house dust and bacterial vaccine on respiratory infections of mice

Abstract Allergenic extracts of house dust and a bacterial vaccine with no U. S. standard of potency were examined for their capacity to protect mice against respiratory virus infections. A single intravenous injection of house dust extract resulted in the recovery of significantly less of the Sendai strain of parainfluenza virus from the lungs of mice after aerosol challenge than did an injection of saline. Multiple subcutaneous injections of house dust extract protected more mice against an aerosol challenge of Sendai virus than did a single subcutaneous dose. This increased level of protection was not associated with an increased level of circulating interferon. A single intravenous injection of bacterial vaccine did not protect mice against an aerosol challenge with Sendai virus. Mice were not significantly protected against challenge with influenza viruses by either house dust extract or bacterial vaccine. Although both of these types of products have been shown to be capable of inducing interferon in mice, presumably because they contain endotoxin, the induction of interferon may not be the only mechanism for any antiviral protective effect observed.