Zoster Immune Globulin Research Articles

IgG subclass distribution among antibodies to varicella-zoster virus in human varicella/zoster immunoglobulin preparations and the corresponding donor plasma

IgG subclasses to varicella-zoster virus (VZV) were detected in plasma from different sources used for the production of varicella/zoster immunoglobulin (VZIG). IgG1 and IgG3 were the principal virus antibodies in plasma from healthy donors as well as from convalescents after primary and reactivated disease. Anti-VZV IgG3 antibodies were predominant among varicella convalescents while IgG1 antibodies dominated among zoster convalescents. IgG4 antibodies were present in zoster convalescents and healthy donors but were rarely detected in varicella convalescents. Antiviral IgG2 antibodies were found only in a few cases. Studies of plasma samples collected from one varicella convalescent during a period of seven months following an outbreak of disease, demonstrated a rapid fall in antiviral IgG1 and IgG3, while IgG4 increased to reach a maximum six months after the onset of symptoms. The relative distribution of VZV-specific subclasses in a plasma pool was conserved during a fractionation procedure combining polyethyleneglycol 6000 precipitation with ion exchange chromatography, thus suggesting that the protective efficacy is maintained in the resulting immunoglobin preparations.

Comments on vaccines, August 1987

Because of latency and infectious recurrences, eradication of herpes simplex and herpes zoster from the world by vaccines is likely to be much more difficult to accomplish than eradication of smallpox. For some time we may have to settle for control of these diseases rather than their eradication. The live, attenuated varicella vaccine protects immunocompromised and normal persons against clinical chickenpox but it does not completely prevent subsequent infection with natural chickenpox virus or latency. With herpes simplex vaccines we may have to be satisfied with amelioration or control of clinical infections and diminution of latency and recurrent disease. Varicella zoster immune globulin plays a useful role in attenuation of varicella in immunocompromised or special-risk persons exposed to varicella zoster virus. Passive immunization for herpes simplex (herpes simplex immune globulin or other antibody preparations) has been studied very little. Maybe passive immunization will have a place in future therapies, especially for serious herpes simplex virus infections in immunocompromised hosts.

Varicella zoster antibody testing in the care of pregnant women exposed to varicella

Appropriate use of varicella zoster immunoglobulin to prevent or ameliorate maternal or perinatal infection depends on accurate identification of varicella-susceptible women. Detection of fluorescent antibody to varicella zoster virus membrane antigen is an available means for identifying women exposed to varicella who are at risk for infection. During a 5 1/2-year period, 37 pregnant women who had been exposed to varicella and who had a negative or indeterminate history of prior varicella were tested for the presence of varicella zoster virus membrane antigen. Among the 17 women with a negative history, 12 (71%) had a positive test result and five (29%) had a negative test result. Among 20 women with undeterminant histories, 18 (90%) were immune and two (10%) were susceptible. Three additional women who were tested despite a history of varicella had positive varicella zoster virus membrane antigen test results. Overall, 81% of patients with a negative or uncertain history of varicella had serologic evidence of past varicella. One of six untreated seronegative women and one weakly positive woman developed disease. There was no instance of congenital varicella. Expeditious determination of varicella zoster virus membrane antigen or equivalent anti-varicella antibody status in pregnant women exposed to varicella appears to be a rapid, satisfactory method for determining who should promptly receive varicella zoster immunoglobulin passive immunization.

Varicella zoster immunoglobulin after postnatal exposure to varicella

A questionnaire based on a hypothetical 6-day-old infant exposed to a sibling with varicella was mailed to 316 Pediatric Infectious Diseases Society members to determine their recommendations for administration of varicella zoster immunoglobulin (VZIG). Of the 137 faculty members who responded 20% would recommend VZIG for the infant described (13% were undecided). When further information including a negative maternal history for varicella, prematurity or maternal varicella infection occurring 1 week after delivery was considered, the numbers who recommended VZIG (43, 46 and 52%, respectively) rose significantly (P less than 0.01). Twenty-two physicians had knowledge of a severe case of varicella following postnatal exposure. Only 33% of faculty members surveyed feel there are no indications for VZIG in infants exposed after 48 hours of age.

Incidence of chickenpox in adults and recruitment of plasma donors for manufacture of zoster immunoglobulin.

Incidence of chickenpox in adults and recruitment of plasma donors for manufacture of zoster immunoglobulin.

The potency determination of human varicella-zoster immunoglobulin by enzyme-linked immunosorbent assay, complement-fixation test and indirect fluorescent antibody tests

Traditionally, plasma for the production of the human varicella-zoster immunoglobulin (VZIG) has been selected on the basis of the complement-fixing antibody (CFA) titre. Since immune individuals may lack CFA to varicella-zoster virus (VZV), non-CFA may be of importance in protection. In a search for a simple and reliable method for potency determination, 24 VZIG preparations were quantified by enzyme-linked immunosorbent assay (ELISA), the complement-fixation test (CFT), the indirect fluorescent antibody test to acetone-fixed (IF) and viable (FAMA) VZV-infected cells, respectively. The antibody titres obtained by the various methods were compared. Arranged in order of decreasing agreement, the correlation coefficients ( r) of the regression equations between the variables were 0·62 for CFT and FAMA, 0·50 for CFT and ELISA and 0·26 for CFT and IF in a log 2 plot. There was complete agreement between the titres obtained by the commercially available Enzygnost ® Varicella/Zoster kits (Behring Institute, Marburg, F. R. Germany) and the ELISA microtitre plates produced at our institute ( r = 1). The regression equation lines for ELISA/CFT and FAMA/CFT titres tended to be parallel to each other, while the line for IF/CFT titres had a less steep slope. Similar titration curves were obtained for VZIGs fractionated by two different methods. Furthermore, the titration curves of serum pools from varicella and zoster convalescents, respectively, had a similar shape below ΔOD = 0·4. Generally, a steeper slope was observed above ΔOD = 0·4. As antibody detectable by ELISA seems to correlate with protection and the method is sensitive, specific, reproduceable, simple to carry out and easily automated, it may be suitable for the potency determination of VZIGs.

Chickenpox prevention in patients at risk with a special immunoglobulin

Chickenpox, which normally is an innocuous disease in children, may cause serious sequelae in immunocompromised hosts. An open prospective study is presented, that comprised 96 of such patients. They were treated with 0,2 ml/kg Varicella-Zoster-Immunoglobulin (VZIG) prophylactically or after exposure. The immunoglobulin was given in between 72 hours after known contact, newborns received the injection at the day of delivery. After that the patients were followed for six weeks for documentation and assessment of protection. In 85 (88,5%) cases there was no manifestation of varicella. 10 patients showed mild forms of the disease; 3 of these had got the preparation within the recommended time gap of 72 hours after exposure. One child died from varicella pneumonia and haemorrhage. In this case the preparation had only been given 10 days after contact.

Effect of zoster immunoglobulin for varicella prophylaxis in the newborn.

Zoster immunoglobulin (ZIG) was given for prophylaxis to 95 neonates born to mothers with perinatal varicella. The treatment had no influence on the clinical attack rate; 48 (50%) of the children developed varicella. However, the ZIG treatment clearly influenced the course of the disease for newborns at particular risk, i.e. when maternal varicella developed within 4 days before and 2 days after delivery. Of 41 such neonates, 21 (51%) contracted varicella with an incubation mean time of 11 days. 13 of the 21 developed a very mild chickenpox (no fever, less than or equal to 20 pocks), 6 had a mild to normal disease, and 2 (10%) had more severe infections; none died or got sequelae after the disease. These results should be compared with the expected rate of complications in non-treated neonates in the defined risk group, where the mortality among those contracting varicella has been reported to be as high as about 30%.

Treatment of Herpes Zoster by Zoster Immune Globulin

Treatment of Herpes Zoster by Zoster Immune Globulin

Comparison of varicella zoster antibody titers in patients given intravenous immune serum globulin or varicella zoster immune globulin

We compared the VZV IgG antibody titers after administration of varicella zoster immune globulin and serum immune globulin intravenously (IGIV) in VZV seronegative pediatric patients with cancer. Four patients received VZIG at standard doses; four received IGIV at 4 ml/kg every 4 weeks for four doses; and five received IGIV at 6 ml/kg every 6 weeks for two to four doses. VZV antibody titers were measured by radiommunoassay (RIA), enzyme-linked immunosorbent assay (ELISA), indirect fluorescent antibody assay (IFA), and neutralizing antibody assay. The mean peak and trough VZV titers by RIA were comparable in all three groups: 1:724 at 4 weeks after VZIG, 1:2048 at 4 weeks after 4 ml/kg IGIV, and 1:776 at 6 weeks after 6 ml/kg IGIV. The titers measured by ELISA, IFA, and neutralizing antibody were comparable after VZIG or IGIV. The VZV titers by RIA were maintained at greater than or equal to 1:1024 after subsequent doses of 4 ml/kg IGIV, and at greater than or equal to 1:256 after subsequent doses of 6 ml/kg IGIV. Adverse effects were rare. The VZV antibody titers assessed 4 to 6 weeks after IGIV administration were equivalent to the titers measured 4 weeks after administration of VZIG.

A spell of chicken-pox on a cancer patients' ward.

Second episodes of varicella after a definite primary exposure to chicken-pox are well known in immunosuppressed children. We report an outbreak in adult cancer patients. This observation suggests that there is also a higher risk of varicella infection in immunosuppressed adults. As there is a trend for a pronounced severity of chicken-pox in patients receiving anticancer drugs or suffering from immunosuppressive diseases, the prophylactic use of varicella zoster immune globulin in adult patients has to be discussed, especially as positive experiences with children were recently gained. Following manifestation, therapy with systemic aciclovir seems to be effective.

Varicella zoster antibody titers after the administration of intravenous immune serum globulin or varicella zoster immune globulin

Varicella is a serious infection in the immunocompromised patient. Prophylaxis with varicella zoster immune globulin is known to decrease the incidence of severe varicella infection. The titers of antibody to varicella zoster virus were compared in patients who received either varicella zoster immune globulin or intravenous immune globulin, 4 ml or 6 ml/kg per dose. The titers of antibody to varicella zoster virus were comparable in each group.

Varicella-zoster antibody titers in children with leukemia and lymphoma. Relationship of titer to varicella-zoster infection.

Serum varicella-zoster (VZ) antibody titers were determined by a simple, indirect immunofluorescent antibody technique in 50 children with leukemia or non-Hodgkin's lymphoma. Sixteen children had initial antibody titers that were not detectable at a serum dilution of 1:8 and were considered to be susceptible to varicella. Thirty-one patients had initial serum VZ antibody titers of 1:16 or greater, while three had levels of 1:8. The serum antibody titer was 1:8 or greater in 16 children with a history of varicella. Seven episodes of localized herpes zoster were observed in children whose VZ titer was 1:8 or greater prior to onset. Two nonfatal infections with primary varicella developed in children with leukemia in remission whose initial titers were less than 1:8 and were associated with a convalescent rise in VZ antibody to levels greater than 1:16. Three susceptible children received zoster immune plasma or zoster immune globulin for varicella exposure, causing a transient rise in serum VZ titer. The assessment of serum VZ titer by this immunofluorescent antibody technique combined with the prior varicella history is useful in defining the population of children with leukemia and non-Hodgkin's lymphoma who are susceptible to primary varicella.

Zoster Immunoglobulin in Varicella Prophylaxis: A Study among High-Risk Patients

The efficacy of zoster immunoglobulin (ZIG) in preventing varicella was studied among patients in a high-risk group. 173 non-immune patients were observed after exposure to varicella-zoster (VZ) virus and subsequent administration of ZIG. For 138 patients (80%) no sign of varicella was recorded, 16 patients (9%) had a subclinical infection and 19 patients (11%) developed varicella. 12/19 patients with varicella contracted a very mild disease (less than 20 pocks, negligible fever), 5 got mild or normal disease and 2 children, both with acute lymphatic leukemia, developed more pronounced symptoms. Three patients protected by 0.15 ml ZIG/kg body weight after heavy exposure to VZ virus, were not protected at a second exposure 2 weeks later. In an enlarged study group of high-risk patients where 52 patients receiving ZIG developed varicella, the mean incubation period for 42 patients was 21 days. Leukemic patients were found to have a higher frequency of clinical varicella, more pronounced symptoms and a slightly longer incubation period than other high-risk patients. VZ specific antibody titers were compared for various immunoglobulin preparations and found to be 30 times higher in zoster immunoglobulins than in normal immunoglobulins.

Expanded Guidelines for Use of Varicella-Zoster Immune Globulin

I. BACKGROUND INFORMATION 1. Zoster Immune Globulin Zoster immune globulin (ZIG) can prevent clinical chickenpox in exposed, susceptible, normal children.1 In a collaborative study2 in which 15 susceptible children at high risk received ZIG within three days following exposure, there were no deaths and only one child developed progressive varicella. At that time, a mortality of 7% and a rate of progressive varicella of 30% were reported in similar children who failed to receive prophylaxis.3 At the present time, varicella may be even more hazardous for children with leukemia, possibly because of the use of more intensive therapy. 2. Varicella-Zoster Immune Globulin The use of plasma obtained from patients convalescing from zoster to prepare ZIG resulted in a limited supply of this material. The finding that plasma from normal donors with high varicella-zoster (V-Z) antibody could be used to prepare a globulin of similar potency, referred to as varicella-zoster immune globulin (VZIG),4 now assures ample supply. The availability of this material, through the American Red Cross, permits us to recommend it for additional indications. The major deterrent to the use of VZIG is its cost, which in August 1983 was approximately $75 per 125 units (approximately 1.25 mL), the dose for a 10-kg child. The recommended adult dose of 625 units costs about $375. 3. Morbidity from Varicella in Adults Adults suffer greater morbidity from chickenpox than do children. Although less than 2% of reported cases occur in individuals after the second decade, nearly one quarter of all the reported mortality occurs in this group.5 Of particular concern are pregnant women who develop chickenpox.

Varicella zoster virus antibody titers before and after administration of zoster immune globulin to neonates in an intensive care nursery

Varicella zoster virus antibody titers before and after administration of zoster immune globulin to neonates in an intensive care nursery

Prolonged excretion of herpesvirus varicellae in a child with acute lymphoblastic leukaemia

An eight-year-old girl with acute lymphoblastic leukaemia (ALL) in remission presented with varicella. Zoster immune globulin was not given, but treatment with acyclovir was commenced the day after presentation and continued for five days. Many of the original vesicles ulcerated and persisted for periods in excess of three months, finally leaving residual scarring. Further new vesicles appeared at 80 days and 109 days, and virus was again visualised by electron microscopy. Seroconversion was not demonstrated, although the child has in the past responded serologically to other viruses. A series of other infections afflicting the child at about the same time is documented and the possible implications are discussed.

Antibody-dependent cell-mediated cytotoxicity against varicella-zoster virus-infected targets.

Antibody-dependent cell-mediated cytotoxicity (ADCC) against cryopreserved varicella-zoster virus-infected human foreskin fibroblasts was detected in a 51Cr release assay. Target cells, samples of seropositive or seronegative sera, and mononuclear cells obtained by Ficoll-Hypaque centrifugation of human peripheral blood were added to microtiter plate wells and allowed to incubate at 37 degrees C for 4 h. Fibroblasts infected for 48 to 96 h were susceptible to ADCC. Effector cells from seropositive and seronegative normal children were equally active in the assay. Antibody titers were determined by testing serial dilutions of sera in the ADCC assay. Zoster immune globulin had a titer of 204,800. Sera from 40 naturally seropositive individuals were compared by assays for ADCC and fluorescent antibody to membrane antigen. All sera that were negative by fluorescent antibody to membrane antigen (less than 2) were also negative by ADCC (less than 20). All sera that were positive by fluorescent antibody to membrane antigen were also positive by ADCC, but titers of individual sera were frequently 5 to 20 times higher in the ADCC assay.

Frequency and specificity of varicella zoster virus IgM response

A direct ELISA was developed for determination of IgM antibody to varicella zoster virus (VZV). With this sensitive method VZV IgM antibodies were detected in all patients with a varicella and in 84% with a herpes zoster infection. All but one of 28 renal allograft recipients had previously had varicella. A primary infection was seen in the last patient, and reactivated infections in 11 of the others. The VZV IgM response seems to be specific since patients with a herpes simplex virus (HSV) infection and a heterotypic VZV IgG titer rise did not have detectable VZV IgM. An indirect enzymelinked immunosorbent assay (ELISA) for detection of IgG antibodies has been used for serodiagnosis of VZV infections and to determine the immune status. After injection of zoster immune globulin, it was possible to measure passively transferred antibodies.

Acyclovir therapy of chickenpox in immunosuppressed children—A collaborative study

A randomized double-blind, placebo-controlled, multicenter investigation assessed the usefulness of acyclovir in the treatment of immunosuppressed children with chickenpox. Twelve patients received placebo and eight received acyclovir. If the event of clinical deterioration, patients could be removed from the study to receive acyclovir. Eighteen patients had skin lesions within 96 hours of admission to the study. Nineteen patients had malignancies. The two groups of patients were similar in age, in concomitant or preceding immunosuppressive therapy, in status of malignancy, and in presenting granulocyte and lymphocyte counts. Zoster immune globulin or plasma had been given to 50% of the placebo group but to only 25% of the acyclovir group. One patient in each group had pneumonitis at entry. Of the patients without pneumonitis at entry, five of the 11 placebo patients compared with none of the seven acyclovir patients developed pneumonitis during treatment (P = 0.054). No evidence of toxicity related to acyclovir was observed.