Varicella-zoster Virus Antibody Titers Research Articles

P402 Incidence and outcomes of herpes zoster in the ozanimod phase, 3 ulcerative colitis and relapsing multiple sclerosis clinical program

Abstract Background Patients with ulcerative colitis (UC) and patients with multiple sclerosis (MS) have an elevated risk of developing herpes zoster (HZ), caused by reactivation of latent varicella zoster virus (VZV). Increased incidence of HZ has been reported with sphingosine, 1-phosphatase (S1P) receptor modulators. This analysis examined the number of patients who failed screening due to a lack of demonstrated VZV immunity and the incidence of HZ from completed phase, 3 ozanimod clinical trials. Methods Safety results were included from True North (52-week trial) in patients with UC, and SUNBEAM (12-month trial), and RADIANCE (24-month trial) in patients with MS. All patients were required to have had a positive VZV IgG antibody status or completed VZV vaccination ≥30 days prior to randomization based on known effects of S1P modulators. Patients with a negative VZV antibody titer could choose to receive the VZV vaccination to qualify for the trial. Number of pre-screen failures because of lack of demonstrated immunity, occurrence of HZ, and association between HZ cases and lymphopenia were analyzed. Results Of, 1831 patients with UC screened for VZV immunity, 104 (5.7%) failed screening due to lack of documentation of VZV antibody or VZV vaccination ≥30 days before randomization;, 22% (23/104) subsequently received varicella vaccination and were rescreened and enrolled. Of, 3332 MS patients tested for VZV immunity, 309 (9.3%) tested negative and, 32% (98/309) of these patients were vaccinated prior to randomization. In the UC and MS trials, the incidence of HZ cases was low in ozanimod-treated patients (8 cases [1.0%] and, 5 cases [0.6%], respectively; Table, 1). All cases were distributed across a single dermatome, did not result in a complication of HZ, and were treated with oral antivirals while patients remained on ozanimod. None of the patients discontinued ozanimod because of HZ and none of the HZ cases were associated with grade, 4 lymphopenia (defined as an absolute lymphocyte count <0.2 x, 109/L). Conclusion In the ozanimod phase, 3 UC and MS trials, 5%–10% of patients screened did not have demonstrated VZV immunity;, 22%–32% of these patients received varicella vaccination, were rescreened and enrolled. The overall HZ incidence in clinical trials was low (≤1% of patients), all cases were distributed across a single dermatome, and no serious or complicated cases occurred in ozanimod-treated patients with VZV immunity. Additional studies are warranted to evaluate the incidence of HZ in clinical practice.

Varicella-zoster virus-associated meningitis, encephalitis, and myelitis with sporadic skin blisters: A case report

BACKGROUNDVaricella-zoster virus (VZV) generally causes chickenpox at first infection in childhood and then establishes latent infection in the dorsal root ganglia of the spinal cord or other nerves. Virus reactivation owing to an impaired immune system causes inflammation along spinal nerves from the affected spinal segment, leading to skin manifestations (herpes zoster). Viremia and subsequent hematogenous transmission and nerve axonal transport of the virus may lead to meningitis, encephalitis, and myelitis. One such case is described in this study.CASE SUMMARYA 64-year-old man presented with dysuria, pyrexia, and progressive disturbance in consciousness. He had signs of meningeal irritation, and cerebrospinal fluid (CSF) analysis revealed marked pleocytosis with mononuclear predominance and a CSF/serum glucose ratio of 0.64. Head magnetic resonance imaging revealed hyperintense areas in the frontal lobes. He had four isolated blisters with papules and halos on his right chest, right lumbar region, and left scapular region. Infected giant cells were detected using the Tzanck test. Degenerated epidermal cells with intranuclear inclusion bodies and ballooning degeneration were present on skin biopsy. Serum VZV antibody titers suggested previous infection, and the CSF tested positive for VZV-DNA. He developed paraplegia, decreased temperature perception in the legs, urinary retention, and fecal incontinence. The patient was diagnosed with meningitis, encephalitis, and myelitis and was treated with acyclovir for 23 days and prednisolone for 14 days. Despite gradual improvement, the urinary retention and gait disturbances persisted as sequelae.CONCLUSIONVZV reactivation should be considered in differential diagnoses of patients with sporadic blisters and unexplained central nervous system symptoms.

Phase 3, open-label, Russian, multicenter, single-arm trial to evaluate the immunogenicity of varicella vaccine (VARIVAX™) in healthy infants, children, and adolescents

ABSTRACT Varicella (chickenpox) is a common, highly contagious disease caused by primary infection with varicella zoster virus (VZV), which can result in bacterial superinfection, central nervous system complications, and hospitalization. Stage 2 of this Phase 3 open-label study (ClinicalTrials.gov identifier: NCT03843632) enrolled 100 healthy infants, children, and adolescents (12 months–6 years, n = 37; 7–12 years, n = 33; 13–17 years, n = 30) without a clinical history of varicella. Participants aged 12 months–12 years were administered 1 dose of VARIVAX™ 0.5 mL (Varicella Virus Vaccine Live [Oka/Merck]) and adolescents aged 13–17 years were administered 2 doses 6 weeks apart. For participants seronegative at baseline (VZV antibody titer <1.25 glycoprotein enzyme-linked immunosorbent assay [gpELISA] units/mL), immunogenicity was assessed by seroconversion (VZV antibody titer ≥5 gpELISA units/mL) and VZV antibody geometric mean titers 6 weeks after the final dose. For participants who were VZV seropositive at baseline (VZV antibody titer ≥1.25 gpELISA units/mL), immunogenicity was assessed by antibody titer geometric mean fold rise and percentage of participants with ≥4-fold rise in antibody titer 6 weeks after the final dose. A Vaccine Report Card was used to report solicited and unsolicited adverse events through 42 days post-vaccination. After series completion among seronegative participants across age groups (n = 74), 98.6% demonstrated seroconversion 6 weeks post-vaccination; among seropositive participants (n = 26), 65.4% had ≥4-fold rise in antibody titer 6 weeks post-vaccination. No new safety signals were observed. Administering VARIVAX to infants, children, and adolescents resulted in an acceptable immune response with a safety profile consistent with the licensed product.

Phase 3, open-label, Russian, multicenter, single-arm trial to evaluate the immunogenicity of varicella vaccine (VARIVAX™) in healthy adults

ABSTRACT Varicella (chickenpox) is a common, highly contagious disease caused by primary infection with varicella zoster virus (VZV). Adults typically experience more severe symptoms than children and have a higher risk of developing complications. Stage 1 of this Phase 3 open-label study enrolled healthy adults in Russia aged 18–75 years without a clinical history of varicella infection. Eligible participants (n = 50) were administered 2 doses of VARIVAX™ (Varicella Virus Vaccine Live [Oka/Merck]) 0.5 mL 6 weeks apart. For participants seronegative at baseline (VZV antibody titer <1.25 glycoprotein enzyme-linked immuno-sorbent assay [gpELISA] units/mL), immunogenicity was assessed by seroconversion (VZV antibody titer ≥5 gpELISA units/mL) and assessment of geometric mean titers of VZV antibody as measured by gpELISA 6 weeks after Dose 2. For VZV seropositive participants at baseline (VZV antibody titer ≥1.25 gpELISA units/mL), immunogenicity was assessed by geometric mean fold rise in antibody titer and percentage of participants with a ≥ 4-fold rise in antibody titer 6 weeks after Dose 2. A Vaccine Report Card was used to record solicited and unsolicited adverse events through 42 days post-vaccination. All participants who were seronegative (n = 26) at baseline demonstrated seroconversion 6 weeks after Dose 2. Among participants who were seropositive at baseline (n = 23), 60.9% had a ≥4-fold rise in antibody titer 6 weeks after Dose 2. Vaccination was generally well tolerated, with no new safety signals identified. Administration of 2 doses of VARIVAX in adults in Russia results in acceptable immune responses with safety data consistent with the licensed product (Clinicaltrials.gov identifier: NCT03843632).

S1639 SAFETY AND EFFICACY OF LIVE ATTENUATED VARICELLA VACCINE FOR PREVENTING VARICELLA ZOSTER VIRUS DISEASE AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION: A PROSPECTIVE SINGLE‐CENTER STUDY

Background:Varicella‐zoster virus (VZV) disease commonly occurs after allogeneic hematopoietic stem cell transplantation (allo‐HCT). Although long‐term acyclovir prophylaxis can prevent reactivation of VZV during acyclovir administration, VZV disease still remains a major problem after discontinuation of acyclovir. Thus, reconstitution of VZV‐specific T‐cell immunity may be necessary for allo‐HCT patients to prevent VZV disease completely. Vaccination against VZV has been considered as the method for accelerating VZV‐specific immune recovery. However, limited data is available on VZV vaccination after allo‐HCT.Aims:We conducted a single‐center, single‐arm, prospective study to evaluate safety and efficacy of live attenuated varicella vaccine for preventing VZV disease in adult patients who underwent allo‐HCT.Methods:Patients without active chronic GVHD, relapse and ongoing immunosuppressive therapy at 2 years after allo‐HCT were eligible for this study. We administered a single dose of live attenuated varicella vaccine (Biken, Osaka, Japan) to the enrolled patients. The primary endpoint was cumulative incidence of VZV disease after vaccination. Secondary endpoints were adverse effect of vaccine, and evaluation of VZV antibody titer and VZV specific T‐cells before and after vaccination. Immunoglobulin G (IgG) antibody titers against VZV were measured by enzyme immunoassay (EIA) using patient plasma. IgG index value of equal to or greater than 4 was considered positive. This study was approved by the institutional review boards of Jichi Medical University. Written informed consent was obtained from all patients in accordance with the Declaration of Helsinki. The study was registered at UMIN Clinical Trials Registry (UMIN000013799).Results:A total of 25 adult patients were enrolled in this study. The cumulative incidences of VZV disease at 1 and 2 years after vaccination were both 20.0% (95% confidence interval (CI), 2.7–34.2%). Six patients developed VZV disease (zoster) at a median of 224 days (range 89–874) after vaccination. No adverse events associated with varicella vaccine were observed. The median VZV IgG titers were 3.8 (range &lt;2 ‐ 82.2) before vaccination and 5.2 (range &lt;2 ‐ 56.9) at 1 month after vaccination. To predict the development of VZV disease after vaccination, we defined some cut off values of lymphocyte and IgG using the receiver‐operating characteristics curve. The lower CD4+ T‐cell count (≤468/μL) and CD4/CD8 T‐cell ratio (≤0.53) at the time of vaccination groups significantly experienced VZV disease at 2 years after vaccination (28.6% vs 0%, p = 0.036, and 44.4% vs 0%, p = 0.0020, respectively). In addition, the lower VZV IgG (≤8.1) at 1month after vaccination was also associated with higher incidence of VZV disease (29.4% vs 0% at 2 years, p = 0.062).Summary/Conclusion:The current study indicated that a single dose of live attenuated varicella vaccine was safe and effective for preventing VZV disease in adult allo‐HCT patients. However, the effect was insufficient for some patients. Therefore, additional strategies, such as the administration of at least 2 dose of varicella vaccine, may be necessary to eradicate VZV disease.

Serology indicates cytomegalovirus infection is associated with varicella‐zoster virus reactivation

Varicella-zoster virus (VZV) causes chickenpox after which the virus remains latent in neural ganglia. Subsequent reactivation episodes occur, leading mainly to subclinical detection of VZV, but also to the clinical entity herpes zoster. These reactivations are known to occur most frequently amongst immunocompromised individuals, but the incidence of herpes zoster is also known to increase with age, supposedly as a consequence of immunosenescence. Our analysis aims to explore associations between cytomegalovirus (CMV) infection and VZV reactivation by analyzing VZV-specific antibody titers as a function of age, gender, and CMV serostatus. The analysis was repeated on measles and parvovirus B19 antibody titers. At the time of the observations, measles virus circulation was virtually eliminated, whereas parvovirus B19 circulated at lower levels than VZV. Multiple linear regression analyses, using the log-transformed antibody titers, identified a positive association between ageing and VZV antibody titers suggesting that ageing increasingly stimulates VZV reactivation. CMV infection further amplified the positive association between ageing and the reactivation rate. A negative association between CMV infection and VZV antibody titers was found in young individuals, thereby supporting the hypothesis that CMV infection may have a negative effect on the number of B-cells. However, no associations between CMV infection and measles or parvovirus B19 antibody titers occurred, but ageing tended to be associated with a decrease in the antibody titer against parvovirus B19. The combined results thus suggest that both CMV-dependent and CMV-independent immunosenescence occurs. This is supported by an in-depth analysis of VZV, measles and parvovirus B19 antibody titers.

Immunogenicity and safety of a live attenuated shingles (herpes zoster) vaccine (Zostavax®) in individuals aged ≥ 70 years: A randomized study of a single dose vs. two different two-dose schedules

Disease protection provided by herpes zoster (HZ) vaccination tends to reduce as age increases. This study was designed to ascertain whether a second dose of the HZ vaccine, Zostavax®, would increase varicella zoster virus (VZV)-specific immune response among individuals aged ≥ 70 y. Individuals aged ≥ 70 y were randomized to receive HZ vaccine in one of three schedules: a single dose (0.65 mL), two doses at 0 and 1 mo, or two doses at 0 and 3 mo. VZV antibody titers were measured at baseline, 4 weeks after each vaccine dose, and 12 mo after the last dose. In total, 759 participants (mean age 76.1 y) were randomized to receive vaccination. Antibody responses were similar after a single dose or two doses of HZ vaccine [post-dose 2/post-dose 1 geometric mean titer (GMT) ratios for the 1-mo or 3-mo schedules were 1.11, 95% confidence interval (CI) 1.02–1.22 and 0.78, 95% CI 0.73–0.85], respectively). The 12-mo post-dose 2/12-mo post-dose 1 GMT ratio was similar for the 1-mo schedule and for the 3-mo schedule (1.06, 95% CI 0.96–1.17 and 1.08, 95% CI 0.98–1.19, respectively). Similar immune responses were observed in participants aged 70–79 y and those aged ≥ 80 y. HZ vaccine was generally well tolerated, with no evidence of increased adverse event incidence after the second dose with either schedule. Compared with a single-dose regimen, two-dose vaccination did not increase VZV antibody responses among individuals aged ≥ 70 y. Antibody persistence after 12 mo was similar with all three schedules.

Varicella Zoster Virus Disease After Pediatric Living Donor Liver Transplantation: Is It Serious?

ObjectivesThe aim of this study was to evaluate patients who developed varicella zoster virus (VZV) disease after pediatric living donor liver transplantation (PLDLT). MethodsTwo hundred fifty-five patients who underwent PLDLT between 1995 and 2010 were included in this study. Pretransplantation vaccination of VZV was performed for all recipients except emergency PLDLTs. Posttransplantation VZV vaccination was administered to the patients with a low VZV antibody titer 2 years or more after transplantation. The clinical course and outcomes of VZV disease in cases were reviewed with the transplant database and hospital medical records. ResultsSixty-three patients developed VZV disease (chicken pox in 61, herpes zoster in 2) at a median onset of 36 months after PLDLT and at a median age of 4 years old, with a cumulative incidence of 25%. All chicken pox occurred in VZV antibody-negative patients. The onset of herpes zoster in the two patients occurred within 3 months after PLDLT; in addition, these patients were VZV antibody-positive patients. The clinical presentations of most patients were not serious and there were no disseminated infections. Although only 3 patients (5%) were hospitalized, the other 60 patients (95%) all showed a good response to oral antiviral therapy. ConclusionsAlthough VZV disease is an infectious disease with a high morbidity rate after PLDLT, it can normally be successfully managed on an outpatient basis at home. Pre- and posttransplantation vaccinations are effective for delaying the onset of chicken pox after PLDLT and to prevent it from developing into a serious illness.

Immunogenicity and safety of ZOSTAVAX® approaching expiry potency in individuals aged ≥50 years

Background: Age is a major risk factor for herpes zoster (HZ) and its potential long-term complication post-herpetic neuralgia (PHN). Due to the significant burden of HZ and PHN on patients’ quality of life, it is vital that effective and well-tolerated vaccines are available to prevent HZ in older adults. ZOSTAVAX® vaccine was developed to prevent HZ and PHN in individuals ≥50 years (y) of age, and its clinical efficacy and safety have been demonstrated.Aims and Methods: This phase 4, open-label, multicenter study was undertaken to assess the immunogenicity and safety of a single dose of ZOSTAVAX (refrigerator-stable formulation) given within 6 mo of its expiry date in individuals ≥50 y of age. The geometric mean fold rise (GMFR) from pre-vaccination to 4 weeks post-vaccination in varicella zoster virus (VZV) antibody titers was calculated. An acceptable antibody response was defined as a lower 95% confidence interval (CI) of GMFR >1.4. Solicited and unsolicited injection-site reactions and systemic adverse events were recorded.Results: The GMFR in VZV antibody titers was 3.1 (95% CI: 2.6, 3.8), satisfying the criterion for an acceptable VZV antibody response to ZOSTAVAX (minimum requirement: 1.4 GMFR). An acceptable rise in VZV antibody titers was observed in individuals of 50–59 y of age (GMFR 3.9; 95% CI: 2.9, 5.1) and in those ≥60 y of age (GMFR 2.5; 95% CI: 1.9, 3.2). ZOSTAVAX was well tolerated; no serious adverse events were reported.Conclusion: ZOSTAVAX elicits an acceptable immune response in immunocompetent individuals ≥50 y of age when stored as directed and administered during the 6 mo prior to expiration.

Comparison of the Safety and Immunogenicity of a Refrigerator-Stable Versus a Frozen Formulation of ProQuad (Measles, Mumps, Rubella, and Varicella Virus Vaccine Live)

A refrigerator-stable formulation of ProQuad has been developed to expand the utility of ProQuad to areas in which maintenance of a frozen cold chain (-15 degrees C or colder) during storage and transport may not be feasible. The objective of this study was to demonstrate that the immunogenicity and safety profiles of a refrigerator-stable formulation of ProQuad are similar to the recently licensed frozen formulation. In this double-blind, randomized, multicenter study, healthy 12- to 23-month-old children with negative vaccination and clinical histories for measles, mumps, rubella, varicella, and zoster were vaccinated with either the refrigerator-stable formulation of ProQuad (N = 1006) or the frozen formulation of ProQuad (N = 513). Patients were followed for 42 days after vaccination for adverse experiences. Immunogenicity was evaluated 6 weeks after vaccination. The refrigerator-stable formulation of ProQuad was generally well tolerated. The incidence of adverse experiences was similar between groups. No vaccine-related serious adverse experiences were reported. For both groups, the response rate was > or = 97.7% for measles, mumps, and rubella, and the percentage of patients with a varicella zoster virus antibody titer of > or = 5 U/mL glycoprotein antigen-based enzyme-linked immunosorbent assay after vaccination was > or = 88.8%. The geometric mean titers for all antigens were numerically slightly higher in patients who received the refrigerator-stable formulation. The refrigerator-stable formulation of ProQuad is generally well tolerated, highly immunogenic, and noninferior in terms of postvaccination antibody responses. This refrigerator-stable formulation may improve ease of vaccine administration, increase use of the vaccine throughout the world because of its improved storage conditions, and replace the frozen formulation of ProQuad or any dose of M-M-RII and Varivax in routine practice.

Safety and immunogenicity of a zoster vaccine in varicella-zoster virus seronegative and low-seropositive healthy adults

Objective To evaluate immunogenicity and tolerability of a live attenuated zoster vaccine in varicella-zoster virus (VZV) seronegative or low-seropositive adults ≥30 years of age. Study design Double-blind, placebo-controlled, randomized, multicenter study. Subjects were enrolled in two stages by prescreened serostatus. Subjects with a low VZV antibody titer (≤5 gpELISA units/mL) were enrolled in Stage 1. Subjects with undetecable VZV antibodies and no safety issues identified during Stage 1 were enrolled in Stage 2. All enrolled subjects were randomized 4:1 to receive one dose (∼50,000 PFU) of zoster vaccine or placebo and were followed for safety for 42 days postvaccination. Primary objectives/hypotheses: (1) no vaccine-related serious adverse experiences (AE); (2) ≤1 laboratory-confirmed varicella-like rash with >50 lesions within 42 days postvaccination. Secondary objective: summarize the VZV antibody response postvaccination. Results Twenty-one subjects (age 27 to 69 years; median 34) enrolled (1148 prescreened); 18 (including 4 seronegative subjects) received vaccine and 3 (including 1 seronegative subject) received placebo. Twenty subjects completed the study; one subject withdrew for reasons unrelated to safety. No serious vaccine-related AE or laboratory-confirmed varicella-like rashes with >50 lesions were reported. In the zoster vaccine group, all 4 of the initially seronegative subjects (age 32 to 36 years; median 33.5) seroconverted and 6 of the 13 (46.2%) initially seropositive subjects had a ≥4-fold rise in VZV-specific antibody titer at 6 weeks postvaccination. Conclusions The zoster vaccine appears to be immunogenic and generally well tolerated in healthy adults ≥30 years of age, regardless of initial VZV antibody serostatus.

Transition of Humoral Immunity and Clinical VZV Reactivation in Hematopoietic Stem Cell Transplantation Recipients.

Reactivation of varicella-zoster virus (VZV) is common among recipients of hematopoietic stem cell trasnplantation (HSCT). In this setting, VZV infection can occur frequently as localized zoster (shingles) and sometimes as disseminated varicella (chickenpox) with or without visceral involvement, which results in a high mortality rate. Previous studies revealed that VZV-specific memory T cells play a crucial role in suppressing reactivation. Although varicella zoster immunoglobulin is used as a prophylactic and treatment modality in some contries, the role of humoral immunity against VZV infection has been poorly evaluated. The aim of the study was to identify the relationship between quantitative transition of VZV antibody titers and clinical manifestation of VZV infection in HSCT recipients. Thirteen patients with VZV infection after HSCT (7 males, 6 females; age: 21–65 years, median age: 35 years) were enrolled. Eleven patients (allo, 7; auto, 4) suffered localized zoster. Two patients (both allo) suffered systemic varicella with visceral involvement (1 with acute abdomen and 1 with interstitial pneumonia). All patients were treated with acyclovir. Seven patients who had been followed for at least 3 years after HSCT without clinical VZV infection were studied as control subjects (4 males, 3 females; age: 16–40 years, median age: 28 years; allo, 6; auto, 1). We retrospectively studied transition of anti-VZV-IgG titer by the IAHA and gpELISA method (before and at 3, 6, 12, 24, 36 months after HSCT) and VZV-DNA by realtime PCR during clinical VZV infection (onset and paired serum) using cryopreserved serum samples. All patients were seropositive for VZV before HSCT. One of the patients (the most severe case) had become seronegative before systemic varicella developed. However, VZV infections in the other 12 patients occurred despite the persistent existence of anti-VZV (IAHA:x8 to >x256; median x32). There are no statistically significant differences between anti-VZV titers in the 13 patients with VZV infection and those in the 7 controls at each time point. Acceleration of the titer (>x4) was not observed in any of the 9 recipients with VZV infection within the first 6 months after HSCT but was observed in 3 of 4 recipients with VZV infection after 6 months (Figure 1). Four available samples at onset of VZV infection (varicella, 2; zoster, 2) were all positive for VZV-DNA (94.4 to 12173.3 copies /ml serum) by realtime PCR, whereas VZV was undetectable in all paired sera (2 to 5 weeks after onset). Pre-existing anti-VZV titer (gpELISA) and serum viral load were inversely correlated (Figure 2). In HSCT recipients, pre-existing antibody does not prevent development of VZV reactivation but may contribute to decreased viral load, resulting in a mild clinical course. Despite the localized clinical feature of zoster, VZV was detected in serum samples from zoster patients. Clinicians should be aware of the risk of airborne transmission of VZV from HSCT recipients with either varicella or zoster. [Display omitted]

Dose-Response Study of a Quadrivalent Measles, Mumps, Rubella and Varicella Vaccine in Healthy Children

A combined measles, mumps, rubella and varicella (MMRV) vaccine would facilitate universal immunization against 4 diseases by decreasing the number of injections and thus enhancing compliance and coverage rates. If a second dose of varicella vaccine were to be recommended, MMRV could be used to administer a routine second dose of M-M-RII with the added advantage of boosting varicella-zoster virus (VZV) antibody titers. Subjects 12-23 months of age received a single injection of 1 of 3 lots of an MMRV vaccine (ProQuad) containing high, middle or low VZV potency, or VARIVAX given concomitantly with M-M-RII. Recipients of MMRV received a second injection of MMRV approximately 90 days later. We enrolled 1559 subjects in the study. Antibody response rates to VZV 6 weeks after 1 injection of high potency MMRV (88.6%) or 2 injections of MMRV of any varicella potency (99.7-100%) were similar to the response rates after concomitant administration of M-M-RII and VARIVAX (93.1%). The second injection of MMRV boosted VZV antibody titers. Antibody responses to measles, mumps and rubella were >or=98%, similar to the control, after 1 or 2 injections of MMRV. MMRV was generally well-tolerated during the 42 days after vaccination. One injection of high potency MMRV resulted in antibody responses to the 4 vaccine components equivalent to those found after concomitant administration of M-M-RII and VARIVAX. A second injection of MMRV resulted in a significant boost in VZV antibody. This boost may translate into enhanced immunogenicity against varicella, which is known to correlate with increased protection.

Varicella zoster virus antibody titers after intravenous zoster immune globulin in neonates, and the safety of this preparation

1) To assess the safety of intravenous varicella zoster virus hyperimmune globulin G (IV-VZVIG) in neonates; 2) measure varicella zoster virus-specific IgG antibody (VZVIG) changes in newborn IV-VZVIG recipients. Eighteen neonatal intensive care unit (NICU) neonates with varicella exposure were given 1 ml/kg (43 International Units (IU)/kg) Varitect IV-VZVIG. Serum VZVIG titers were assayed in neonatal recipients 0, 1, 7, 14, 21, 28, and 35 d after IV-VZVIG. Also, serum samples for VZV-IgM antibody determinations were obtained at 4 wk post-infusion. No varicella developed in the 18 infants. Infusion of 1 ml/kg (43 IU/kg) IV-VZVIG was generally safe. The IV-VZVIG dose resulted in seroconversion of a non-immune newborn. Five infants had low basal VZVIG titers, and two of them had a 0.6-log10 increase at 24 h post-infusion. Neonatal VZVIG titers (mean+/-SEM in log(10)) before IV-VZVIG and after by 1, 7, 14, 21, 28, and 35 d were 2.22+/-0.15, 2.17+/-0.17, 2.02+/-0.12, 0.87+/-0.2, 1.09+/-0.19, 2.33+/-0.07, and 2.16+/-0.1, respectively. One ml/kg (43 IU/kg) IV-VZVIG was generally safe. Our neonatal mean VZV-immune status did not significantly increase after the 1 ml/kg (43 IU/kg) IV-VZVIG dose, although no varicella developed and it caused a VZV-specific seroconversion.

Varicella zoster virus antibody titers after intravenous zoster immune globulin in neonates, and the safety of this preparation

Varicella zoster virus antibody titers after intravenous zoster immune globulin in neonates, and the safety of this preparation

Successful Vaccination Against Varicella Zoster Virus Prior to Kidney Transplantation

Background In recent years we have observed a number of severe complications of primary varicella-zoster virus (VZV) infections after adult kidney transplantation. We questioned how many patients on the waiting list for kidney transplantation had not been protected against VZV and whether patients with renal insufficiency would be able to develop a specific immune response upon VZV vaccination. Methods We examined the VZV antibody titer of 280 patients on the kidney transplant waiting list. Seronegative kidney transplant candidates were vaccinated twice with a live attenuated varicella vaccine at an interval of 6 weeks. Conclusions Approximately 3% of patients on the waiting list were seronegative for VZV. Vaccination induced no side effects and resulted in a positive serologic response in most patients.

SUCCESSFUL VACCINATION AGAINST VARICELLA ZOSTER VIRUS PRIOR TO KIDNEY TRANSPLANTATION

Background: In recent years we have observed a number of severe complications of primary varicella-zoster virus (VZV) infections after adult kidney transplantation. We questioned how many patients on the waiting list for kidney transplantation had not been protected against VZV and whether patients with renal insufficiency would be able to develop a specific immune response upon VZV vaccination. Methods: We examined the VZV antibody titer of 280 patients on the kidney transplant waiting list. Seronegative kidney transplant candidates were vaccinated twice with a live attenuated varicella vaccine at an interval of 6 weeks. Conclusions: Approximately 3% of patients on the waiting list were seronegative for VZV. Vaccination induced no side effects and resulted in a positive serologic response in most patients.

Immunization of the elderly to boost immunity against varicella-zoster virus (VZV) as assessed by VZV skin test reaction.

The utility of the VZV skin test in detecting individual susceptibility to varicella and zoster was determined. Its specificity particularly with regard to herpes simplex was also established. The VZV skin test was negative or weakly positive during the early stage of herpes zoster, and strongly positive during recovery from that disease. A small-scale clinical trial to immunize elderly individuals has been performed for the purpose of preventing herpes zoster, and, perhaps, severe post-herpetic neuralgia as well. Sixty individuals > or = 50 years old were screened for VZV antibodies by IAHA test and were given a VZV skin test for cell-mediated immunity. All were seropositive, but eight were skin-test negative. Thirty-seven individuals including the eight with negative skin tests were immunized with one dose of varicella vaccine (3.0 x 10(4) PFU/dose). After 5-7 weeks, the skin test reaction showed increased positivity, with a change in score from (-) to (+, ++) in 7/8 subjects, from (+) to (++, +++) in 3/5 subjects, and from (++) to (+++) in 6/10 subjects. Enhancement of the VZV antibody titer (defined as twofold or greater) was observed in all 15 vaccine recipients with a prevaccination titer of < or = 1:16, and in 19 of 24 subjects with a prevaccination titer of > or = 1:32. These results indicate that giving live varicella vaccine with a high viral titer can induce a good boost immunity particularly cell-mediated immunity to VZV in the elderly.

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

Two Cases of Peripheral Facial Paralysis Associated with Varicella

Facial paralysis caused by chickinpox are rare. Two cases of facial paralysis associated with varicella were described.First case, a 5-year-old girl, complained of immobility of right facial muscle on Feb. 6, 1979. Three days later, she developed typical varicella. Laboratory studies revealed no abnormalities except for an elevated anti varicella-zoster virus (VZV) antibody levels in the serum. Anti VZV antibody titers were measured by immune adherence hemagglutination test (IAHA). The serum IAHA titers for VZV were 1:128 (Feb. 14) and 1:128 (March 5). Complete recovery occured five weeks after the onset.Second case, a 5-year-old boy, had a skin rash and diagnosed as varicella on April 5, 1979. On May 17, he noticed a weakness of the right facial muscle. No other neurological abnormalities were observed. About two weeks later, mumps occured. The serum IAHA titers for VZV were 1:64 (May 23) and 1:128 (June 18) and the mumps virus antibody titers were 1:<2 (May 23) and 1:64 (June 18). The facial palsy completely recovered after six weeks.