Safety and tolerability of a high-potency zoster vaccine in adults >/= 50 or years of age. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. Safety, tolerability, and immunogenicity after 1 and 2 doses of zoster vaccine in healthy adults ≥60 years of age. Safety, tolerability, and immunogenicity of zoster vaccine in subjects with a history of herpes zoster. Early reconstitution of immunity and decreased severity of herpes zoster in bone marrow transplant recipients immunized with inactivated varicella vaccine. Safety and tolerability of zoster vaccine in adults ≥60 years old. Use of an inactivated varicella vaccine in recipients of hematopoietic-cell transplants. A dose-response study of a live attenuated varicella-zoster virus (Oka strain) vaccine administered to adults 55 years of age and older.
Herpes zoster (HZ) incidence rises with age, especially after 50 years of age, probably due to waning varicella-zoster virus (VZV)-specific immunity. The Shingles Prevention Study [Oxman MN, Levin MJ, Johnson GR, Schmader KE, Straus SE, Gelb LD, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults, N Engl J Med 2005;352:2271-84], enrolled people >/= 60 or years of age and showed that zoster vaccine prevents HZ and postherpetic neuralgia (PHN), presumably through boosting VZV-specific immunity. This study of people >/= 50 or years of age compared the safety and tolerability of two zoster vaccine potencies.
                Adults >/= 50 or years old enrolled in a randomized, double-blind, multicenter study to compare the safety and tolerability of one dose of two zoster vaccine potencies, approximately 58,000 and approximately 207,000 plaque-forming units/dose. Adverse experiences (AEs) were recorded on a standardized Vaccination Report Card for 42 days postvaccination. For assessment of injection-site AEs, clinically acceptable tolerability was predefined based on experience with PNEUMOVAX 23, a licensed vaccine recommended for use in older people.
                Six hundred and ninety-eight subjects (age 50-90 years, median 64 years) were enrolled. No serious vaccine-related AEs were reported. Similar AE rates were observed in the higher and lower potency groups (overall systemic AEs: 37.5 and 39.3%, vaccine-related systemic AEs: 10.9 and 13.2%, injection-site AEs: 63.0 and 59.8%). Rates for a combined endpoint of moderate or severe injection-site pain/tenderness/soreness and swelling were 17.2% (95% CI 13.9, 21.0) and 9.0% (95% CI 5.6, 13.4), respectively. Most combined endpoint events were reported as moderate in intensity.
                Both vaccine potencies were generally well tolerated in this study of people > or years of age. Although rates of some moderate or severe injection-site AEs were greater in the higher potency group, all rates met the prespecified criteria for clinically acceptable tolerability. The incidence and severity of herpes zoster and postherpetic neuralgia increase with age in association with a progressive decline in cell-mediated immunity to varicella-zoster virus (VZV). We tested the hypothesis that vaccination against VZV would decrease the incidence, severity, or both of herpes zoster and postherpetic neuralgia among older adults.
                We enrolled 38,546 adults 60 years of age or older in a randomized, double-blind, placebo-controlled trial of an investigational live attenuated Oka/Merck VZV vaccine ("zoster vaccine"). Herpes zoster was diagnosed according to clinical and laboratory criteria. The pain and discomfort associated with herpes zoster were measured repeatedly for six months. The primary end point was the burden of illness due to herpes zoster, a measure affected by the incidence, severity, and duration of the associated pain and discomfort. The secondary end point was the incidence of postherpetic neuralgia.
                More than 95 percent of the subjects continued in the study to its completion, with a median of 3.12 years of surveillance for herpes zoster. A total of 957 confirmed cases of herpes zoster (315 among vaccine recipients and 642 among placebo recipients) and 107 cases of postherpetic neuralgia (27 among vaccine recipients and 80 among placebo recipients) were included in the efficacy analysis. The use of the zoster vaccine reduced the burden of illness due to herpes zoster by 61.1 percent (P<0.001), reduced the incidence of postherpetic neuralgia by 66.5 percent (P<0.001), and reduced the incidence of herpes zoster by 51.3 percent (P<0.001). Reactions at the injection site were more frequent among vaccine recipients but were generally mild.
                The zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults.
                Copyright 2005 Massachusetts Medical Society. Incidence and severity of herpes zoster (HZ) and postherpetic neuralgia increase with age, associated with age-related decrease in immunity to varicella-zoster virus (VZV). One dose of zoster vaccine (ZV) has demonstrated substantial protection against HZ; this study examined impact of a second dose of ZV.
                Randomized, double-blind, multicenter study with 210 subjects ≥60 years old compared immunity and safety profiles after one and two doses of ZV, separated by 6 weeks, vs. placebo. Immunogenicity was evaluated using VZV interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISPOT) assay and VZV glycoprotein enzyme-linked immunosorbent antibody (gpELISA) assay. Adverse experiences (AEs) were recorded on a standardized Vaccination Report Card.
                No serious vaccine-related AEs occurred. VZV IFN-γ ELISPOT geometric mean count (GMC) of spot-forming cells per 10(6) peripheral blood mononuclear cells increased in the ZV group from 16.9 prevaccination to 49.5 and 32.8 at 2 and 6 weeks postdose 1, respectively. Two weeks, 6 weeks and 6 months postdose 2, GMC was 44.3, 42.9, and 36.5, respectively. GMC in the placebo group did not change during the study. The peak ELISPOT response occurred ∼2 weeks after each ZV dose. The gpELISA geometric mean titers (GMTs) in the ZV group were higher than in the placebo group at 6 weeks after each dose. Correlation between the IFN-γ ELISPOT and gpELISA assays was poor.
                ZV was generally well-tolerated and immunogenic in adults ≥60 years old. A second dose of ZV was generally safe, but did not boost VZV-specific immunity beyond levels achieved postdose 1.
                Copyright © 2011 Elsevier Ltd. All rights reserved. Prior clinical studies of zoster vaccine enrolled subjects without a history of herpes zoster (HZ), so there are limited data on safety and immunogenicity in vaccinees with a prior history of HZ. This study was conducted to evaluate the safety and immunogenicity of zoster vaccine recipients who had a prior episode of HZ.
                A total of 101 subjects > or = 50 years of age with a prior history of HZ were enrolled. They were stratified by number of years since their HZ (5 to 9 years and > or = 10 years, in an approximate 2:1 ratio), and randomized 1:1 to one of two vaccination groups. On day 1, Group I was administered zoster vaccine and Group II received placebo. At week 4, Group I received placebo and Group II received zoster vaccine. Subjects were followed for adverse experiences (AEs), exposure to varicella or HZ, and development of any varicella/varicella-like or HZ/HZ-like rashes, for 28 days after each injection. Blood samples were obtained prior to study injection on day 1 and week 4, and at week 8. Serum was assessed for varicella-zoster virus (VZV) antibody concentration by glycoprotein enzyme-linked immunosorbent assay.
                No serious AEs were reported within the 28-day safety follow-up period following any vaccination. Although a higher percentage of subjects reported injection-site AEs after receiving zoster vaccine than did placebo recipients, the proportion of subjects reporting systemic clinical AEs was similar in both groups. Zoster vaccine induced a VZV antibody response at 4 weeks post-vaccination. The estimated geometric mean titer (GMT) ratio (vaccine/placebo) was 2.07 (95% CI: 1.48, 2.88). The geometric mean fold-rise (GMFR) from prevaccination to week 4 post-vaccination was 2.1 in zoster vaccine recipients, versus 1.0 in placebo recipients.
                In HZ history-positive adults > or = 50 years of age, zoster vaccine: (1) was well tolerated; and (2) significantly boosted the level of VZV antibody from baseline to 4 weeks post-vaccination as measured by GMT and GMFR. These data support the Advisory Committee on Immunization Practices' recommendation for routine zoster vaccination for all immunocompetent persons >/=60 years of age irrespective of HZ history.
                Copyright 2010 Elsevier Ltd. All rights reserved. Varicella-zoster virus (VZV) causes herpes zoster after bone marrow transplantation (BMT). The immunogenicity of heat-inactivated varicella vaccine and effects on VZV pathogenesis were evaluated in 75 BMT patients randomized to receive vaccine or no intervention. Among 14 patients given a single dose at 1 month after transplantation, the mean (+/-SE) stimulation index (SI) was 12.20 +/- 3.13 compared with 4.83 +/- 2.74 (P = .036) in 14 unvaccinated patients, but clinical disease was not altered. Among 24 patients vaccinated at 1, 2, and 3 months, mean SI was 8.43 +/- 3.89 versus 2.00 +/- 0.33 (P = .014) in 23 unvaccinated patients at 4 months and 8.56 +/- 2.81 versus 5.30 +/- 2.47 (P = .043) at 5 months. Disease severity associated with VZV reactivation was decreased dramatically in vaccinees given three doses; severity scores were 6.4 +/- 1.0 versus 11.8 +/- 1.1 (P = .007). This experience with varicella vaccine in BMT patients is the first evidence that active immunization can reduce morbidity due to herpesvirus reactivation in high-risk populations. To evaluate the general safety of zoster vaccine (ZV) in adults ≥60 years old.
                Subjects were enrolled in a 1:1 ratio to receive 1 dose of ZV or placebo. Subjects were followed for serious adverse experiences (SAEs) for 42 days (primary follow-up period) and 182 days (secondary follow-up period) postvaccination. Relative-risks (ZV/placebo) for SAEs during both safety periods were calculated. Study period: 17-Sep‑2007 to 09-Jan-2009.
                Overall, 5,983 subjects received ZV and 5,997 received placebo. Within the primary 42-day follow-up period, 84 ZV subjects and 67 placebo subjects reported SAEs. The estimated risk of SAEs within 42 days was 1.41% for ZV versus 1.12% for placebo, with a relative-risk of 1.26 (95% CI 0.91,1.73); indicating no statistically significant difference between groups, meeting the pre-specified success criterion. During the 182-day follow-up period, 340 ZV subjects and 300 placebo subjects reported SAEs. The estimated risk of SAEs within 182 days was 5.68% for ZV versus 5.01% for placebo, with a relative-risk of 1.13 (95% CI 0.98,1.32), indicating no statistically significant difference between groups. Two subjects in the ZV group reported SAEs deemed by the investigator to be vaccine-related (uveitis and sciatica; onset Day 5 and 4, respectively). One subject in the placebo group reported a SAE deemed by the investigator to be vaccine-related (lumbar radiculopathy; onset Day 51). There were 24 fatal SAEs in the ZV group and 17 in the placebo group (relative risk = 1.41; CI: 0.77, 2.60); 6 and 5, respectively, with SAE onset during the primary 42-day follow-up period. No deaths were deemed vaccine-related.
                ZV and placebo groups had similar safety profiles in terms of SAEs during the primary (Day 1 to 42) and secondary (Day 1 to 182) follow-up periods. The reactivation of varicella-zoster virus from latency causes zoster and is common among recipients of hematopoietic-cell transplants.
                We randomly assigned patients who were scheduled to undergo autologous hematopoietic-cell transplantation for non-Hodgkin's or Hodgkin's lymphoma to receive varicella vaccine or no vaccine. Heat-inactivated, live attenuated varicella vaccine was given within 30 days before transplantation and 30, 60, and 90 days after transplantation. The patients were monitored for zoster and for immunity against varicella-zoster virus for 12 months.
                Of the 119 patients enrolled, 111 received a transplant. Zoster developed in 7 of 53 vaccinated patients (13 percent) and in 19 of 58 unvaccinated patients (33 percent) (P=0.01). After two patients in whom zoster developed before transplantation were excluded, the respective rates were 13 percent and 30 percent (P=0.02). In vitro CD4 T-cell proliferation in response to varicella-zoster virus (expressed as the mean stimulation index) was greater in patients who received the vaccine than in those who did not at 90 days, after three doses (P=0.04); at 120 days, after all four doses (P<0.001); at 6 months (P=0.004); and at 12 months (P=0.02). The risk of zoster was reduced for each unit increase in the stimulation index above 1.6; a stimulation index above 5.0 correlated with greater than 93 percent protection. Induration, erythema, or local pain at the injection site was observed in association with 10 percent of the doses.
                Inactivated varicella vaccine given before hematopoietic-cell transplantation and during the first 90 days thereafter reduces the risk of zoster. The protection correlates with reconstitution of CD4 T-cell immunity against varicella-zoster virus. Decreased cell-mediated immune (CMI) response to varicella-zoster virus (VZV) is correlated with an increased risk of reactivation of latent virus from dorsal root sites, leading to herpes zoster. The cell-mediated and humoral immunogenicity of three concentrations (3200, 8500, and 41,650 pfu/dose) of a live attenuated VZV vaccine (Oka strain; VZV/Oka) was compared with a control pneumococcal polysaccharide vaccine in 200 healthy adults who were > or = 55 years old. Six weeks after vaccination, the VZV-specific CMI response (as measured by stimulation index values and precursor cell frequencies) was enhanced in all VZV/Oka vaccine groups compared with the control group (for all VZV/Oka groups combined vs. controls, tested with VZV crude antigen: stimulation index, P < .001; precursor cell frequency, P < .001). Geometric mean titers of anti-VZV antibodies increased in all VZV/Oka vaccine groups but remained unchanged in the control vaccine group. No dose effect of VZV/Oka vaccine was observed for CMI or humoral responses.
Herpes zoster vaccine is effective in preventing herpes zoster disease. Although vaccine benefits are larger in the younger age group (60 to 69 years), this is also the age group with more adverse events. In general, zoster vaccine is well tolerated; it produces few systemic adverse events and injection site adverse effects of mild to moderate intensity.