Live Attenuated Varicella-zoster Virus Vaccine Research Articles

Evaluation of VZV‐specific cell‐mediated immunity in adults infected with HIV‐1 by using a simple IFN‐γ release assay

The development of herpes zoster is associated with reduced varicella zoster virus (VZV)-specific cell-mediated immune (CMI) reactions. In this study, VZV-specific CMI reactions in 42 anti-VZV-IgG antibody-positive adults infected with HIV-1 were evaluated by measuring the IFN-γ production levels in whole blood in response to stimulation with ultraviolet light-inactivated live attenuated VZV vaccine. The median VZV-specific IFN-γ production level in all patients was 63 pg/ml. Antiretroviral therapy (ART)-naïve patients with an AIDS-defining illness (HIV classification category C) had significantly lower IFN-γ production than ART-naïve patients in categories A and B and patients receiving ART (P=0.0194 and P=0.0046, respectively). IFN-γ production increased significantly in patients within 1 month of the onset of recurrent VZV disease and at more than 1 year from onset, compared with patients who had never had recurrent VZV disease (P=0.0396 and P=0.0484, respectively). In multivariate analyses, category C and history of recurrent VZV disease were significant factors affecting IFN-γ production. Levels of IFN-γ were measured before and after ART in seven ART-naïve patients with no history of recurrent VZV disease, and no significant changes were observed. The results indicate that VZV-specific CMI reactions were reduced in patients with an AIDS-defining illness and enhanced in patients with a history of recurrent VZV disease, but not enhanced by ART alone. Vaccination may be necessary to inhibit the development of herpes zoster in patients receiving ART; this IFN-γ releasing assay is one useful method for evaluating VZV-specific CMI reactions in clinical settings.

Cost-effectiveness of vaccination of the elderly against herpes zoster in The Netherlands

BackgroundEach year a substantial number of Dutch elderly suffers from herpes zoster (HZ), caused by the reactivation of the varicella zoster virus (VZV). A potential complication of HZ is postherpetic neuralgia (PHN) which results in a prolonged loss of quality of life. A large randomized clinical trial, labelled the Shingles Prevention study (SPS), demonstrated that a live attenuated VZV vaccine can reduce the incidence of HZ and PHN. ObjectiveWe aimed to estimate the incremental cost-effectiveness ratio (ICER) of vaccination of the elderly against HZ versus no such vaccination in The Netherlands. MethodsA cohort model was developed to compare the costs and effects in a vaccinated and a non-vaccinated age- and gender-stratified cohort of immune-competent elderly. Vaccination age was varied from 60 to 75 years. Data from published literature such as the SPS were used for transition probabilities. The study was performed from the societal as well as the health care payer's perspective and results were expressed in euros per quality-adjusted life year (QALY) gained. ResultsIn the base case, we estimated that vaccination of a cohort of 100,000 60-year-olds would prevent 4136 cases of HZ, 305 cases of PHN resulting in a QALY-gain of 209. From the societal perspective, a total of €1.9 million was saved and the ICER was €35,555 per QALY gained when a vaccine price of €87 was used. Vaccination of women resulted in a lower ICER than vaccination of men (€33,258 vs. €40,984 per QALY gained). The vaccination age with the most favourable ICER was 70 years (€29,664 per QALY gained). Parameters with a major impact on the ICER were the vaccine price and HZ incidence rates. In addition, the model was sensitive to utility of mild pain, vaccine efficacy at the moment of uptake and the duration of protection induced by the vaccine. ConclusionVaccination against HZ might be cost-effective for ages ranging from 60 to 75 when a threshold of €50,000 per QALY gained would be used, at €20,000 per QALY this might not be the case. Additional information on the duration of vaccine-protection is needed to further optimize cost-effectiveness estimations.

A Phase 1/2 Clinical Trial Evaluating Safety and Immunogenicity of a Varicella Zoster Glycoprotein E Subunit Vaccine Candidate in Young and Older Adults

An adjuvanted recombinant varicella zoster virus (VZV) subunit vaccine is being developed for the prevention of herpes zoster and its complications. In a phase I/II, open-label, randomized, parallel-group study, older adults (50-70 years) received 2 doses 2 months apart of an adjuvanted recombinant glycoprotein E vaccine (HZ/su; n = 45), a live attenuated Oka strain VZV vaccine (OKA; n = 45), or HZ/su and OKA administered concomitantly (n = 45). To evaluate safety prior to administration in older adults, young adults (18-30 years) were vaccinated with 2 doses 2 months apart of HZ/su (n = 10) or OKA (n = 10). Safety and immunogenicity were assessed up to 42 months for older adults immunized with HZ/su and up to 12 months for all others. Few grade 3 events and no severe adverse events were reported. Fatigue, myalgia, headache, and injection site pain were the most common solicited reactions for HZ/su and occurred more frequently than with OKA. CD4(+) T-cell and humoral immune responses were much higher with HZ/su than with OKA and remained elevated until 42 months. Addition of OKA to HZ/su did not increase immunogenicity. In this study, HZ/su adjuvanted subunit vaccine was well tolerated and more immunogenic than a live attenuated VZV vaccine. Clinical Trial registration. NCT00492648 and NCT00492648.

Interferon-γ release assay: A simple method for detection of varicella-zoster virus-specific cell-mediated immunity

Herpes zoster is closely related to decreased varicella-zoster virus (VZV)-specific cell-mediated immunity. We validated a new assay for measuring VZV-specific immunity. We cultured the whole blood of healthy subjects with live attenuated VZV vaccine. Cultured supernatants were harvested at 24-h intervals and assayed for interferon-gamma (IFN-γ) by an enzyme-linked immunosorbent assay (ELISA). The 48-h culture was suitable for estimating IFN-γ release. IFN-γ production was stable after standing for at least 4 h at room temperature. IFN-γ production was observed in whole blood from subjects with recent VZV infection, but not in blood from subjects naïve to the virus. Thus, the IFN-γ release assay may be useful as a new surrogate assay for measuring VZV-specific immunity.

Herpes zoster und postherpetische Neuralgie – Vorbeugung durch Impfung?

Herpes zoster is caused by reactivation of latent varicella-zoster virus (VZV), which had remained latent in the dorsal root or cranial nerve ganglia since the primary infection. The risk of developing zoster increases significantly with age, the vast majority of zoster cases occuring in persons over 50 years. The most frequent and debilitating complication of zoster in immunocompetent patients is postherpetic neuralgia (PHN). In the absence of antiviral therapy, clinical studies have found up to 30 - 45 % of persons over 60 years of age to experience pain persisting for more than 6 months. Systemic antiviral therapy is able to shorten the healing process of acute zoster and to prevent or alleviate pain and other complications, when given within 72 hours after appearance of the rash. About 20 % of patients older than 50 years continue to have pain six months after appearance of rash, despite antiviral treatment. A live attenuated VZV vaccine was licensed in Europe in 2006 for the prevention of zoster in individuals from the age of 60 years. Findings of a large clinical trial have shown that the zoster vaccine reduced the burden of illness caused by zoster among people 60 years of age or older by 61 % and the incidence of PHN by 67 %. Compared with controls, subjects who received the vaccine were 51 % less likely to develop zoster.

Estimating the number needed to vaccinate to prevent herpes zoster-related disease, health care resource use and mortality.

A clinical trial has shown that a live-attenuated varicella-zoster virus vaccine is effective against herpes zoster (HZ) and post-herpetic neuralgia (PHN). The aim of the study was to estimate the number needed to vaccinate (NNV) to prevent HZ-related outcomes. A cohort model of HZ associated disease, health care resource use and mortality was developed. Canadian population-based data were used to estimate age-specific incidence, hospitalization, quality-adjusted life-year (QALY) lost and mortality. NNV was calculated as the number of individuals needed to be vaccinated to prevent a specific HZ-related outcome during their lifetime. Different ages at vaccination were examined and probabilistic sensitivity analysis was performed. For 65 year olds, the NNV (HZ vaccine efficacy=63%, PHN vaccine efficacy=67%, no waning) to prevent a case of HZ, a case of PHN, a HZ death, a life-year lost and a QALY lost is estimated to be 11 (90% Crl: 10-13), 43 (90% Crl: 33-53), 23,319 (90% Crl: 15,312-33,139), 3762 (90% Crl: 1650-4629) and 165 (90% Crl: 105-197), respectively. Results were most sensitive to the duration of vaccine protection and the age at vaccination. The predicted NNV to prevent HZ and PHN are low even though vaccine efficacy is between 50-70%, which reflects the high incidence of these diseases among older adults. Results clearly show that the main benefit of HZ vaccination is prevention of morbidity caused by pain (as measured by QALYs lost) rather than mortality.

The potential cost-effectiveness of vaccination against herpes zoster and post-herpetic neuralgia

A clinical trial has shown that a live-attenuated varicella-zoster virus vaccine is effective against herpes zoster (HZ) and post-herpetic neuralgia (PHN). The aim of this study was to examine the cost-effectiveness of vaccination against HZ and PHN in Canada. A cohort model was developed to estimate the burden of HZ and the cost-effectiveness of HZ vaccination, using Canadian population-based data. Different ages at vaccination were examined and probabilistic sensitivity analysis was performed. The economic evaluation was conducted from the ministry of health perspective and 5% discounting was used for costs and benefits. In Canada (population=30 million), we estimate that each year there are 130,000 new cases of HZ, 17,000 cases of PHN and 20 deaths. Most of the pain and suffering is borne by adults over the age of 60 years and is due to PHN. Vaccinating 65-year-olds (HZ efficacy=63%, PHN efficacy=67%, no waning, cost/course=$150) is estimated to cost $33,000 per QALY-gained (90%CrI: 19,000-63,000). Assuming the cost per course of HZ vaccination is $150, probabilistic sensitivity analysis suggest that vaccinating between 65 and 75 years of age will likely yield cost-effectiveness ratios below $40,000 per Quality-Adjusted Life-Year (QALY) gained, while vaccinating adults older than 75 years will yield ratios less than $70,000 per QALY-gained. These results are most sensitive to the duration of vaccine protection and the cost of vaccination. In conclusion, results suggest that vaccinating adults between the ages of 65 and 75 years is likely to be cost-effective and thus to be a judicious use of scarce health care resources.

Evaluation of the cost-effectiveness in the United States of a vaccine to prevent herpes zoster and postherpetic neuralgia in older adults

Context A live-attenuated varicella–zoster virus vaccine, demonstrated to reduce the incidence of herpes zoster (HZ) and postherpetic neuralgia (PHN) and the morbidity associated with incident HZ and its sequelae, has recently been approved for use in the United States (U.S.). Objective To examine the potential value of zoster vaccine for society and payers. Design, setting and population An age-specific decision analytic model was designed to estimate the lifetime costs and outcomes associated with HZ, PHN and other HZ-related complications for vaccinated and non-vaccinated cohorts aged ≥60 years. Clinical trial data, published literature and other primary studies were used to inform the model. Robustness of results to key model parameters was explored through a series of one-way, multivariate and probabilistic sensitivity analyses. Both societal and payer perspectives were considered. Main outcome measure Incremental cost per quality-adjusted life year (QALY) gained. Results For a representative cohort of 1,000,000 U.S. vaccine recipients aged ≥60 years, use of the zoster vaccine was projected to eliminate 75,548–88,928 HZ cases and over 20,000 PHN cases. Over 300,000 outpatient visits, 375,000 prescriptions, 9700 ER visits and 10,000 hospitalizations were projected to be eliminated with the vaccine translating into savings of US$ 82 million to US$ 103 million in healthcare costs associated with the diagnosis and treatment of HZ, PHN and other HZ-related complications. Cost-effectiveness ratios range from US$ 16,229 to US$ 27,609 per QALY gained, depending on the input data source and analytic perspective. Results were most sensitive to PHN costs, duration of vaccine efficacy, vaccine efficacy against PHN and HZ, QALY loss associated with pain states and complication costs. Conclusions The zoster vaccine at a price of US$ 150 is likely to be cost-effective for a cohort of immunocompetent U.S. vaccine recipients aged ≥60 years using commonly cited thresholds for judging cost-effectiveness. Conclusions are robust over plausible ranges of input parameter values and a broad range of scenarios and age cohorts.

Safety of vaccinating sibling donors with live-attenuated varicella zoster vaccine before hematopoietic stem cell transplantation

Reactivation of varicella zoster virus (VZV), clinically manifested as herpes zoster (HZ) is a common complication after hematopoietic stem cell transplantation (HSCT). The optimum prophylaxis for this disease has not been defined. In this study, we examined the effects of vaccinating donors with a live-attenuated vaccine with particular reference to their immune responses and the outcome of HSCT patients. Forty prospective HLA-matched sibling donors were vaccinated before HSCT. There were humoral immune responses in both sero-positive (P<0.01) and sero-negative (P=0.058) donors. Cellular immune response was assayed in 26 donors. Significant correlation was observed between cellular immune responses as enumerated by thymidine incorporation and interferon gamma secretion (P<0.001) and the latter was used in subsequent analyses. Significant response was observed in sero-negative (6/26) and a group of sero-positive (13/26) donors while 7/26 sero-positive donors showed no response. Thirty-four HSCT were performed. These patients have a lower, albeit insignificant, risk of HZ compared with historical controls and only 3/34 patients developed single dermatomal HZ at 6, 9 and 28 months after HSCT. No patients developed VZV-related mortality. Vaccinating donors with live-attenuated VZV vaccine was safe, but whether it confers a significant protection to the patients would require further study.

Varicella vaccination in a child with acute lymphoblastic leukaemia

In July, 2003, during reinduction treatment 5 months after diagnosis of acute lymphoblastic leukaemia (ALL), a 4-yearold girl presented with generalised tonic-clonic seizures. She had been treated according to protocol ALL-BFM 2000. Cranial CT and analysis of cerebrospinal fl uid showed no signs of cerebral haemorrhage. Ultra sonography showed an enlarged liver and no signs of ascites or veno-occlusive disease. Her skin appeared normal, with no vesicular rashes. Blood tests showed only raised concentrations of aminotransferases. During the next few hours, she developed respiratory insuffi ciency, petechiae, haematomas, and vesicular lesions of the oral and vagi nal mucosal. On the assumption of an underlying infec tious cause, intravenous treatment with piperacillin, sulbactam, tobramycin, IgG, and aciclovir was initiated. 48 h after the fi rst seizure, her laboratory test results deteriorated, with aspartate and alanine aminotransferase concentrations increasing to 20 864 U/L and 16 029 U/L, respectively, and the full blood cell count indicated pancytopenia. Within 12 h, she developed multi-organ failure (liver, renal, and circulatory failure, and acute respiratory distress syndrome [ARDS]), necessitating artifi cial ventilation. Serostatus for varicella-zoster virus (VZV) was negative, but PCR for VZV was positive in peripheral blood samples (7×106 genome copies per mL). VZV was also isolated from a nasopharyngeal swab but not from cerebrospinal fl uid. PCR analysis of peripheral blood was negative for hepatitis B and C viruses, herpes simplex virus 1 and 2, Epstein-Barr virus, cytomegalovirus, adenovirus, enterovirus, human herpes virus 6, and parvovirus B19. High doses of VZVIgG were added to the treatment. Despite haemo dialysis and ventilation, the child died of progressive ARDS and multi-organ failure 10 days after admission. On receiving the positive VZV-PCR results, the mother recalled that her daughter had received live attenuated VZV vaccine (Varilrix) at another hospital 32 days before the onset of symptoms. Partial sequencing of VZV genes 38 and 54 isolated from the patient excluded a wild-type VZV infection and showed that viraemia was caused by the VZV vaccine strain OKA (fi gure). Vaccination was done 5 months after complete remission had been achieved; at that time lymphocyte count was more than 1·5×109/L, and chemotherapy was interrupted for 1 week before and after vaccination. Deaths after vaccinations with numerous attenuated viruses are well established. Fatal wild-type VZV infections have been reported in ALL patients during chemotherapy and after bone-marrow cell transplantation. Therefore, VZV vaccination is a useful, and generally accepted, therapeutic measure for patients with ALL in remission. Studies of VZV vaccination 3–4 months after autologous stem-cell transplantation, and in early ALL maintenance therapy, did not show fatal side-eff ects. However, any interruption of maintenance therapy in ALL can adversely aff ect outcome for the patient. In our patient, liver failure developed 5 weeks after VZV vaccination, which indicates longstanding replication of OKA strain in the liver. This suggestion accords with observations of late onset of complications (fever, vesicles, and severe hepatitis) in immunocompromised patients after VZV vaccination. Therefore, although we cannot fully exclude that intensifi cation of chemotherapy could have aggravated her symptoms, we suggest that VZV vaccination in seronegative children with leukaemia, who are in complete remission for at least 12 months, should not be undertaken until at least 9 months after the end of immunosuppressive treatment (including maintenance therapy) and not before a lymphocyte count of at least 1·5×109/L has been ascertained. In addition, high-risk patients should remain under close surveillance in the critical phase (6 weeks after vaccination) so that immediate antiviral treatment with aciclovir can be initiated in symptomatic children.

Variability and gender differences in memory T cell immunity to varicella-zoster virus in healthy adults

Latent varicella zoster virus (VZV) can reactivate and cause zoster, the prevention of which relies upon cellular immunity to VZV. To assess temporal variation of VZV cell-mediated immunity in healthy naturally immune adults, we evaluated VZV-specific responder cell frequencies (RCF) longitudinally over 1 year in each of 25 adults. VZV-specific CD4+ T cells were detected ( p < 0.003) and showed minimal variability in RCF. Additional analysis of VZV T cell RCF revealed differences between genders, with only males ( p < 0.005) having detectable VZV-specific memory CD4+ T cell responses by this method. Taken together, results suggest that further studies regarding immunization of younger adults and females with the modified, high-potency live attenuated VZV vaccine may be warranted.

Immunogenicity of a two-dose regime of varicella vaccine in children with cancers.

Live-attenuated varicella vaccine is effective and safe in immunocompetent children. In this study, we assess the immunogenicity and adverse events following varicella vaccination in immunosuppressed cancer children. Varicella-zoster virus (VZV)-seronegative cancer children received two doses of live-attenuated VZV vaccine (Varilrix) in a span of 3 months. Patients with acute lymphoblastic leukaemia (ALL) were in the maintenance phase of chemotherapy, whereas those with solid tumours joined the study around 3-6 months from treatment discontinuation. VZV-specific cellular and humoral immune responses were measured before and after VZV vaccination. The median (range) age of the 17 patients was 4.4 yr (2.0-14.5). Thirteen had ALL, one had myelodysplastic syndrome and three had solid tumours. Following vaccination, the VZV-specific stimulation index (SI) increased from 1.7 (0.9-2.9) to 17.9 (5.9-36.0) (P < 0.001). Similarly, SI to phytohaemagglutinin mitogen increased from 1136 (499-1930) to 1714 (848-2518) (P = 0.028). There were also significant increases in CD4+ cells and CD4:CD8 ratio as well as a reduction in CD16/56+ cells in peripheral blood lymphocytes. Seroconversion rate to VZV was 19% after one dose and increased to 94% after the second dose of VZV vaccine. Serum VZV-specific IgG concentrations also increased significantly following two doses when compared with one dose of VZV vaccine (P = 0.0004). One subject developed possibly vaccine-related chickenpox with self-limiting hepatitis at 5 wk following vaccination. None of the patients developed herpes-zoster at a median (range) follow-up of 27.5 months (24.0-30.0). Non-immune cancer children can be effectively vaccinated against chickenpox at the defined period. However, the safety of chickenpox vaccine in these immunosuppressed children needs to be further studied.

Decline in varicella-zoster virus (VZV)-specific cell-mediated immunity with increasing age and boosting with a high-dose VZV vaccine.

The safety and immunogenecity of a booster dose of live attenuated varicella-zoster virus (VZV) vaccine was evaluated in 196 healthy subjects, >or=60 years old, who had already received a VZV vaccine >5 years before. This repeat booster dose was well tolerated. Cell-mediated immunity (CMI) to VZV was measured by an interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spot-forming cell (ELISPOT) assay and a limiting dilution responder cell frequency (RCF) assay. Prevaccination responses decreased as a function of increasing age but were detectable in all subjects by use of the IFN-gamma ELISPOT assay. In most subjects, VZV-specific CMI was increased at 6 weeks postvaccination. The magnitude of the vaccine-induced IFN-gamma ELISPOT response was inversely related to prevaccination values. Although there was a significant correlation between the IFN-gamma ELISPOT and RCF assays, the ELISPOT assay had greater sensitivity and a wider dynamic range. A live attenuated VZV vaccine is safe and immunogenic in an elderly population, and the vaccine-induced immunity may be monitored by the IFN-gamma ELISPOT assay.

Persistence of immunity to varicella-zoster virus after vaccination of healthcare workers.

Varicella-zoster virus (VZV) vaccine is recommended to protect susceptible healthcare workers (HCWs) from serious disease and to prevent nosocomial spread of VZV. We evaluated clinical outcomes and serological responses in HCWs after immunization with live attenuated VZV vaccine. Vaccinees were immunized from 1979 to 1998 during VZV vaccine trials, as well as after licensure, and followed prospectively for 1 month to 20.6 (mean 4.6) years after vaccination. Sera were tested by fluorescent antibody to membrane antigen (FAMA), latex agglutination (LA), and enzyme-linked immunoassay (EIA) to detect VZV-specific antibodies. The median age of the 120 HCWs was 26 years; 51 (42%) were males. Ninety eight (82%) of these study subjects received vaccine prepared by Merck and 22 (18%) by SmithKline Beecham; 25, 81, and 14 vaccinees received one dose, two doses, and three doses, respectively. The crude attack rate was 10%; 12 of 120 HCWs developed chickenpox 6 months to 8.4 years after vaccination. The attack rates following household and hospital exposures were 18% (4/22) and 8% (6/72), respectively. All resulting illness was mild to moderate (mean 40 vesicles). Seroconversion after vaccination was documented by FAMA in 96% of HCWs, although 31% lost detectable antibodies. Compared with FAMA, LA and EIA were 82% and 74% sensitive and 94% and 89% specific, respectively. The VZV vaccine effectively protected HCWs from varicella, particularly from serious disease. Currently available serological tests are not optimal, and improved assays are needed.

Vaccination of immunocompetent elderly subjects with a live attenuated Oka strain of varicella zoster virus: a randomized, controlled, dose-response trial

After primary infection in childhood, varicella zoster virus (VZV) remains latent in the dorsal route ganglia. Its reactivation later in life can lead to a zoster episode. VZV-specific, T-cell-mediated immunity (VZV-CMI) is likely to be important in preventing symptomatic reactivation. As CMI declines with age, a vaccine enhancing VZV-CMI might be effective in decreasing the incidence or severity of zoster in elderly subjects. A randomized, double blind controlled trial assessing CMI responses of elderly subjects immunized with a live attenuated, VZV-Oka vaccine was conducted. Two hundred healthy volunteers (55–75 years of age) received either a single injection of the VZV vaccine (PMC), containing 3200 (Oka 3200), 8500 (Oka 8500), or 41,650 (Oka 41650) PFU of live VZV, or a pneumococcus vaccine control group (Pneumo 23(®). The immune response to VZV was assessed by measuring the T-cell response to VZV antigens, i.e. proliferation (stimulation index, SI), precursor cell frequency (PCF), cytokine secretion, and antibody titers. Six weeks post-vaccination, VZV-specific SI (adjusted mean values) was significantly greater ( P<0.0001) in the 3 vaccine groups (with SI=5.6 for Oka 3200; SI=5.0 for Oka 8500, and SI=7.2 for Oka 41,650) than in the control group (SI=2.9). The increase in PCF was striking, with 72.4, 91.2 and 85.1 precursors per million cells respectively in these 3 vaccine groups, vs 26.3 in the control group. No significant IL-4 secretion was observed in any subject, whereas the presence of IFN- γ secretion was found to correlate with good responder status. The increase of these CMI parameters did not depend upon the titer of virus injected. Geometric mean titers of VZV antibodies increased in all vaccine groups and remained unchanged in the control group. Nevertheless, no correlation between the antibody response and the cell-mediated response was found. Live attenuated VZV vaccine caused a significant increase in VZV-CMI in a healthy, elderly population. No relationship between vaccine dose and the intensity of the specific response was found.

Analysis of the Persistence of Humoral and Cellular Immunity inChildren and Adults Immunized With Varicella Vaccine

1. Zerboni L, 2. Nader S, 3. Aoki K, 4. Arvin AM (1998) J Infect Dis. 177:1701–1704. [OpenUrl][1][Abstract/FREE Full Text][2] #### Purpose of the Study To evaluate the persistence of humoral and cellular immunity to varicella-zoster virus (VZV) in children and adults immunized with live attenuated VZV vaccine. ##### Study Population Two hundred healthy children (ages 2–12 years) and forty healthy adults (ages 13–45 years) were vaccinated and identified as seroconverters who did not develop breakthrough varicella. Of these individuals, 60 children and 18 adults agreed to be reevaluated. … [1]: {openurl}?query=rft.jtitle%253DJ%2BInfect%2BDis.%26rft_id%253Dinfo%253Adoi%252F10.1086%252F517426%26rft_id%253Dinfo%253Apmid%252F9607852%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=ABST&journalCode=jinfdis&resid=177/6/1701&atom=%2Fpediatrics%2F104%2FSupplement_2%2F402.2.atom

Use of a live attenuated varicella vaccine to boost varicella-specific immune responses in seropositive people 55 years of age and older: duration of booster effect.

Varicella-zoster virus (VZV)-specific T cell immunity was measured in 130 persons > or = 55 years of age 6 years after they received a live attenuated VZV vaccine. Circulating T cells, which proliferated in vitro in response to VZV antigen, were enumerated (VZV responder cell frequency assay). Six years after the booster vaccination, the VZV-responding cell frequency (1/61,000 circulating cells) was still significantly (P < .05) improved over the baseline measurements (1/70,000) and appears to have diminished the expected decline in frequency as these vaccinees aged (to 1/86,000). Ten herpes-zoster--like clinical events were recorded. Although the frequency of these events, approximately 1/100 patient-years, is within the expected range of such events for this age cohort, the number of lesions was small, there was very little pain, and there was no postherpetic neuralgia. These results support the development of a vaccine to prevent or attenuate herpes zoster.

Analysis of the persistence of humoral and cellular immunity in children and adults immunized with varicella vaccine.

The persistence of humoral and cellular immunity to varicella-zoster virus (VZV) was evaluated in 60 children and 18 adults immunized with live attenuated VZV vaccine. At a mean of 5 years after vaccination, 93% of children and 94% of adults had IgG antibodies to VZV as determined by ELISA. VZV antibody concentrations were significantly higher at 5 years than at 1 year after immunization in children and adults. Cell-mediated immunity to VZV was detected in 87% of children and 94% of adults at 5 years. The mean stimulation index was significantly higher at 5 years than at 1 year among children and adults. Cytokine responses to VZV, including interleukin-2, interferon-gamma, and interleukin-10 were equivalent between children and adults at 5 years. In summary, varicella immunization induced long-term humoral and cellular immunity, and initial differences between cell-mediated responses in children and adults diminished over time.

Varicella vaccination in children after bone marrow transplantation.

Herpes zoster (HZ) is one of the most common complications after bone marrow transplantation (BMT) in children. Apart from treatment with antiviral drugs, effective prevention by active immunization with varicella-zoster virus (VZV) appears to be possible. In this study 15 patients were vaccinated with a live attenuated VZV vaccine (Varilrix) 12-23 months after BMT. The vaccine was well tolerated without adverse reactions. Chickenpox or HZ were not observed for up to 2 years after immunization. Eight out of nine seronegative patients seroconverted and in six virus-specific IgG could still be demonstrated 2 years later. The incidence of VZV diseases in 133 non-immunized children after BMT was 26.3%. Infections usually occurred within 18 months after BMT.

Viral skin infections

The new antiviral drugs famiciclovir and valacyclovir are effective for the treatment of recurrent gential herpes and herpes zostar and may be given less frequently than acyclovir. Asymptomatic shedding of herpes simplex virus type 2 may be reduced by administration of daily acyclovir. Recombinant genetic techniques that allow viral protein production in vitro are being used in herpes simplex and papilloma virus vaccine development. Administatrtion of a live attenuated varicella-zoster virus vaccine provides long-lasting measures of cellular immunity in the elderly.