Zoster - Shingles

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Shingles, also known at herpes zoster, is a painful rash caused by the same virus that causes chickenpox.The rash begins as a cluster of small red spots that often blister and can be exquisitely painful. The chickenpox virus (VZV) sometimes remains dormant in the sensory nerve ganglia after a chickenpox infection.

The virus can be reactivated when: 1) long term immune status wanes without subsequent exposure from children who have chickenpox vaccines.; 2) with aging; 3) with immunocompromising conditions such as diabetes; or 4) with treatments such as steroids or biologics. Shingles rashes generally last 30 days but the persistent pain can last many months, In some people, if the pain becomes permanent, it is called post-herpetic neuralgia. The residual scarring as the rash heals can be extensive. We have now created vaccines to prevent a problem caused by a vaccine (chickenpox). The risk of developing post-herpetic neuralgia also increases with age. Two shingles vaccines have been developed, Zostavax (Merck) and Shingrix (GSK), for individuals over 50 years-old for the prevention of shingles.

Dr. Tenpenny's article on Zostavax here. 

Product Information

'R'elated Information

VAERS Adverse events Results for Zostavax 

Trust Me: I Have The Statistics To Prove Itby Dr. F. Edward Yazbak“Merck then helped fund research to test Zostavax (zoster live vaccine from  Oka/Merck), a higher potency vaccine intended to prevent shingles, a disease that increased by 90 percent over four years after the introduction of Varivax, according to the CDC. After a three-year trial, it appears that Zostavax can reduce the incidence of shingles by 50 percent.”

February 2020Vaccine-Strain Herpes Zoster Ophthalmicus in a 14-month-old Boy Prompting an Immunodeficiency Workup - Case Report and Review of Vaccine-strain Herpes Zoster "HSV PCR was negative. VZV PCR was positive, and the Wisconsin State Laboratory of Hygiene confirmed a positive test for the vaccine-strain. ... Given the potentially serious consequences of HZ and the possible association between HZ and immunodeficiency, pediatricians must be equipped to recognize and manage this disease. Herein, we provide an overview of pediatric HZ and review the underlying immunology. ... Moodley et al11 describe a case of vaccine-strain HZ on the left lower back of an immunocompetent 3-year old who received the varicella vaccine in his right upper arm 19 months prior. The HZ location may reflect a period of viremia in which latency was established in neurons distant from the site of vaccination. Genetic sequencing of the vaccine-strain virus showed a wild-type allele rather than a vaccine-type allele within ORF0, an open reading frame with a potential role in vaccine attenuation."

January 29, 2020 Safety of inadvertent administration of live zoster vaccine to immunosuppressed individuals in a UK-based observational cohort analysis (pdf) "Despite evidence of inadvertent vaccination of immunosuppressed individuals with live zoster vaccination, there is a lack of evidence of severe consequences including hospitalisation. This should reassure primary care staff and encourage vaccination of mildly immunosuppressed individuals who do not meet current thresholds for contraindication. These findings support a review of the extent to which live zoster vaccination is contraindicated among the immunosuppressed."

October 23, 2019 2778. Impact of Reactogenicity on Quality of Life and Physical Functioning in Adults ≥50 Years Receiving Both Doses of the Adjuvanted Recombinant Zoster Vaccine "In days 1–2, post-second RZV dose, a transient, clinically-important decrease in SF-36 PF score (table) was seen in those reporting grade 3 solicited symptoms, which impacted activities such as walking and climbing stairs."

January 2, 2018 – Immunogenicity and safety of zoster vaccine live administered with quadrivalent influenza virus vaccine (full text) “ZV (zoster vaccine) administered concomitantly with IIV4 (quadravalent influena vaccine) was generally well tolerated. Overall, the vaccination groups were comparable with regard to proportions of subjects reporting AEs through 28 days following any vaccination...Of note, injection-site erythema and swelling were reported by size; after ZV, ∼90% of erythema and swelling were ≤3 in. in both groups, and ∼82% after influenza vaccineVaccine-related injection-site and systemic AEs were slightly more common in subjects 50–59 years old than in the two older age groups.”

December 19, 2017 – Herpes zoster vaccine live: A 10-year review of post-marketing safety experience“Over the 10 years of post-marketing use, a total of 45,898 adverse events (AEs) were reported. 93% were non-serious. 4,607 (8.5%) were serious (Table 2). Comment: More than 3800 persons contracted shingles from the vaccine with two deaths and 36% did not recover, meaning, they most likely went on to develop post-herpetic neuralgia. Disseminated herpes zoster can be deadly; ADEM can be deadly; herpes zoster opthalmicus can cause blindness. There were 74 deaths that were dismissed as "not associated" - but who knows for sure? Consider these ramifications with a vaccine that at best prevents shingles 50% of the time.

In a summary of post-marketing reports:

  • Injection-site reaction (ISR) - 4,355 reports- erythema, swelling, pain warmth, pruritis. Median time to onset was 2 days. Of the 74% of reports with outcome reported, 61% recovered. 
  • Herpes zoster (HZ) - 3,810 reportshas developed shingles after immunization (3943 AEs; 373 were serious). Time to onset varied from two weeks (53%) to six weeks (65%). Of the those with an outcome reported, 64% recovered. There two reports of death with shingles (HZ) listed as the cause of death.
  • Varicella and Varicella-like rash - There were 221 reportsof varicella rash after the immunization. 29 were listed as serious.
  • Rash - There were 1922 reports of one or more rash terms that were non-shingles and non-chickenpox rash. Of these, 185 were listed as serious. Of those reported, 66% recovered.
  • Hypersensitivity-anaphylaxis - there were 190 reports of adverse events and 80 serious adverse events reported with the median onset 3 days post vaccination. 
  • Disseminated herpes zoster - there were 19 AEs and 14 Serious AEs suggesting of disseminated herpes zoster with four reports of visceral (internal organ) involvement. Vaccine-strain virus (VSV Oka/Merck) was confirmed by PCR analysis. Of the 14 reports without visceral involvement, 4 had immunocompromised conditions and/or concomitant use of immunosuppressive therapies.
  • Ophthalmic HZ  - HZO - (shingles around the eye) - 141 reports, 32 were serious,with the median age of 71 years. Median time to onset was 56 days post vaccination. 63% recovered.
  • CNS experiences - 498 reports, with 100 serious, involved central nervous system side effects. The most common was headache, followed by encephalitis and ataxia.Acute disseminated encephalomyelitis (ADEM) was reported in three persons. The median time to onset of CNS events was two days post vaccination.
  • Herpes zoster Oticus (Ramsy Hunt syndrome)- 14 events of HZ Oticus, palsy of the VIIth cranial nerve. Median time to onset was 18 days. Of those reporting an outcome, 4 of 9 recovered. 
  • Fatal outcome reports - There were 74 deathsthat were deemed to be temporal, but not causally associated with shingles vaccination. Study investigators related to the reports were related to pre-existing conditions (cardiac) or immune compromise.

In conclusion, the results of this review found that the safety profile of Zostavax, following 10 years of post-marketing use and >34 million doses distributed, remains favorable and consistent with that observed in clinical trials and post-licensure studies

  • This research was funded by Merck & Co., Inc., Kenilworth, NJ, USA (sponsor). In conjunction with the external investigators, this research was designed, executed, and analyzed by the sponsor. Although the sponsor formally reviewed a penultimate draft of this manuscript, the opinions expressed are those of the authorship and may not necessarily reflect those of the sponsor. All co-authors approved the final version of the manuscript.
  • Potential conflicts of interest EW, MW, EB, ZP, PS, PA are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA and may own stock or stock options in the company.

'December 15, 2017 – The effectiveness of shingles vaccine among Albertans aged 50 years or older: A retrospective cohort study (full text) This study suggests the effectiveness of the shingles vaccine in preventing an incident episode of shingles was highest during the first year following vaccinatio'n at 50.02%, and quickly loses any protective effect by the fifth year following vaccination. Our findings provide data to inform policy-makers when making decisions related to public funding of the shingles vaccine. Comment: At it's best, it prevents shingles 50% of the time (or was that the luck of a coin toss?) And then, will all the possible side effect, antibodies are gone in five years. Worth the risk?

December 4, 2017 – A randomized lot-to-lot immunogenicity consistency study of the candidate zoster vaccine HZ/su “Of 651 participants enrolled in the study, 638 received both doses of the HZ/su vaccine and 634 completed the study. Humoral immune responses were robust and consistency between 3 manufacturing lots was demonstrated. The incidence of solicited symptoms, unsolicited AEs and SAEs was comparable between all lots. Three fatal SAEs, 1 in each lot, were reported, none of which were considered vaccine-related by investigator assessment. Two out of the 8 reported pIMDs were considered vaccine-related by the investigator.” Comment: There it is again...with a stroke of a pen, the three deaths were negated, because they said so.

December 2017 – Clinical Usage of the Adjuvanted Herpes Zoster Subunit Vaccine (HZ/su): Revaccination of Recipients of Live Attenuated Zoster Vaccine and Coadministration With a Seasonal Influenza Vaccine (full text) “The most frequent debilitating complication of HZ is postherpetic neuralgia (PHN) reflecting damage to the sensory ganglion in which the latent virus reactivated and to adjacent neural structures. Early treatment with antiviral drugs reduces the severity and duration of HZ but does not prevent the development of PHN, which may persist for months or years and is frequently refractory to treatment....More than a million new cases of HZ occur each year in the United States, and this number is increasing with aging of the population and the increased use of immunosuppressive therapies.

  • The Shingles Prevention Study (SPS) demonstrated that the zoster vaccine (ZVL):
    • Reduced burden of HZ illness by 61.1% (65.5% in subjects aged 60–69 yrs; 55.4% in subjects aged ≥70 yrs). The burden of illness is a measure the incidence, severity, and duration with its associated pain and discomfort.
    • Reduced the incidence PHN by 66.5% (65.7% in subjects aged 60–69 yrs; 66.8% in subjects aged ≥70 yrs), and
    • Reduced the incidence of shingles by 51.3% (63.9% in subjects aged 60–69 years, but only 37.6% in subjects aged ≥70 years).
    • Reduced the incidence of HZ  by 69.8%  (in subjects aged 50–59 years).
  • Potential conflicts of interest.  D. M. K. has served as a consultant to GlaxoSmithKline and Biomedical Research Models; has received research funding from Merck, Admedus Immunotherapy, Sanofi Pasteur, Vical, and Immune Design Corporationand is a co-inventor on patents owned by the University of Washington concerning viral vaccines.

December 2017 – Immunogenicity and Safety of the HZ/su Adjuvanted Herpes Zoster Subunit Vaccine in Adults Previously Vaccinated With a Live Attenuated Herpes Zoster Vaccine (full text) “In sum, we show that after vaccination with HZ/su, the antibody response in adults who were previously vaccinated with the live attenuated zoster vaccine was non-inferior (i.e. had the same antibody response) to that in adults without any previous vaccination against HZ. Robust cellular immune responses were observed in both groups. No clinically significant differences in safety and reactogenicity were observed between the 2 study groups. Taken together, HZ/su may be an attractive option to revaccinate prior ZVL recipients.” Comment: Perhaps the outcome of this study and the analysis has something to do with the investigators potential conflicts of interest (below).

  • Financial support. This work was supported by GSK Biologicals SA, which was involved in all stages of the study conduct and analysis, and also took responsibility for all costs associated with the development and publishing of the present manuscript.
  • Potential conflicts of interest. L. C., M. D., K. G., I. V., and L. O. are employed by the GSK group of companies.
  •  I. V. and L. O. own stock optionsas part of their employee remuneration.
  • T. C. H. and H. L. were employed by the GSK group of companies at the time this study was designed and received stock as part of employee remuneration.
  • H. L. is currently employed by Pfizer Inc. T. C. H. is co-inventor of the patent application related to the vaccine used in this study and is currently a consultant for the GSK group of companies.
  • N. K. reports 'receiving grants from the GSK group of companies during the conduct of this study, as well as receiving grants from Merck & Co, Pfizer Inc, Sanofi Pasteur, MedImmune, Novartis, and Protein Scienc'e for work outside of this study.
  • J. P. reports receiving principal investigator fees from the GSK group of companies during the conduct of the study. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

September 26, 2017 – Clinical Usage of the Candidate Adjuvanted HZ/su Zoster Vaccine: re-vaccination of recipients of live attenuated zoster vaccine and co-administration with a seasonal influenza vaccine (pdf) “The proliferation of new vaccines and vaccine combinations makes it impossible to base all judgments regarding vaccine usage on results from large, controlled clinical trials. Instead, these decisions will have to be based on the results of smaller clinical trials with laboratory measures of clinically relevant correlates of protection as endpoints. For the many vaccines under development that target diseases caused by persistent viral infections, such as herpes zoster, for which elements of CMI are the host defenses of primary importance, it will be important to utilize common protocols and validated laboratory measures of CMI to facilitate comparisons. Intracellular cytokine staining and flow cytometry is a candidate technology for measurements of virus-specific CMI that can be validated and used to compare studies of candidate vaccines. Agencies like the US FDA that license vaccines should take the lead in encouraging the development of such studies.” Comment: In other words, prevention of shingles is NOT just about developing an antibody response to the vaccine.

July 2017 – Keratitis in association with herpes zoster and varicella vaccines.The mechanism may be the persistence of viral antigens in the cornea after VZV vaccination or herpes zoster ophthalmicus. This reaction is probable, given the plausible biological mechanism, the temporal relationship between vaccination and keratitis, and overall patterns of presentation after vaccination.” Comment: Herpes zoster ''ophthalmicus'', or shingles around the eye, can lead to blindness in that eye.

June 14, 2017 – When zoster hits close to home: Impact of personal zoster awareness on zoster vaccine uptake in the U.S. “U.S. zoster vaccine uptake has been sluggish. Most adults are aware of zoster but unaware of its distressing manifestations. We found that vaccine uptake is markedly increased immediately following the occurrence of zoster in a spouseComment: The corollary to this is that vaccine uptake dramatically STOPS when an immediate family member has a serious side effect or dies after a vaccination. 

May 31, 2017 – Serum C-reactive protein and congestive heart failure are significant predictors of the herpes-zoster vaccine response in the nursing home elderly  “We examined 187 elderly nursing home residents (aged 80–102 years) and 50 community-dwelling seniors (aged 60–75 years) vaccinated with the live-attenuated varicella-zoster virus (VZV) vaccine. Specifically, we examined whether vaccine responsiveness was associated with serum C-reactive protein (CRP), tumor necrosis factor, interleukin 1β, 6, and 10, leukocyte telomere length, chronic disease status, and frailty. Results: Elderly participants had significantly higher levels of CRP, tumor necrosis factor, and interleukin 6 and shorter leukocyte telomere length. Vaccine responsiveness was inversely related to the CRP level in elderly participants,..... those with congestive heart failure (CHF) were less likely to achieve a 2-fold response (odds ratio, 0.08). Conclusions: In summary, this data suggests that certain risk factors are associated with a greater likelihood of vaccine failure.” Comment: Previous studies have shown that the incidence of shingles is only reduced by 69.3% in subjects aged 60–69 years, and 37.6% in subjects aged ≥70 years. Now we see that those with chronic inflammation and CHF do not respond.

April 25, 2017 – Sociodemographic predictors of variation in coverage of the national shingles vaccination programme in England, 2014/15 “Patients’ ethnicity and IMD are predictors of coverage which contribute to, but do not wholly account for, geographical variation coverage. Interventions to address service-related, sociodemographic and ethnic inequalities in shingles vaccine coverage are required.”

December 20, 2016 – The Relationship Between Herpes Zoster, Syphilis and Chickenpox “Originally regarded as occurring along the distribution of peripheral nerves, it has been recognized, since the epoch-marking discoveries of Henry Head, as having a segmental distribution. Certain aspects of the disease, particularly its relationship to syphilis, have recently been discussed by Brown and Dujardin. These observers noted that herpes zoster was distinctly more prevalent among a group of soldiers under observation for syphilis than it was among an unselected group of patients from the civilian population of the district. Among the syphilitics, zoster occurred in a proportion of four cases per thousand, while among the general population zoster only occurred in  one case per thousand.”

December 13, 2016 – Anaphylaxis after Zoster Vaccine: Implicating Alpha-Gal Allergy as a Possible Mechanism “A patient with alpha-gal allergy presented with anaphylaxis after receiving zoster vaccine. Subsequent testing of selected vaccines revealed the presence of alpha-gal allergen in MMR and zoster vaccines, which have in common a higher content of gelatin and content of bovine calf serum.COMMENT: Alpha-gal is short for galactose-alpha-1,3-galactose, a carbohydrate found in the cells of many mammals that humans eat, such as cows, sheep, and pigs. As the article suggests, VAERS had 202 reports of severe allergic reactions after the herpes zoster vaccine, with 14 reports of anaphylaxis.  Five of 14 (36%) of these patients had a known associated beef, pork, gelatin, or alpha-gal allergy. Do physicians ask about beef, pork or gelatins allergies before administering this vaccine? Should patients be tested before receiving this vaccine? 

October 26, 2016 – Herpes Zoster Vaccine Coverage in Older Adults in the U.S., 2007–2013 (full text) “By 2013, only 1.7% of adults aged 50–59 years received the HZ vaccine. Even though the U.S. FDA approved the indication of the HZ vaccine in adults aged 50–59 years in 2011, ACIP did not give the universal recommendation to adults aged 50–59 years. For this reason, adults aged 50–59 years may not be aware of the HZ vaccine, healthcare providers may be reluctant to give the vaccine, and the insurance may not cover the vaccination.Further studies are needed to find the actual reasons for low HZ vaccination rate for adults aged 50–59 years.”

October 5, 2016 – Immunogenicity of Varicella Zoster Vaccine and Immunologic Predictors of Response in a Cohort of Elderly Nursing Home Residents “A cohort of 190 frail nursing home residents between the ages of 80 and 102 'years and a cohort of 50 community-dwelling seniors, ages 60 to 75 years, a comparison group, were vaccinated with the shingles vaccine. IFN-γ ELISpot assay was measured prior to and six-weeks following vaccination. Cellular markers of immunosenescence were measured in the nursing home elderly.  Conclusions. The Oka/Merck VZV vaccine induces VZV-immunity in elderly nursing home residents similar to the immunity produced in community-dwelling seniors.”  Comment: Later studies disproved this conclusion.

October 2016 – Deep Sequencing of Distinct Preparations of the Live Attenuated Varicella-Zoster Virus Vaccine Reveals a Conserved Core of Attenuating Single-Nucleotide Polymorphisms (full text) “However, more than 82% of the 292 variantsspecific to Merck vaccines were present in two or more batches. This, together with the finding thatat least 158 of the 292 variant alleles have previously been observed in vaccine rash cases after inoculation with VariVax vaccines, suggests that most of these mutations were acquired during the production of the working seed lotthat currently forms the basis of all batch production and not during vaccine batch production itself. COMMENT: Does this imply that every batch of shingles vaccine is different. 

September 21, 2016 – Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older  “Solicited reports of injection-site and systemic reactions within 7 days after injection were more frequent among HZ/su recipients than among placebo recipients ('79.0% vs. 29.5%). Serious adverse events, potential immune-mediated diseases, and d'eaths occurred with similar frequencies in the two study groups.”

March 23, 2016 – The Epidemiology of Herpes Zoster After Varicella Immunization Under Different Biological Hypotheses: Perspectives From Mathematical Modeling “All models predict a qualitatively similar, but quantitatively heterogeneous, transient increase of HZ incidence. In particular, novel estimates from the progressive immunity model predict the largest increase in natural HZ and the largest incidence of HZ cases from 'reactivation of the vaccine strain, which in the long term will likely outnumber prevaccination numbers. Our results reinforce the idea that a better understanding of HZ pathogenesis is required 'before further mass varicella (chickenpox) immunization programs are set out.”

May 10, 2016 – Herpes zoster and the search for an effective vaccine “Zostavax® is a vaccine approved by the Federal Drug Administration for the prevention of Herpes Zoster. Unfortunately, this vaccine 'only reduces the incidence of disease by 51% and it only reduces the incidence of postherpetic neuralgia by 66.5% when administered to those 60 and older. Moreover, it is contradicted for individuals who are immunocompromised, or receiving immunosuppressant treatments although they are at higher risk for Herpes Zoster compared to immune competent older individuals.”

February 9, 2016 – Declining effectiveness of herpes zoster vaccine in adults 60 years and older “The effectiveness of HZ vaccine decreased from 68.7%  in the first year to 4.2% in the eighth year. This rapid decline suggests that arevaccination strategy may be needed, if feasible.”

February 3, 2016 – Long-term immunogenicity and safety of an investigational herpes zoster subunit vaccine in older adults (full text) “Over the whole study period, reported SAEs were consistent with expectations for this population of adults aged 60 years or older at the time of vaccination, such as cardiovascular disorders and cancers. No SAEs were considered related to vaccination. Also, no safety concerns related to immune-mediated diseases were identified between month 36 and month 72.”

  • Funding This work was supported by GlaxoSmithKline Biologicals SA, Belgium, which paid for all costs associated with the development and the publishing of the present manuscript. The sponsor was involved in all stages of the study conduct and analysis. Trademarks Zostavax is a registered trademark of Merck & Co., Inc.
  • Conflict of interest statement All study sites received a grant from GlaxoSmithKline Biologicals SA for carrying out this clinical trial. R.C. and T.S. report receiving grants from GSK outside the submitted work. G.C., H.L., and T.C.H. are GSK employees. 

October 9, 2015 – Administration of a Second Dose of Herpes Zoster Vaccine Ten Years After a First Dose “These findings support further investigation of the ZV administration in early versus later age, and of booster doses for elderly individuals at an appropriate interval after initial immunization against HZ.”

September 17, 2015 – Zoster Vaccine at Age 50? The duration of zoster vaccine effectiveness appears to be short enough that earlier is not better when it comes to protecting older adults. This analysis joins others in affirming age 60 as the sensible time to begin vaccinating healthy immunocompetent adults.”

June 13, 2012 – Unsettled Issues of Zostavax Vaccine “Unfortunately, the influence of Zostavax on other serious complications of latent VZV such as meningitis, encephalitis, myelitis, angiopathy, and ophthalmologic infections has not been adequately evaluated. Headache was the most frequent serious adverse event but no information is provided regarding etiology. “…”No Hispanics were included, and white women, all from developed nations, were over-represented. Long-term follow-up of Zostavax recipients is prudent and necessary.”

April 23, 2012 – Safety of zoster vaccine in adults from a large managed-care cohort: a Vaccine Safety Datalink study “The risk of allergic reaction was significantly increased within 1–7 days of vaccination [relative risk = 2.13, 95% confidence interval (CI): 1.87–2.40 by case-centred method and relative rate = 2.32, 95% CI: 1.85–2.91 by SCCS].”

September 19, 2011 – Family history and herpes zoster risk in the era of shingles vaccination “The results indicate a stronger association between herpes zoster and family history of herpes zoster than previously reported in the literature and suggest a genetic predisposition to herpes zoster may be more frequently inherited along maternal lines.”

July 15, 2012 – Zoster Vaccine: Current Status and Future Prospects “Differences in strain content are observed among Oka vaccines produced by different manufacturers, and even among different batches from the same manufacturer(Table 1). This underlines the importance of genotyping VZV strains from vaccine-associated illnesses, including herpes zoster.”

August 2010 – Exacerbation of Zoster Interstitial Keratitis After Zoster Vaccination in an Adult (full text) “We report a case of severe worsening Interstitial Keratitis (IK) 35 days after vaccination with Zostavax. This exacerbation of the patient’s IK was much worse than prior episodes. Given the immune pathogenesis of IK and the temporal association of this episode of IK with recent shingles vaccination, it is likely that the more severe recurrence of the keratitis was a consequence of the increased immune response elicited by the herpes zoster virus in the vaccine. The interval between vaccination and reactivation of the immunogenic stromal keratitis is consistent with the time needed for antigen processing and immune response.” Comment: Interstitial keratitis is chronic, nonulcerative inflammation middle layers of the cornea. The cause is usually infectious and can often lead to blindness. 

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May 2010 – Recommendations of the Advisory Committee on Immunization Practices (ACIP) “Among vaccine recipients, the attenuated Oka/Merck strain of varicella-zoster virus, which is included in varicella vaccine AND the shingles vaccine, can establish a latent infection and clinically reactivate as zoster (97). Zoster caused by Oka/Merck strain varicella-zoster vaccine-strain virus cannot be distinguished on clinical grounds from zoster caused by wild-type varicella-zoster virus. The risk for zoster caused specifically by Oka/Merck strain VZV is unknown because recipients of varicella (chickenpox) vaccine might have already been infected with wild-type virus or might have become infected with wild-type virus following vaccination (i.e., due to vaccine failure) that could also reactivate.” Comment: This link, to the ACIP document, is worth reading to more fully understand this vaccine and the viruses.

October 1, 2009 – Varicella-Zoster Virus–Specific Immune Responses to Herpes Zoster in Elderly Participants in a Trial of a Clinically Effective Zoster Vaccine (full text)  This was a randomized, double-blind, placebo-controlled trial in 38,546 subjects ⩾60 years of age done in conjunction with the US Department of Veterans Affairs. "In this study, we evaluated the association between immune responses to HZ and both HZ disease severity and the occurrence of PHN, as well as the effect of zoster vaccine and of key demographics on immune responses to HZ"......."Overall, 981 subjects had confirmed shingles (after the shot), 283 had rashes with other causes, and 1395 were further enrolled in the SPS Immunology Substudy with longitudinal VZV immune response data. Varicella-zoster vaccine antibody (shingles vaccine) responses did not correlate with protection against the severity of HZ or PHN. At 3 weeks after HZ onset, gpELISA titers were greater in subjects with more severe disease. Higher antibody titers were associated with increased HZ severity and occurrence of postherpetic neuralgia. COMMENT: This is an important study. It confirms that TH1/CMI arm of the immune system is key to preventing shingles. The higher the antibody titer AFTER a vaccine, the greater the risk of developing shingles '''''from the vaccine. Additionally, the study does not list the solution used as the "placebo." 

July 7, 2008 – United States District Court Southern District of New York Elizabeth Ohuche, Plaintiff, against Merck & Company, Inc., Defendant “Plaintiff alleges that on March 12, 2009, her primary care physician, Dr. Itkovitz, injected her against her will with ZOSTAVAX, a vaccine manufactured by Merck.  A '''''few days later, plaintiff  “developed severe headache, fever and high temperature.” Plaintiffs “condition escalated daily with excruciating pains followed by bumps, boils, and eruptions all over her face.” Plaintiffs “condition is accompanied with wicked clustered and painful rashes which are very difficult to treat” and recur with “more pains, headaches, fever, tingling and discomfort., Plaintiffs eyesight was also affected as she “lost partial sight at her right eye when the eruption occurred at her eyelid.” Plaintiff claims that ZOSTAVAX caused all of these adverse reactions. Plaintiff further claims that her condition has gotten worse over the past two years and that she is “very ill and confined in bed.” Plaintiff demands that Merck provide “a cure for her condition” and “compensate her for pains and suffering.”

March 6, 2008 – Varicella-Zoster Virus–Specific Immune Responses in Elderly Recipients of a Herpes Zoster Vaccine (full text) “The VZV-CMI responses at 6 weeks after vaccination decreased with age and were significantly lower in subjects ⩾70 years old compared to subjects 60–69 years old .”…”Assays were performed on aliquots of the same PBMC preparations tested in the RCF assay. They were shipped on dry ice to Merck Research Laboratories, West Point, Pennsylvania, where ELISPOT assays were performed.”…

March 2, 2008 – The Epidemiological, Clinical, and Pathological Rationale for the Herpes Zoster Vaccine (full text) “

January 15, 2008 – The shingles vaccine: Why hasn’t it caught on? “Maybe not a great deal after all. Merck is charging about $150 for the one-shot vaccineDoctors and hospitals charge a mark-up, so the total bill can come close to $300. In comparison, the standard flu vaccine costs between $11 and $15, and the pneumococcal vaccine, about $25. Traditionally, vaccines are one of the best health bargains out there — a low up-front cost that pays for itself many times over in averted sickness and early death. But vaccine costs are going up, so the economics aren’t so clear-cut anymore. A cost-effectiveness analysis of Zostavax published in the Annals of Internal Medicine in 2006 put it in the intermediate cost-effectiveness category.”

August 1, 2007 – Safety Of Shingles Vaccine Confirmed After One Year (full text) “A total of 590 reports related to Zostavax ('including 44 classified as serious) had been submitted as of June 1, 2007, to the Vaccine Adverse Event Reporting System (VAERS), a vaccine safety surveillance system operated by the CDC and the Food and Drug Administration. The overall reporting rate was 73.3/100,000 doses distributed, and the serious event reporting rate was 5.5/100,000 doses distributed. Two of the 44 serious events reported were deaths. Most (90%) of the reports referred to the Zostavax vaccine administered alone, and 82 reports involved possible off-label use or medical error.Comment: Off-label use of a shingles vaccine? 

July 2005 – Universal Varicella Vaccination: Efficacy Trends and Effect on Herpes Zoster (pdf) “The increase in vaccine efficacy from 86.7% in 1997 to 95.7% in 1999 (Table 2) was likely attributed to the additional residual boosting to vaccinees that resulted from contact with children having natural disease. In 1997 and 1998 the incidence of varicella was still high in the community and displayed the characteristic seasonality (Seward et al. 2002).”…”A few years after licensure of the varicella vaccine (on March 17, 1995) by the U.S. Food and Drug Administration (FDA) (Hardegree and Donlon 1995), physicians expressed concern that it was unknown if periodic reexposures to natural varicella in the community played a significant role in helping to suppress the reactivation of herpes zoster(HZ) (Spingarn and Benjamin 1998; Wack 1998). The universal varicella vaccination program, combined with mandates adopted in many states requiring school-entry children to be vaccinated, resulted in high coverage rates, allowing the concerns related to increasing HZ incidence to be investigated.”

June 16, 2005 – The incidence of varicella and herpes zoster in Massachusetts as measured by the Behavioral Risk Factor Surveillance System (BRFSS) during a period of increasing varicella vaccine coverage, 1998–2003 (full text) “As varicella vaccine coverage in children increased, the incidence of varicella decreased and the occurrence of herpes zoster increased. If the observed increase is real, widespread vaccination of children is only one of several possible explanations.”

June 12, 2005 Incidence of Herpes Zoster, Before and After Varicella-Vaccination-Associated Decreases in the Incidence of Varicella, 1992–2002(full text) “Exposure to varicella may afford protection against HZ. This postulation is supported by other studies [28, 29]; for example, Arvin et al. have reported that 71% of adults with household exposure to varicella experience a boost in cellular immune responses, and Gershon et al. have reported that vaccinated leukemic children who had household exposure to varicella were less likely to develop shingles than were those who did not have such exposure [29]. Yet, other issues—including factors that contribute to boosting, the duration of protection after exposure, and other factors influencing reactivation—remain to be investigated.

June 2002 Exposure to varicella boosts immunity to herpes-zoster: implications for mass vaccination against chickenpox“We present data to confirm that exposure to varicella boosts immunity to herpes-zoster. We show that exposure to varicella is greater in adults living with children and that this exposure is highly protective against zoster (Incidence ratio=0.75, 95% CI, 0.63–0.89).”