Zostavax: a subcutaneous vaccine for the prevention of herpes zoster

Introduction: Herpes zoster (HZ) occurs as a reactivation of dormant varicella zoster virus (VZV), and occurs more frequently in the aging population or the immunocompromised due to waning cell-mediated immunity. Up to 1 million cases of HZ are reported annually in the USA with an estimated 10 – 30% of the population being affected by shingles in their lifetime. HZ is a debilitating illness, and while mortality is low, morbidity remains a significant cause for concern with prevention efforts aimed at reducing VZV reactivation and its complications. The HZ vaccine was approved by the US Food and Drug Administration for individuals aged 50-years or older. However, the Center for Disease Control and Prevention's Advisory Committee for Immunization Practices recommends the vaccine in individuals aged 60-years or older.

Areas covered: Recent literature investigating the efficacy and indications of live attenuated zoster vaccine.

Expert opinion: Live attenuated zoster vaccine is safe and efficacious in preventing HZ and decreasing the morbidity associated with postherpetic neuralgia. The vaccine is FDA approved in individuals aged 50-years or older but further studies are warranted to investigate the vaccine's efficacy in immunosuppressed and immunocompromised patients.     

Herpes zoster vaccine (Zostavax)

A live attenuated varicella-zoster vaccine (Zostavax--Merck) has been approved by the FDA for prevention of herpes zoster (HZ; zoster; shingles) in persons > or = 60 years old. Each dose of Zostavax contains about 14 times as much varicella-zoster virus (VZV) as Varivax, which has been used in the US since 1995 to vaccinate against varicella (chicken pox).     

Herpes Zoster Meningitis in a Young,Immunocompetent Adult

BackgroundVaricella-zoster virus is typically encountered in the emergency department (ED) in two forms: varicella (chickenpox) in children and zoster (shingles) in older adults. Zoster is infrequently encountered in young, healthy adults, and neurological complications are extremely rare.Case ReportWe describe a case of a previously healthy 36-year-old woman who presented to the ED with fever, nuchal rigidity, and headache 4 days after being diagnosed with herpes zoster and started on oral valacyclovir. Lumbar puncture confirmed herpes zoster meningitis. Despite initiation of antivirals within 48 h of symptom onset, progression to zoster meningitis occurred.Why Should an Emergency Physician Be Aware of This?Emergency physicians must be aware that neurological complications of varicella zoster can develop despite initiation of oral antivirals. These patients must be identified in the ED, as admission for intravenous antivirals is indicated.     

Herpes Zoster Immunization in Older Adults Has Big Benefits

A case of acute herpes zoster neuralgia (shingles) in a 78-year-old patient is described. The value and importance of immunizing against herpes zoster to decrease the incidence and severity of both acute herpes zoster neuralgia and postherpetic neuralgia are described.

This report is adapted from paineurope 2015: Issue 1, ©Haymarket Medical Publications Ltd., and is presented with permission. paineurope is provided as a service to pain management by Mundipharma International, Ltd., and is distributed free of charge to health care professionals in Europe. Archival issues can be viewed via the Web site: www.paineurope.com, at which health professionals can find links to the original articles and request copies of the quarterly publication and access additional pain education and pain management resources.     

Vaccination of autologous stem cell transplant recipients with live varicella vaccine: a pilot study

A pilot study of vaccination with live, attenuated varicella vaccine for prevention of zoster was performed in autologous stem cell transplant (SCT) recipients. Nine patients were vaccinated between 3–4 months after transplantation. The antigen-specific immune response was studied by lymphocyte proliferation. No systemic side effects were seen. One of nine patients developed herpes zoster HZ during follow-up. There was a tendency for a strengthened specific immune response after SCT (p=0.12). This pilot study shows that vaccination with live, attenuated varicella vaccine can be performed safely 3–4 months after autologous stem cell transplantation. Additional studies are needed to assess efficacy of this approach in the prevention of HZ.     

Recombinant Zoster Vaccine (Shingrix) to Prevent Herpes Zoster

Women ages 50 years and older are at risk for herpes zoster, a reactivated virus from varicella zoster virus (chickenpox) that causes a painful vesicular rash and can result in postherpetic neuralgia. It is estimated that one in three adults will be affected by herpes zoster in their lifetime. Research evidence points to the need to prevent herpes zoster through vaccination. Since 2006, clinicians have been vaccinating adults with zoster vaccine live (brand name Zostavax), but the efficacy of this vaccine wanes with time and advanced age. In October 2017, the U.S. Food and Drug Administration approved recombinant zoster vaccine under the brand name Shingrix to prevent herpes zoster. Studies have shown significantly better efficacy of Shingrix versus Zostavax. This article summarizes new guidance regarding vaccination with Shingrix and discusses implications for women’s health.     

Improving rates of herpes zoster vaccination with a clinical decision support system in a primary care practice

Rationale Herpes zoster (shingles) is a localized neurocutaneous eruption of blisters caused by reactivation of the varicella zoster virus. The cost of care for herpes zoster and its complications is estimated at $1.1 billion. The Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices recommends a one‐time dose of the vaccine for adults aged 60 years or older. Despite that recommendation, utilization of the vaccine is very low. One way to boost the delivery of preventive services such as vaccinations is with a computerized clinical decision support system. Our study found that the herpes zoster vaccination rate increased significantly after the implementation of such a system. Aims To study utilization of herpes zoster vaccine before and after the implementation of a web‐based clinical decision support software solution in a primary care practice. Methods Billing data was utilized to determine number of herpes zoster vaccination administered to patients for a 12‐month period during the implementation of the software solution. Results The utilization of vaccinations improved from 63 to 117 (53.8% increase) for one primary care practice and from 54 to 127 (42.5% increase) in the other primary care practice. Conclusion Herpes zoster vaccination rate significantly improved with implementation of a web‐based clinical decision support system.     

Herpes Zoster Immunization in Older Adults Has Big Benefits

The value and importance of providing herpes zoster immunization to reduce the incidence and severity of acute herpes zoster neuralgia, especially in older patients, is described. The prevention of postherpetic neuralgia can profoundly impact patients’ quality of life.

This report is adapted from paineurope 2014; Issue 4, © Haymarket Medical Publications Ltd, and is presented with permission. paineurope is provided as a service to pain management by Mundipharma International, LTD and is distributed free of charge to healthcare professionals in Europe. Archival issues can be viewed via the website: www.paineurope.com at which health professionals can find links to the original articles and request copies of the quarterly publication and access additional pain education and pain management resources.     

Improved outlook on HIV-1 prevention and vaccine development

Introduction: The development of an effective vaccine against HIV-1 has been challenging but recent advances in both the HIV prevention landscape and the partial efficacy of the recent RV144 vaccine efficacy trial in Thailand provide hope for an improved arsenal of approaches to prevent HIV-1 transmission.

Areas covered: This review describes recent advances in HIV-1 prevention such as circumcision, microbicides and pre-exposure prophylaxis with antiretroviral therapy, but focuses mainly on the current state of HIV-1 vaccine development in the post-RV144 era.

Expert opinion: The field of HIV-1 vaccine development has been plagued by the unprecedented challenges involved with designing a vaccine effective in preventing transmission of a retrovirus, due in part to sequence diversity, retroviral integration into host chromosomes, establishment of reservoir sites and glycosylation shielding of the HIV-1 envelope. The partial efficacy of the recent RV144 vaccine trial in Thailand may allow for better understanding of immune correlates of infection risk, which could enable iterative improvements to vaccine regimens in the development pipeline. In parallel, a number of promising vaccine strategies incorporating viral vectors, novel immunogens, delivery systems and adjuvants are advancing in clinical development. Vaccine development must occur in parallel with continued advances in HIV-1 prevention.     

Herpes Zoster Pain,Postherpetic Neuralgia,and Quality of Life in the Elderly

Herpes zoster pain and postherpetic neuralgia (PHN) particularly affect older persons. This literature review presents how quality of life is evaluated and the consequences of shingles and PHN on the quality of life of older persons. Although more than 150 articles have been published on herpes zoster and its consequences, specific studies focusing on the older population are needed, in several domains like epidemiology, preventive medicine, neuropsychology, and pharmacology.     

Immunomodulatory properties of vitamins,flavonoids and plant oils and their potential as vaccine adjuvants and delivery systems

Introduction: During the past century, vaccinologists have attempted to mimic pathogens in their immune-enhancing capacity. This led to the development of life-saving vaccines based on live attenuated viruses, bacteria and toxoids. Hence, intense research in vaccine adjuvant discovery has focused on toll like receptors, mutant toxins and viral and bacterial vectors. Nutritive components such as vitamins and select polyphenols also possess immunomodulating properties without the potential toxic and adverse side effects of agents that mimic danger signals.

Areas covered: This review pertains to immunomodulatory properties of nutritive components, that is vitamins A, C, D, E, flavonoids and plant oils, as potential vaccine adjuvants and delivery systems, covering Pubmed publication searches from 1980 through 2011.

Expert opinion: This relatively unexplored field of the potential of nutritive components as vaccine adjuvants holds great promise to promote the development of effective and above all safe vaccines. Hence the future focus should be placed on enhancing their efficacy, mainly through novel approaches in designing structural derivatives, formulations, delivery systems and routes of administration. As safety has been the major issue in development of novel vaccines, this new approach will probably result in new discoveries in designing safe and effective vaccines.     

Zoster vaccine to prevent postherpetic neuralgia

In 2006, the U.S. Food and Drug Administration approved the first vaccine for the prevention of acute herpes zoster neuralgia (shingles). This vaccine has important implications in reducing the incidence and severity of the common neuropathic pain condition postherpetic neuralgia. The new vaccine is described.     

An update on vaccines for tuberculosis – there is more to it than just waning of BCG efficacy with time

Introduction: Apart from better diagnostics and new anti-microbial drugs, an effective vaccine for tuberculosis is urgently needed to halt this poverty-related disease, afflicting millions of people worldwide.

Areas covered: After a general introduction on the global threat of tuberculosis, the pros and cons of the existing M. bovis BCG vaccine are discussed. As the correlates of protection against tuberculosis remain largely unknown, new findings in biomarker research are described. Next, an update on the ongoing Phase I and Phase II clinical trials is given. Finally, some of the most promising novel pre-clinical developments using live attenuated vaccines, sub-unit vaccines, prime-boost strategies, and new vaccination routes are discussed. The field has made considerable progress and 12 vaccine candidates have now actually entered Phase I or Phase IIa and IIb clinical trials.

Expert opinion: It is argued that the variable protection conferred by the existing BCG vaccine against reactivation of latent TB is caused not only by waning of its efficacy with time but also by its weak induction of MHC class I restricted responses. Prime-boost strategies based on the actual BCG vaccine may not be sufficient to overcome this hurdle. The use of plasmid DNA vaccination might offer a solution.     

Updates in Adult Immunizations

The Advisory Committee on Immunization Practices (ACIP) recommends that adults aged ≥19 years receive various vaccines to prevent serious health conditions, including hepatitis B, herpes zoster/shingles, human papilloma virus (HPV), and pneumonia. Recent vaccine approvals by the US Food and Drug Administration (FDA) have led to updates in the ACIP adult immunization schedule. This article provides a relevant clinical literature review for nurse practitioners on the newly approved vaccines for hepatitis B and herpes zoster and updated ACIP recommendations. In addition, recent FDA approval for expanded age of the HPV vaccine and updated ACIP recommendations for pneumococcal vaccines are discussed.     

The development of 13-valent pneumococcal conjugate vaccine and its possible use in adults

Introduction: Worldwide, Streptococcus pneumoniae causes significant morbidity and mortality. The 23-valent pneumococcal polysaccharide vaccine (PPSV23) has been recommended for use in persons aged 65 years and over and in adults with certain chronic medical conditions. Pneumococcal conjugate vaccines (PCVs) have been developed for use in infants and children aged less than 5 years, and are being studied for use in adult populations.

Areas covered: The different types of pneumococcal vaccines are discussed. Studies comparing PPSV23 and PCVs, as well as the results of the widespread use of 7-valent PCV are covered. The possible extension of the use of 13-valent PCV to adults, particularly to vulnerable populations, is discussed. The MEDLINE database was used to identify relevant studies from literature published in English between January 1977 and January 2011. All studies of adults aged over 18 years were considered for the review.

Expert opinion: Elderly individuals and adults with chronic medical conditions who are at increased risk for pneumococcal disease would benefit from more effective prevention than is provided by the currently recommended PPSV23.     

The virosomal adjuvanted influenza vaccine

Importance of the field: The protection conferred by influenza vaccines varies for several reasons, for example the age or degree of immune depression of the recipient. All currently available seasonal influenza vaccines are safe and substantially effective in preventing influenza in healthy people. However, elderly people and patients with chronic diseases or immune system defects need a more effective vaccine to avoid serious risks from influenza and its complications. Research has been undertaken to improve the efficacy of vaccination. Recent research includes the use of new adjuvants or antigen-presenting strategies.

Areas covered in this review: The virosomal adjuvanted subunit influenza vaccine has been studied in groups for whom vaccination is recommended. We describe virosomal technology, including production and mode of action, as well as the available efficacy, immunogenicity and safety data, with the aim of understanding the benefits of this vaccine's use.

What the reader will gain: A review of published data on efficacy, immunogenicity and safety from sponsor- and investigator- driven studies, focusing on recent publications.

Take home message: The vaccine was generally very immunogenic and safe in all investigated populations. Its ability to induce protective antibody titers has been shown to exceed that of conventional influenza vaccines in elderly people and individuals with little or no prior exposure to the viral strains.     

MF59-adjuvanted vaccine: a safe and useful tool to enhance and broaden protection against seasonal influenza viruses in subjects at risk

Importance of the field: Vaccination is universally considered as the most effective tool for the prevention of influenza, which represents a significant burden, both from a health-care and a socio-economic viewpoint. Conventional non-adjuvanted vaccines have shown suboptimal immunogenicity in the elderly, in patients with serious chronic diseases or the immunocompromised and in young children. The protection offered by non-adjuvanted vaccines may be further reduced by periodic antigenic drifts.

Areas covered in this review: Between the several strategies proposed to address the need for more immunogenic vaccines than the conventional ones, the most successful strategy is represented by the use of adjuvants. Since 1997, an MF59-adjuvanted subunit influenza vaccine has been licensed in several countries and used in the elderly worldwide. Available data on the safety, immunogenicity and effectiveness of this vaccine have been reported and discussed in details.

What the reader will gain: The MF59-adjuvanted vaccine has been shown to enhance immunogenicity and to confer cross-reactivity against heterologous influenza viral strains in the elderly, in adults with serious underlying medical conditions and in healthy infants and young children. Furthermore, its effectiveness has been demonstrated in older adults, reducing hospitalizations for pneumonia, cardiovascular and cerebrovascular diseases.

Take home message: The vaccine is safe, with an acceptable tolerability profile, thus representing a valid option to optimize the control of seasonal influenza.     

Reassessing the link between herpes zoster ophthalmicus and stroke

This editorial will assess a proposed link between herpes zoster ophthalmicus and subsequent stoke. Herpes zoster (also called shingles) is caused by varicella-zoster virus (VZV), one of the 9 human herpesviruses. When children contract their primary VZV infection, virus often travels to the trigeminal ganglia and establishes latency. Upon reactivation in late adulthood, the same virus travels anterograde to cause herpes zoster ophthalmicus. In some people, the virus also traffics from the same trigeminal ganglion along afferent fibers around the carotid artery and its branches. Subsequently VZV-induced inflammation within the affected cerebral arteries leads to occlusion and stroke. In one retrospective analysis of people with herpes zoster ophthalmicus, there was a 4.5 fold higher risk of stroke than in a control group. Two other studies found a less compelling association.     

Herpes simplex virus oncolytic vaccine therapy in melanoma

Importance of the field: Advanced melanoma is a devastating disease with a five year survival for Stage IV disease of 10 – 20% and a median survival of 6 – 18 months depending on sub-stage. Current FDA approved therapies demonstrate limited response rates, few complete remissions and no proven survival benefit. New therapies are clearly needed. JSI/34.5-/47-/GM-CSF is a herpes simplex virus-1 (OncoVEX^GM-CSF) oncolytic vaccine therapy designed to induce local and systemic anti-tumor immune responses.

Areas covered in this review: Evolution of current herpes simplex virus oncolytic vaccines from preclinical to clinical studies from 1994 to 2010.

What the reader will gain: Preclinical studies have shown that herpes simplex virus-1 oncolytic vaccines generate local tumor destruction through the lytic action of the virus and local and systemic immune responses. Phase I studies demonstrated limited toxicities with no neurotoxicty. Phase II studies demonstrated durable regressions in patients with metastatic melanoma. A Phase III trial in melanoma is ongoing to determine clinical effectiveness, and a Phase III trial in head and neck cancer will initiate during 2010.

Take home message: JSI/34.5-/47-/GM-CSF is a new generation herpes simplex virus-1 oncolytic vaccine that demonstrates direct tumor lysis and systemic immune responses. Early clinical studies have yielded preliminary evidence of activity.     

Transverse myelitis after infection with varicella zoster virus in patient with normal immunity: A case report

BACKGROUNDVaricella zoster virus (VZV) is a human neurotropic and double-stranded DNA alpha-herpes virus. Primary infection with VZV usually occurs during childhood, manifesting as chickenpox. Reactivation of latent VZV can lead to various neurological complications, including transverse myelitis (TM); although cases of the latter are very rare, particularly in newly active VZV infection.CASE SUMMARYWe report here an unusual case of TM in a middle-aged adult immunocompetent patient that developed concomitant to an active VZV infection. The 46-year-old male presented with painful vesicular eruption on his left chest that had steadily progressed to involvement of his back over a 3-d period. Cerebrospinal fluid testing was denied, but findings from magnetic resonance imaging and collective symptomology indicated TM. He was administered antiviral drugs and corticosteroids immediately but his symptom improvement waxed and waned, necessitating multiple hospital admissions. After about a month of repeated treatments, he was deemed sufficiently improved for hospital discharge to home.CONCLUSIONVZV myelitis should be suspected when a patient visits the outpatient pain clinic with herpes zoster showing neurological symptoms.