Safety profile of the adjuvanted recombinant zoster vaccine: Pooled analysis of two large randomised phase 3 trials

Background

The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was ≥90% efficacious in preventing herpes zoster in adults. Here we present a comprehensive overview of the safety data from these studies.

Status of vaccine research and development of vaccines for herpes simplex virus

Herpes simplex virus type-1 (HSV-1) and -2 (HSV-2) are highly prevalent global pathogens which commonly cause recurrent oral and genital ulcerations. Less common but more serious complications include meningitis, encephalitis, neonatal infection, and keratitis. HSV-2 infection is a significant driver of the HIV epidemic, increasing the risk of HIV acquisition 3 fold. As current control strategies for genital HSV-2 infection, including antiviral therapy and condom use, are only partially effective, vaccines will be required to reduce infection. Both preventive and therapeutic vaccines for HSV-2 are being pursued and are in various stages of development. We will provide an overview of efforts to develop HSV-2 vaccines, including a discussion of the clinical need for an HSV vaccine, and status of research and development with an emphasis on recent insights from trials of vaccine candidates in clinical testing. In addition, we will touch upon aspects of HSV vaccine development relevant to low and middle income countries.     

Recurrent herpes labialis in the pediatric population: Prevalence,therapeutic studies,and associated complications

Recurrent herpes labialis (RHL) is an incredibly common condition, though the medical literature evaluating pediatric aspects is limited. This paper assesses prevalence and therapeutic studies of pediatric RHL as well as disease complications. A comprehensive literature search of English‐language citations based on PubMed queries of selected terms was performed, with exclusion if methodology was not discussed, or if studies had 10 or fewer patients. RHL prevalence in pediatrics has been assessed by measures of point and periodic prevalence, though methodologic limitations may under‐ or over‐estimate the true prevalence of RHL. Studies have been conducted to evaluate therapeutic safety, tolerability, and efficacy of antivirals in the pediatric population. Pediatric RHL point prevalence ranges from 0.72% to 5.2% depending on the population study and the methodologies used. Pediatric RHL carries a significant public health burden and is often implicated in patients with eczema herpeticum, erythema multiforme, reactive infectious mucositis eruptions, and hypersensitivity reactions. There are few studies that evaluate the rates of occurrence of these sequelae associated with pediatric RHL.     

Herpes simplex virus latency in the nervous system – a new model

Permissive herpes simplex virus (HSV) infection in tissue culture results in host cell destruction. Latent HSV infection in vivo occurs in neurons of peripheral sensory ganglia (PSG) and it therefore can not take place in neurons in which the virus has completed a lytic replication cycle similar to that present in vitro. Our hypothesis, based on experimental data and observations in humans, suggests that establishment of latent infection and reactivation of HSV-1 does not involve neuronal cell loss. Latency is established in neurons in which the virus does not replicate and is determined, in part, by the tissue levels of a herpes transactivating protein (Vmw65) that is a component of the viral tegument. We also suggest that reactivation of latent infection does not involve destruction of neurons and is due to replication of virus at the peripheral mucocutaneous tissues to where virus or viral DNA have been transported from the nervous tissue. Alternatively, reactivation is initiated in the PSG using a replication cycle which does not involve irreversible damage to neurons. This model explains the lack of damage to neurons which continue to serve as permanent reservoirs of latent virus for the entire life of the host.     

不同剂量和疗程伐昔洛韦治疗带状疱疹的多中心随机双盲对照研究

目的：比较不同剂量和疗程伐昔洛韦治疗带状疱疹的疗效和安全性。方法：选择带状疱疹患者为研究对象，采用多中心、随机、双盲、对照的临床试验。试验组患者采用伐昔洛韦1000mg每日3次口服，共服7d；对照组患者采用伐昔洛韦300mg每日2次口服，共服10d。用药后第3、6和10天观察疗效和不良反应。结果：共入组128例，全分析集（FAS）分析128例，符合方案集（PPS）分析118例。治疗后第3、6和10天，试验组和对照组患者的症状、体征积分下降值及有效率比较差异无统计学意义（P〉0．05）；疼痛视觉模拟评分法（visnal analogue scale，VAS）值比较，两组间差异无统计学意义（P〉0．05），但入组时疼痛VAS值≥8的患者，FAS集分析显示，在治疗后第6、10天VAS值下降两组均存在统计学差异（P〈0．05）；PPS集分析显示治疗后第10天VAS值下降，两组间存在统计学差异俨〈0．05）。试验组和对照组不良反应发生率分别为17．18％和12．50％．主要为嗜睡和恶心。结论：增加伐昔洛韦用量治疗带状疱疹安全、有效，与较低剂量伐昔洛韦组相比，对疼痛程度较严重的患者能更显著地减轻疼痛。     

原发女性生殖道恶性黑色素瘤21例临床分析

目的探讨原发性女性生殖道恶性黑色素瘤的临床特点、治疗及预后。方法回顾分析本院1986年1月至2006年3月收治的原发性女性生殖道恶性黑色素瘤患者21例。其中外阴8例、阴道10例、阴道及宫颈1例、外阴及阴道1例、盆腔1例。结果患者中位年龄50(21~71)岁。临床表现主要为阴道流血、流液及发现外阴或阴道肿物。本资料阴道恶性黑色素瘤发病率高于外阴恶性黑色素瘤。按照国际妇产科联盟(FIGO)分期,期别和预后呈负相关。治疗以手术为主,手术方式由根治性切除逐渐衍变为扩大局部切除。随访:21例患者中随访率为67%(14/21),随访时间6~96个月,死亡7例,随访期间的死亡率为50%。结论女性生殖道恶性黑色素瘤发病率低,预后差。肿瘤厚度和淋巴结转移是其主要的危险因素。应采用手术基础上的综合治疗,治疗方案个体化。     

Oncolytic herpes viral therapy is effective in the treatment of hepatocellular carcinoma cell lines

The rising incidence of hepatocellular carcinoma (HCC) in western countries, along with the poor prognosis offered by present-day treatment modalities, makes novel therapies for this disease necessary. Oncolytic herpes simplex viruses (HSV) are replication-competent viruses that are highly effective in the treatment of a wide variety of experimental models of human malignancies. This study seeks to investigate the effectiveness of oncolytic herpes viruses in the treatment of primary HCC cell lines. Sixteen commercially available human HCC cell lines were studied. G207 is an attenuated, replication-competent, oncolytic HSV engineered to selectively replicate within cancer cells. Cell lines were tested for viral sensitivity to G207 and their ability to support viral replication using standard cytotoxicity and viral replication assays. Eleven of 16 cell lines were moderately to highly sensitive to G207 viral oncolysis. HCC cell lines additionally demonstrated the ability to support viral replication in vitro with as high as 800-fold amplification of the administered viral dose observed. G207 is cytotoxic to, and efficiently replicates within, HCC cell lines in vitro. From these data, we suggest that oncolytic HSV therapy may have a role in the treatment of HCC, and in vivo studies are warranted. Presented in part at the 2005 American Hepato-Pancreato-Biliary Association Congress, Hollywood, Florida, April 14–17, 2005. Supported by grants R01CA75461 and R01CA72632 from the National Institutes of Health, and by grant MBC-99366 from the American Cancer Society (Yuman Fong).