Vaccine prevents genital herpes in subgroup of women

The herpes simplex virus (HSV) type-2 vaccine studied here prevented genital herpes only in women who were seronegative for HSV-1 and HSV-2 at baseline. Ten of these women would need to be vaccinated to prevent 1 case of genital herpes. The vaccine did not prevent infection with HSV-2 in these women. It did not prevent genital herpes in women with other HSV serologic status or in men. The usefulness of this vaccine is limited by the small subgroup in which it is efficacious. Determining which women fall into this subgroup could prove costly. It is possible that asymptomatic infected persons may spread HSV more readily. Emphasis on the use of condoms and antiviral agents should still be the first line in preventing the spread of genital herpes.     

青岛地区不同职业人群中生殖器单纯疱疹病毒感染情况的流行病学调查

在青岛地区对随机抽查的１１个不同职业及两个特殊人群（妊娠、宫颈癌）中１１４８份生殖器分泌物，应用单克隆抗体双夹心法酶联免疫吸附试验（ＭｃＡｂ－ＥＬＩＳＡ），分型检测标本中单纯疱疹病毒（ＨＳＶ）抗原，总阳性一率为２２．６％，其中ＨＳＶ－１占２０．０％。在不同性别中，男性标本中ＨＳＶ抗原阳性率２４．２％，女性为２１．５％，两者无显著性差异。特殊职业，反途贩运司标本中，ＨＳＶ抗原阳性率为４８．０％，个体     

Protection against herpes simplex virus type 2 infection in a neonatal murine model using a trivalent nucleoside-modified mRNA in lipid nanoparticle vaccine

Neonatal herpes is a dreaded complication of genital herpes infection in pregnancy. We recently compared two vaccine platforms for preventing genital herpes in female mice and guinea pigs and determined that HSV-2 glycoproteins C, D and E expressed using nucleoside-modified mRNA in lipid nanoparticles provided better protection than the same antigens produced as baculovirus proteins and administered with CpG and alum. Here we evaluated mRNA and protein immunization for protection against neonatal herpes. Female mice were immunized prior to mating and newborns were infected intranasally with HSV-2. IgG binding and neutralizing antibody levels in mothers and newborns were comparable using the mRNA or protein vaccines. Both vaccines protected first and second litter newborns against disseminated infection based on virus titers in multiple organs. We conclude that both vaccines are efficacious at preventing neonatal herpes, which leaves the mRNA vaccine as our preferred candidate based on better protection against genital herpes.     

Neonatal herpes simplex virus infection in the British Isles

Summary. This study was set up to estimate the incidence of neonatal herpes simplex virus (HSV) infection in the British Isles, and to document the outcome of neonatal infection. Paediatricians reported cases of neonatal HSV through the active reporting scheme of the British Paediatric Association Surveillance Unit. Over a 5half year period (1986-91) 76 infants with neonatal HSV infection were reported, an incidence of recognised infection in the British Isles of 1.65/100000 livebirths. Twenty-five infants had HSV-1 infection, 24 HSV-2 and in 27 virus type was unknown. Twenty-seven had disseminated infection, 23 herpes encephalitis and 26 localised infection. Nineteen infants (25%) died in the neonatal period, and a further 25 (33%) have subsequently died or have long-term sequelae. At least half of the infants had been discharged home before symptoms became apparent. For 21 women there was evidence of a maternal genital herpes infection at some time, but this was reported or diagnosed retrospectively after neonatal HSV was suspected in 19 cases, and ante-natally in only two. Neonatal HSV is rare in the British Isles and routine antenatal screening for genital herpes infection during pregnancy is not justified. A high proportion of infected infants present with non-specific signs and symptoms and without mucocutaneous involvement; furthermore, there is rarely a history of maternal infection. As early diagnosis and prompt treatment is essential, there must be a high level of awareness of the serious nature of neonatal HSV infection.     

Biologic interactions between HSV-2 and HIV-1 and possible implications for HSV vaccine development

Development of a safe and effective vaccine against herpes simplex virus type 2 (HSV-2) has the potential to limit the global burden of HSV-2 infection and disease, including genital ulcer disease and neonatal herpes, and is a global sexual and reproductive health priority. Another important potential benefit of an HSV-2 vaccine would be to decrease HIV infections, as HSV-2 increases the risk of HIV-1 acquisition several-fold. Acute and chronic HSV-2 infection creates ulcerations and draws dendritic cells and activated CD4+ T cells into genital mucosa. These cells are targets for HIV entry and replication. Prophylactic HSV-2 vaccines (to prevent infection) and therapeutic vaccines (to modify or treat existing infections) are currently under development. By preventing or modifying infection, an effective HSV-2 vaccine could limit HSV-associated genital mucosal inflammation and thus HIV risk. However, a vaccine might have competing effects on HIV risk depending on its mechanism of action and cell populations generated in the genital mucosa. In this article, we review biologic interactions between HSV-2 and HIV-1, consider HSV-2 vaccine development in the context of HIV risk, and discuss implications and research needs for future HSV vaccine development.     

Pandemic (H1N1) 2009 Surveillance for Severe Illness and Response, New York, New York, USA, April�CJuly 2009

On April 23, 2009, the New York City Department of Health and Mental Hygiene (DOHMH) was notified of a school outbreak of respiratory illness; 2 days later the infection was identified as pandemic (H1N1) 2009. This was the first major outbreak of the illness in the United States. To guide decisions on the public health response, the DOHMH used active hospital-based surveillance and then enhanced passive reporting to collect data on demographics, risk conditions, and clinical severity. This surveillance identified 996 hospitalized patients with confirmed or probable pandemic (H1N1) 2009 virus infection from April 24 to July 7; fifty percent lived in high-poverty neighborhoods. Nearly half were <18 years of age. Surveillance data were critical in guiding the DOHMH response. The DOHMH experience during this outbreak illustrates the need for the capacity to rapidly expand and modify surveillance to adapt to changing conditions.     

Incidence of herpes neonatorum in Netherlands

OBJECTIVE: Investigation of the incidence of neonatal herpes in the Netherlands between 1992 and 1998. DESIGN: Inventory questionnaire survey. METHODS: All virological laboratories in the Netherlands were sent a questionnaire on the number of culture proven cases of neonatal herpes recorded between 1992 and 1998 and on the type of herpes simplex virus (HSV-1 or HSV-2). The gynaecological and paediatric departments of all university hospitals and of half of the general hospitals were sent questionnaires as well. Gynaecologists were asked how often caesarean section was performed in order to prevent neonatal herpes and how frequently pregnant women were seen with genital herpes. Paediatricians were asked how often they observed neonatal herpes, the type of HSV and the possible transmission route. Based on these data the figures for the whole of the Netherlands were estimated. RESULTS: The incidence of neonatal herpes in the Netherlands in the period 1992 to 1998 was 2.4 per 100,000 neonates. HSV-1 was the cause of neonatal herpes in 73%, HSV-2 in 9%, and in 18% of the cases the type of infection was not recorded. The number of pregnant women with genital herpes had increased, but, in agreement with a consensus statement, the gynaecologists hardly performed caesarean sections any more to prevent neonatal herpes (2 per year). CONCLUSIONS: The incidence of neonatal herpes in the Netherlands had not increased. There was no predominant role of HSV type 2 causing neonatal herpes.     

Effect of immunization with herpes simplex virus type-1 (HSV-1) glycoprotein D (gD) plus the immune enhancer GPI-0100 on infection with HSV-1 or HSV-2

These studies were performed to determine the effects of GPI-0100, a semi synthetic Quillaja Saponin analog, formulated with herpes simplex virus type-1 (HSV-1) glycoprotein D (gD) on immunity to HSV. SKH-1 hairless mice, used as a model of herpes labialis, inoculated with HSV-1 results in facial lesions, virus replication and mortality. Mortality rates, lesion scores and viral titers were significantly reduced in SKH-1 mice immunized with gD/GPI-0100 prior to cutaneous inoculation with HSV-1 and the protective effects were greater than those using the standard alum adjuvant. Genital HSV-2 infections in guinea pigs were also utilized to determine if gD combined with GPI-0100 was protective against infection, disease severity and viral shedding. Guinea pigs immunized with HSV-1 gD with or without GPI-0100 had significantly reduced area under the curve lesion scores, but infection rates and virus shedding was not altered. When Tween 40 was added to gD and GPI-0100, mean peak lesion scores were also significantly reduced. The results obtained in a genital HSV-2 infection of guinea pigs did not indicate enhanced protection or reduced virus shedding following immunization with GPI-0100 and gD. There was, however, a significant improvement in clinical herpetic genital disease with the combination of gD plus the immune enhancer GPI-0100.     

Prevalence of antibodies to herpes simplex virus types 1 and 2 in pregnant women, and estimated rates of infection.

There has been a recent increase in notifications of genital herpes but it is not known whether this has been reflected in the pregnant population. We have therefore carried out a study to determine the prevalence of herpes simplex antibodies in pregnant women and to estimate the incidence of primary infection. Sera were collected from 3533 women at antenatal clinics and tested for total antibodies to herpes simples virus (HSV), and if positive, for specific antibodies to HSV-2. Estimates of HSV-1 seroprevalence were derived from the HSV-2 seronegative population. HSV-1 seroprevalence was nearly 100% in black women born in Africa or the Caribbean and 60-80% in white, Asian and UK born black women. It was lower in women in non-manual employment. HSV-2 seroprevalence was related to age, rising from 0 at age 16 to 40% at age 35 in black women, and to about 10% in Asian and white women. The estimated incidence of primary HSV-2 infection during pregnancy, per 1000 pregnancies, was about 2.4 in Asian women, 5 in white women, and 20 in black women. Estimates of the incidence of neonatal infection were derived from these figures and compared to the nationally reported rates.     

Genital herpes vaccines--cause for cautious optimism

The high prevalence of herpes simplex virus infections in many communities, its numerous serious physical and psychological complications and its importance in enhancing the transmission of HIV make this virus an obvious target for prevention by vaccination. Randomised clinical trials of only one genital herpes vaccine has shown efficacy so far. Analysis of clinical results is complicated by the difference between disease and infection, different results for males and females and the interaction between HSV-1 and HSV-2 immunity.     

An epidemiologic study of herpes simplex virus type 1 and 2 infection in Japan based on type-specific serological assays.

A seroepidemiologic study of herpes simplex virus type 1 (HSV-1) and 2 (HSV-2) was performed on Japanese adults. Serum samples collected between 1985-9 from a total of 536 healthy adults, female prostitutes, males with sexually transmitted diseases (STD), homosexual men, and pregnant women were studied by immunodot assays using HSV type-specific antigens, glycoproteins G (gG1 and gG2). HSV-1 infections correlated mostly with age and was widely prevalent among subjects < 40 years. HSV-2 prevalence varied greatly among subgroups defined by sexual activity and was associated with risk behaviours for prostitution, infection with STD, and homosexual activity. HSV-2 seroprevalence was highest among prostitutes (80%), lowest among pregnant women (7%), and intermediate in STD patients (23%) and homosexuals (24%). Because HSV-1 infection during childhood has been decreasing, primary genital HSV-2 infection, with its higher frequency of clinical manifestations, will become a greater burden to the public health in Japan.     

A randomized controlled trial of a replication defective (gH deletion) herpes simplex virus vaccine for the treatment of recurrent genital herpes among immunocompetent subjects

BACKGROUND: A replication incompetent herpes virus lacking the glycoprotein H gene has been developed as a potential therapeutic vaccine for genital herpes. GOAL: To determine vaccine efficacy on reducing HSV reactivation and clinical disease among immunocompetent persons with recurrent genital HSV-2 infection. STUDY DESIGN: Randomized multicenter placebo-controlled trial. Healthy volunteers who had six or more recurrences of genital herpes per year were randomized to receive injections of vaccine at 0 and 8 or 0, 4, and 8 or 0, 2, 4, and 8 weeks or placebo and were followed for subsequent recurrences for 1 year. RESULTS: The median times to first recurrence of genital herpes (40 days versus 30 days versus 37 days versus 42 days, respectively), mean number of recurrences (3 versus 3 versus 2.4 versus 1.9, respectively), and time to lesion healing of the first recurrence (8 days versus 7.8 days versus 7.4 days versus 7.5 days, respectively), were similar for all treatment groups. Asymptomatic viral shedding was detected by PCR in 61/74 (82%) persons performing daily sample collection following completion of the vaccination series. No differences were noted in the proportion of days with shedding between treatment groups (11.9% versus 17.2% versus 13.1% versus 16.4%, respectively). CONCLUSION: This replication incompetent HSV-2 vaccine lacking the glycoprotein H gene was safe but had no clinical or virologic benefit in the amelioration of genital HSV-2 disease among immunocompetent men and women.     

The challenges and opportunities for the development of a T-cell epitope-based herpes simplex vaccine

Herpes simplex virus type 1 and type 2 (HSV-1 & HSV-2) infections have been prevalent since the ancient Greek times. To this day, they still affect a staggering number of over a billion individuals worldwide. HSV-1 infections are predominant than HSV-2 infections and cause potentially blinding ocular herpes, oro-facial herpes and encephalitis. HSV-2 infections cause painful genital herpes, encephalitis, and death in newborns. While prophylactic and therapeutic HSV vaccines remain urgently needed for centuries, their development has been difficult. During the most recent National Institute of Health (NIH) workshop titled “Next Generation Herpes Simplex Virus Vaccines: The Challenges and Opportunities”, basic researchers, funding agencies, and pharmaceutical representatives gathered: (i) to assess the status of herpes vaccine research; and (ii) to identify the gaps and propose alternative approaches in developing a safe and efficient herpes vaccine. One “common denominator” among previously failed clinical herpes vaccine trials is that they either used a whole virus or a whole viral protein, which contain both “pathogenic symptomatic” and “protective asymptomatic” antigens and epitopes. In this report, we continue to advocate developing “asymptomatic” epitope-based sub-unit vaccine strategies that selectively incorporate “protective asymptomatic” epitopes which: (i) are exclusively recognized by effector memory CD4⁺ and CD8⁺ T cells (T_EM cells) from “naturally” protected seropositive asymptomatic individuals; and (ii) protect human leukocyte antigen (HLA) transgenic animal models of ocular and genital herpes. We review the role of animal models in herpes vaccine development and discuss their current status, challenges, and prospects.     

Laboratory investigations of herpes simplex virus-1 and -2 clinical samples in Korea

ObjectivesHerpes simplex virus (HSV) infections have been reported in 60% to 95% of the adult population worldwide, making them one of the most common infectious conditions globally. HSV-1 and HSV-2 cause severe disease in immunocompromised patients. Therefore, the aim of this study was to provide information that could be used to reduce the incidence of genital herpes caused by HSV-1 and HSV-2.MethodsFrom September 2018 to December 2020, 59,381 specimens were collected from outpatients across primary and secondary hospitals in Korea who requested U2Bio (Korea) to conduct molecular biological testing of their samples for sexually transmitted infections. In this study, the positivity rates of HSV-1 and HSV-2 were analyzed according to age, sex, and specimen type.ResultsIn the age-specific analysis of HSV-1, the highest positivity rate (0.58%) was observed in patients under 19 years of age, whereas the lowest positivity rate (0.08%) was observed in patients aged over 70 years. In the age-specific analysis of HSV-2, the highest positivity rate (2.53%) was likewise observed in patients under 19 years of age.ConclusionOur study identified differences in the infection rates of HSV-1 and HSV-2 depending on patients’ sex and age. These differences will be useful for improving disease prevention and control measures for HSV-1 and HSV-2.     

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.     

荧光PCR法检测2008年-2017年单纯疱疹病毒Ⅱ型感染的临床结果与分析

目的了解浙江地区疑似生殖器疱疹患者单纯疱疹病毒Ⅱ型(HSV-Ⅱ)感染情况,为临床诊断治疗提供依据。方法实时荧光PCR法对浙江省人民医院2008年-2017年2 230例疑似泌尿生殖道疱疹患者进行HSV-Ⅱ核酸检测。结果在2 230例疑似泌尿生殖道疱疹患者中,女性1 554例,男性676例,共检测出HSV-Ⅱ型阳性557例,阳性率为24.98%。557例HSV-Ⅱ感染患者中女性405例,阳性率为26.06%;男性152例,阳性率为22.49%,男、女感染率差异无统计学意义(P> 0.05)。557例HSV-Ⅱ型阳性患者分5个年龄段即<20岁、20岁~29岁、30岁~39岁、40岁~49岁、≥50岁分析,阳性率分别为3.05%、42.01%、29.80%、14.72%、10.23%。结论泌尿生殖道HSV-Ⅱ感染检出率较高,提示临床需重视对疑似生殖道疱疹病毒感染患者进行HSV-Ⅱ核酸检测;HSV-Ⅱ感染无性别差异,但感染主要集中在20岁~29岁患者。实时荧光PCR法在HSV-Ⅱ检测中具有快速、灵敏度高、简便等优点,适用于临床检测。     

杭州市一株单纯疱疹2型病毒株的分离鉴定

目的 建立一种能够对样本中的单纯疱疹病毒(Hsv)进行准确鉴定分型的方法,并从生殖器疱疹(GH)患者皮损的水疱液中分离出1株HSV-2.方法 从1例GH患者病变部位采集样本,样本接种Vero-E6细胞,待出现细胞病变后收获病毒感染物,提取病毒感染物的基因组.根据特异性PCR对分离出的病毒进行分型鉴定.结果 分离的毒株引起Vero-E6典型细胞病变,病变细胞圆缩、融合.型特异性PCR反应及l%琼脂糖凝胶电泳鉴定结果表明,扩增出的片段大小约为183 bp,与预期的HSV-2型特异性片段长度相符,且与数据库的比对结果显示相似性为100%.结论 通过细胞分离培养和特异性PCR分型鉴定,能够实现对样本中的HSV的准确分型鉴定.     

Immunotherapeutic activity of a recombinant combined gB-gD-gE vaccine against recurrent HSV-2 infections in a guinea pig model

The guinea pig model of recurrent genital herpes simplex virus type 2 (HSV-2) infection was used to test the immunotherapeutic activity of a glycoprotein subunit vaccine. Vaccine formulation consisted of three recombinant herpes simplex virus (HSV) glycoproteins, namely gB1s, gD2t and gE1t, plus aluminium hydroxide [Al(OH)3)] adjuvant. One month after viral challenge, infected animals were therapeutically immunised by seven subcutaneous injections of a low dose of antigens with a weekly interval for the first five and a fortnightly interval for the last two administrations. Results showed that the treatment was highly effective in ameliorating the recidivist pathology of animals, suggesting that this kind of vaccine formulation and administration may be helpful for therapeutic intervention in humans affected by recurrent herpes infections.     

Construction and properties of a herpes simplex virus 2 dl5-29 vaccine candidate strain encoding an HSV-1 virion host shutoff protein

The replication-defective herpes simplex virus 2 (HSV-2) dl5-29 mutant virus strain with deletions in the U_L5 and U_L29 genes has been shown to protect mice and guinea pigs against challenge with wild-type (wt) HSV-2 and to protect against ocular disease caused by HSV-1 infection. The dl5-29 strain is currently being prepared for clinical trials as a herpes vaccine candidate. As a possible approach to improve the efficacy of dl5-29 as a genital herpes vaccine, we replaced the U_L41 gene encoding the virion host shutoff function (vhs) with the U_L41 gene from HSV-1. While the HSV-2 U_L41 and HSV-1 U_L41 gene products have analogous functions, vhs-1 is 40-fold less active than vhs-2. Previously, it was shown that disruption of the U_L41 gene can increase the efficacy of dl5-29 as a vaccine against HSV-2. These properties led us to hypothesize that replacement of vhs-2 by vhs-1 would decrease cytopathic effects in infected host cells, allowing longer survival of antigen-presenting cells and induction of stronger immune responses. The new recombinant dl5-29-41.1 virus shows nearly the same immunogenicity and protection against HSV-2 challenge as the parental dl5-29 virus or a triply deleted mutant virus, dl5-29-41, in the murine model of infection, and grows to higher titers than the parental strain in complementing cells, which is important for GMP production. The results have implications for the design of future HSV-2 vaccine candidates and mechanisms of induction of protective immunity against genital herpes.     

Analysis of herpes simplex virus 1 and 2 infection in women with high risk sexual behaviour in Mexico.

BACKGROUND: This paper describes the seroprevalence and risk factors of Herpes simplex virus (HSV) infection in a group of female prostitutes from Mexico City. METHODS: Women who consented to participate in the study voluntarily attended a sexually transmitted disease (STD) clinic during 1992. A standardized questionnaire was administered and a blood sample was obtained from each participant. Type-specific Western blot serology was performed to determine the serostatus of HSV-1 and HSV-2 for participants. Bivariate and multivariate analyses were applied to identify variables associated with an increased risk for HSV infection. RESULTS: Prevalences of infection among the 997 prostitutes studied were 93.9% for HSV-1 and 60.8% for HSV-2. Only 1.8% of the women were seronegative for both viruses. The only variable associated with HSV-1 seropositivity was crowding index. The following variables were associated with an increased risk for infection with HSV-2: age, level of education, working site, born outside Mexico City and increasing time as a prostitute. CONCLUSIONS: This is the first assessment of HSV infection in Mexico and may be useful for the development and application of control and preventive measures among the prostitute population at risk of acquiring and transmitting human immunodeficiency virus (HIV) and other STD.