单克隆抗体治疗家兔实验性单纯疱疹性角膜炎

单纯疱疹性角膜炎(HSK)是感染性角膜炎中最主要的致盲性眼病,多由单纯疱疾病毒Ⅰ型(HSV-1)引起,常用疱疹净、无环鸟苷等抗代谢药物作局部治疗,但疗效不够显著,并有细胞毒性等副作用。本文选用抗HSV糖蛋白gC单克隆抗体(McAb)2C5、2A8、1A12、Mad-2和抗gD McAb1D10的腹水,纯化后制成滴眼剂。取灰色家兔21只42眼,用HSV-1感染造成实验性HSK。治疗1组和治疗2组各为12只眼,     

单克隆抗体治疗家兔实验性单纯疱疹性角膜炎

单纯疱疹性角膜炎(HSK)是感染性角膜炎中最主要的致盲性眼病,病程迁延,患者痛苦。该病多由单纯疱疹病毒1型(HSV-1)引起,药物局部治疗是目前治疗该病的主要方法。常用药物有疱疹净、无环鸟苷等抗代谢药,但疗效不够显著,并有细胞毒性等副作用。本文将抗HSV糖蛋白单克隆抗体(McAb)应用于家兔实验性单纯疱疹性角膜炎的治疗,现将初步结果报告如下。     

单克隆抗体治疗单纯疱疹性角膜炎的临床观察

单纯疱疹性角膜炎(HSK)是主要的致盲性眼病之，多由于单纯疱疹病毒1型(HSV-1)感染所致。现应用一些抗代谢药物如疱疹净、无环鸟昔等治疗，虽有一定作用，但疗效不够显著，且对正常细胞也有毒性作用。因此，寻找一种即能抑制病毒增殖，对正常细胞毒性又小的药物，是临床上急待解决的问题。本文应用本校分子病毒学研究室制备的抗HSV糖蛋白单克隆抗体(McAb)治疗HSK，取得较为满意的效果，初报如下。     

单克隆抗体治疗家兔实验性单纯疱疹性角膜炎

单纯疱疹性角膜炎(HSK)是感染性角膜炎中最主要的致盲性眼病，病程迁延，患者痛苦。该病多由单纯疱疹病毒1型(HSV-1)引起，药物局部治疗是目前治疗该病的主要方法。常用药物有疱疹净，无环鸟苷等抗代谢药，但疗效不够显著，并有细胞毒性等副作用。本文将抗HSV糖蛋白单克隆抗体(MeAb)应用于家兔实验性单纯疱疹性角膜炎的治疗，现将初步结果报告如下。     

单克隆抗体治疗单纯疱疹性角膜炎的临床观察

单纯疱疹病毒(HSV)所致单纯疱疹性角膜炎(HSK)是目前眼科常见和严重的角膜病。由于HSK具有反复发作和迁延不愈的特点,所以对于许多反复发作和抗病毒药物治疗无效的病人,临床上尚无有效的治疗方法。本文应用抗HSV糖蛋白gC和gD的单克隆抗体(McAb)治疗HSK,取得较为满意的结果。 自1987年12月至1989年5月,共治疗HSK43例46只眼,其中右眼22只,左眼24只;男31例,女12例;年龄5～63岁;初发25例,复发18例;病程一般1～3个月,最     

单克隆抗体治疗单纯疱疹性角膜炎的临床观察

单纯疱疹性角膜炎(HSK)是主要的致盲性眼病之一,多由于单纯疱疹病毒1型(HSV-1)感染所致。现应用一些抗代谢药物如疱疹净、无环鸟苷等治疗,虽有一定作用,但疗效不够显著,且对正常细胞也有毒性作用。因此,寻找一种即能抑制病毒增殖,对正常细胞毒性又小的药物,是临床上急待解决的问题。本文应用本校分子病毒学研究室制备的抗HSV糖蛋白单克隆抗体(McAb)治疗HSK,取得较为满意削效果,初报如下。     

单纯疱疹病毒糖蛋白C的鉴定

业已发现的单纯疱疹病毒(HSV)糖蛋白有6种即gB、gC、gD、gE,gG和gH。糖蛋白C(gC)既可诱生中和抗体,也能诱导细胞免疫,gC-1还起到补体C3b受体的作用。本文采用放射免疫沉淀试验和用HSV-1/HSV-2型间重组株作物理图谱等方法,鉴定出6株单克隆抗体(McAb)的靶抗原为gC。 6株抗HSV的MeAbs 1A12、1C4     

McAb-ELISA双夹心法分型检测单纯疱疹病毒抗原(简报)

单纯疱疹病毒(HSV)分为两型,HSV-1和HSV-2,可引起龈口炎 口唇疱疹 皮肤疱疹 疱疹性角膜炎 生殖器疱疹 疱疹性脑炎 宫颈炎等,并认为与宫颈癌的发生有关。近年来,在性传播性疾病(STD) 妇幼保健和优生优育方面,HSV的危害愈来愈受到高度重视,为了更有效控制HSV感染的流行,本文建立了一种可快速 特异检测HSV抗原的双McAb-ELISA夹心法。     

单纯疱疹病毒糖蛋白模拟位的研究

目的 为了充分认识单纯疱疹病毒（HSV）糖蛋白的抗原表位，寻找HSV多组分疫苗和新型基因工程疫苗更有效的小片段短肽作为该病毒疫苗的备选免疫原。方法 利用有动物保护活性的抗HSV糖蛋白C（gC)单克隆抗体（McAb)1A12淘筛噬菌体随机12肽库，经4轮筛选后进行ELISA检测，随机挑取14个阳性克隆进行序列测定，序列比较后得到保守序列，做ELISA阻断实验进一步鉴定筛选结果并与相关天然蛋白HSV gC进行序列比较。结果 获得保守序列－SG（L）RHII－和其侧翼辅助序列－AK－、－VW－，其与天然相关蛋白HSV gC114-116位氨基酸十分相似。携有此短肽的噬菌体可以与McAb特异结合，并可部分阻断抗体与HSV囊膜抗原的反应。结论 所筛选到的保守序列可模拟McAb针对的抗原表位，可能是HSV的替代抗原。这一研究方法有望使短肽替代庞大的糖蛋白全长氨基酸序列，为研制更有效及更广谱的基因工程疫苗提供依据，也使研制基于抗原表位水平的特异诊断试剂成为可能。     

单纯疱疹病毒1型约105000道尔顿糖蛋白的鉴定及其编码基因的定位

用放射免疫沉淀试验和用单纯疱疹病毒1型与2型(HSV-1/HSV—2)型间重组林作物理图谱的方法,鉴定出单克隆抗体(McAb)1A12目标抗原是一分子量约为105,000道尔顿的糖蛋白,存在于HSV—1感染的BHK细胞提取物中,其编码基因定位于长单一序列(UL)上,在0.640-0.682遗传单位之间。由于该糖蛋白的编码基因与gC编码基因部分重叠,因此该糖蛋白可能是gC的另一种形式。     

单纯疱疹病毒糖蛋白单克隆抗体对致死性腹腔感染BALB/c幼鼠的被动保护作用

用单纯疤疹病毒(HSV)Ⅰ型SM44株和Ⅱ型SaV株分别腹腔感染BALB/c小鼠,于感染前后不同时间经腹腔注射HSV单克隆抗体(McAb)观察6株McAbs对致死性腹腔感染小鼠的被动保护作用。结果4株McAbs(2C5、1A12、Mad-2、1D10)对HSV-Ⅰ感染的小鼠有保护作用,5株McAbs(2C5、1A12、2A8、1D10、CH-A9)对HSV-Ⅱ感染的小鼠有保护作用。体内保护作用与体外的中和活性相关;并分析了McAbs在中和试验中有无补体参与条件下的保护能力。还证实了HSV糖蛋白在急性感染病程中其型特异性和型共同性抗原决定簇在体内的表达。     

Sequential Changes in T and B Lymphocyte Responses to Herpes Simplex Virus in Man

Lymphocytes of seven patients with primary herpetic infection, twenty-three patients with recurrent herpes labialis and of nineteen control subjects were separated into T and B enriched cells by the use of nylon wool columns. In the absence of a herpetic infection the thymidine incorporation and macrophage migration inhibition responses to herpes simplex virus (HSV), Candida albicans and PPD, and the thymidine incorporation induced by PHA were functions of T cells. When a herpetic infection was present, the unfractionated lymphocyte response to HSV was increased, as measured by thymidine incorporation, but the T cell response was unchanged. However, T cells did show an increased response to HSV when prepared by elimination of cells forming rosettes with zymosan-complement. T cells of some patients were stimulated by contact with zymosan, and this correlated with the response to C. albicans. It is suggested that lymphocyte responses to HSV in man are mediated by T cells, but that these cells are specifically retained by nylon wool columns at the time of a herpetic infection. This may be associated with acquisition of an Fc receptor by the sensitized T cells.     

ELISA检测妇女生殖器疱疹中单纯疱疹病毒型特异性抗原的研究

用抗HSV型共同性McAb和抗HSV-2型特异性McAb包被微板,建立了能检测妇女生殖器疤疹的宫颈或阴道棉拭标本中HSV抗原,并可分型的ELISA。经与病毒分离和中和试验分型对照研究,证明本法快速、敏感、特异,分型准确可靠,可用于大规模现场普查。用本法分型检测了宫颈糜烂、霉菌性阴道炎、淋病和滴虫性阴道炎标本中的HSV抗原,结果提示上述疾病均可感染或并发感染HSV,其中以HSV-2感染为主,占24.51％,HSV-1感染次之,占6.94％。宫颈糜烂的程度与HSV阳性检出率呈正相关。淋病患者并发HSV感染的机会更多,其中HSV-1感染较其它疾病多见。故预防HSV性传播和产道感染给新生儿,应得到高度重视。     

Sequential Changes in Cell-Mediated Immune Responses to Herpes Simplex Virus After Recurrent Herpetic Infection in Humans

Lymphocyte responses to herpes simplex virus (HSV) were studied in 23 patients with recurrent herpes labialis and in 19 control subjects. Lymphocytes of seropositive, but not seronegative, controls responded to HSV by thymidine incorporation, and the supernatant fluids inhibited the migration of guinea pig macrophages. Lymphocytes from patients with a recurrent herpetic lesion responded to HSV by significantly greater thymidine incorporation than seropositive controls, but supernatants did not show an increased macrophage migration inhibition response. During the 28 days after the onset of a lesion, the thymidine incorporation to HSV fell to the level of the seropositive controls, and supernatants then induced an increased inhibition of macrophage migration. Lymphocyte responses to Candida albicans, purified protein derivative, or phytohemagglutinin did not fluctuate according to the presence of a lesion and did not differ from those of the controls. Lymphocyte responses to HSV were unaffected by culture in the presence of serum from seronegative or seropositive controls, or from patients with or without a herpetic lesion. It is suggested that in patients with recurrent herpes labialis a periodic defect of the migration inhibition response might have allowed the recurrent infection to develop, and that the increased thymidine incorporation stimulated by HSV in vitro is a result of antigenic stimulation from the lesion.     

Seroepidemiology of Herpes Simplex Virus and Restriction Endonuclease Cleavage Analysis of Herpes Simplex Virus Type 2 in Okinawa

A seroepidemiologic study of herpes simplex virus (HSV) in Okinawa was performed. A total of 423 serum samples were collected from all over Okinawa, and the positivity rate of antibody against HSV was measured using a passive hemagglutination method. The sero positive rate for HSV in age groups of over 40 years was 100%. Seven HSV type 2 (HSV 2) isolates were obtained in Okinawa, and DNA preparations from Vero cells infected with the isolates were analyzed using five restriction endonucleases: Bam HI, Hind III, Kpn I, Bgl II and Eco Rl. Variations in the genomic region were demonstrated in five of the isolates. Such variations have not been reported previously in HSV 2 in mainland Japan. This is the first report of a seroepidemiologic study of HSV and restriction endonuclease cleavage analysis of HSV 2 in Okinawa, is a subtropical island where HSV is endemic. Acta Pathol Jpn 41: 24–30, 1991.     

Characterization of a Type-Common Human Recombinant Monoclonal Antibody to Herpes Simplex Virus with High Therapeutic Potential

We report the characterization of a type-common human recombinant monoclonal antibody previously isolated by antigen selection from a phage-displayed combinatorial antibody library established from a herpes simplex virus (HSV)-seropositive individual. Competition with well-characterized murine monoclonal antibodies and immunodetection of gD truncations revealed that this antibody recognizes the group Ib antigenic site of glycoprotein D, a highly conserved and protective type-common determinant. To our knowledge, this is the first human group Ib monoclonal antibody ever described. The antibody also displayed first-order neutralization kinetics and a high neutralization rate constant, was capable of completely inhibiting syncytium formation by a fusogenic strain of HSV type 1, and efficiently neutralized low-passage clinical isolates of both HSV serotypes. Taken together with our earlier observations of the in vivo antiviral activities of this human recombinant antibody in animal models of HSV infection, the present results support the high therapeutic potential of this antibody.     

ELISA for the detection of herpes simplex virus antigens in the cerebrospinal fluid of patients with encephalitis

An inhibition enzyme-linked immunosorbent assay (ELISA) for the detection of herpes simplex virus antigens in cerebrospinal fluid (CSF) has been developed. A Triton X-100 extract of herpes simplex virus type 1 (HSV-1) infected HEp-2 cells was used to coat wells of polyvinyl chloride plates. Rabbit anti-HSV-1 globulin served as the reference antibody and the CSF specimens were tested at a final dilution of 1:4. Positive results were obtained in CSF specimens from 11/18 (61%) neonates with HSV infection, 15/23 (65%) older individuals with HSV culture positive brain biopsies, and in 4/29 (14%) patients with culture negative brain biopsies. The assay was negative with CSF from 14 infants without HSV infections, from 30 patients with bacterial meningitis and 10 with cryptococcal meningitis. The test was positive in 10/21 patients within 10 days of onset, 11/14 within 11-20 days, and in 5/6 more than 20 days after onset of the herpetic infection. The overall sensitivity of the assay was 63% and the specificity was 95%.     

Diagnosis of Herpes Simplex Encephalitis by ELISA Using Antipeptide Antibodies Against Type-Common Epitopes of Glycoprotein B of Herpes Simplex Viruses

Herpes simplex encephalitis (HSE) represents one of the most severe infectious diseases of the central nervous system (CNS). As effective antiviral drugs are available, an early, rapid, and reliable diagnosis has become important. The objective of this article was to develop a sensitive ELISA protocol for herpes simplex viruses (HSV) antigen detection and quantitation by assessing the usefulness of antipeptide antibodies against potential peptides of HSV glycoprotein B (gB). A total of 180 cerebrospinal fluid (CSF) samples of HSE and non-HSE patients were analyzed using a panel of antipeptide antibodies against synthetic peptides of HSV glycoprotein gB. The cases of confirmed and suspected HSE showed 80% and 51% positivity for antipeptide against synthetic peptide QLHDLRF and 77% and 53% positivity for antipeptide against synthetic peptide MKALYPLTT, respectively for the detection of HSV antigen in CSF. The concentration of HSV antigen was found to be higher in confirmed HSE as compared to suspected HSE group and the viral load correlated well with antigen concentration obtained using the two antipeptides in CSF of confirmed HSE group. This is the first article describing the use of antibodies obtained against synthetic peptides derived from HSV in diagnostics of HSE using patients’ CSF samples.     

Herpes simplex lymphadenitis

Localized herpetic lymphadenitis is an extremely uncommon complication of herpes simplex virus (HSV) infection. The authors report two cases of localized herpetic lymphadenitis, both showing well-circumscribed areas of necrosis containing cells with diagnostic intranuclear inclusions. Electron microscopic studies in both cases revealed characteristic viral particles, and in situ hybridization studies using a herpes simplex genomic probe demonstrated HSV DNA in both specimens. Immunohistochemical studies demonstrated that the cells containing the inclusions were stromal, not lymphoid, cells. Combining the current two cases with the six well-documented cases previously reported in the literature, seven of the eight cases of HSV lymphadenitis have developed in inguinal lymph nodes, with four occurring in patients with previously or subsequently diagnosed hematopoietic malignancies, including both patients in the current series.     

Acute Morphine Administration Reduces Cell-Mediated Immunity and Induces Reactivation of Latent Herpes Simplex Virus Type 1 in BALB/c Mice

Acute morphine administration is known to alter the course of herpes simplex virus infection. In this study, the effect of acute morphine administration on the reactivation of latent herpes was investigated in a mouse model. Because of the important role of cytolytic T lymphocyte （CTL） activity in the inhibition of herpes simplex virus type 1 （HSV-1） reactivation, the effect of acute morphine administration on CTL responses was also evaluated. Furthermore, lymphocyte proliferation and IFN-γ production were evaluated for their roles in the induction of the CTL response. The findings showed that acute morphine administration significantly reduced CTL responses, lymphocyte proliferation, and IFN-γ production. Furthermore, acute morphine administration has been shown to reactivate latent HSV-γ. Previous studies have shown that cellular immune responses have important roles in the inhibition of HSV reactivation. These findings suggest that suppression of a portion of the cellular immune response after acute morphine administration may constitute one part of the mechanism that induces HSV reactivation.