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用2型单纯疱疹病毒糖蛋白B和C进行DNA免疫诱导的免疫

Immunity induced by DNA immunization with herpes simplex virus type 2 glycoproteins B and C.

作者信息

Mester J C, Twomey T A, Tepe E T, Bernstein D I

机构信息

Division of Infectious Diseases, Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA.

出版信息

Vaccine. 1999 Dec 10;18(9-10):875-83. doi: 10.1016/s0264-410x(99)00325-4.

Abstract

The complete sequence of herpes simplex virus type 2 (HSV-2) glycoproteins B and C (gB & gC) were cloned into plasmid expression vectors and evaluated in murine and guinea pig genital HSV-2 models. Balb/c mice were immunized with either pgB-2 or pgC-2 plasmids intramuscularly (IM) or intradermally (ID). The vaccines induced HSV-2-specific neutralizing and ELISA IgG antibody, but little or no enhancement of viral clearance from the vagina was detected following intravaginal challenge. Immunization of guinea pigs with pgB-2 or pgC-2 induced ELISA IgG antibody; however, antibody titers were approximately one log(10) unit lower than that seen in HSV-2 convalescent sera. IM immunization of guinea pigs with either plasmid also did not decrease vaginal viral shedding following vaginal challenge, but the severity of the acute disease and the subsequent number of recurrent lesion days were reduced in animals immunized with pgB-2. Lastly, IM immunization of latently infected guinea pigs with a combined gB-2 and gC-2 plasmid vaccine significantly reduced the number of subsequent HSV-2 recurrences. DNA vectors expressing gB-2 or gC-2 were both immunogenic, although the gB-2 plasmid induced higher titers of antibody and significantly reduced primary and recurrent herpetic disease in the guinea pig model. These results also suggest that immunotherapy with plasmid expression vectors may be effective against recurrent genital HSV-2 disease.

摘要

单纯疱疹病毒2型(HSV - 2)糖蛋白B和C(gB和gC)的完整序列被克隆到质粒表达载体中,并在小鼠和豚鼠生殖器HSV - 2模型中进行评估。用pgB - 2或pgC - 2质粒对Balb / c小鼠进行肌肉注射(IM)或皮内注射(ID)免疫。这些疫苗诱导了HSV - 2特异性中和抗体和ELISA IgG抗体,但在阴道内攻毒后,未检测到阴道内病毒清除有明显增强。用pgB - 2或pgC - 2对豚鼠进行免疫诱导了ELISA IgG抗体;然而,抗体滴度比HSV - 2恢复期血清中的滴度低约一个log(10)单位。用任何一种质粒对豚鼠进行IM免疫在阴道攻毒后也未减少阴道病毒脱落,但用pgB - 2免疫的动物急性疾病的严重程度和随后复发病变的天数减少。最后,用gB - 2和gC - 2联合质粒疫苗对潜伏感染的豚鼠进行IM免疫显著减少了随后HSV - 2复发的次数。表达gB - 2或gC - 2的DNA载体都具有免疫原性,尽管gB - 2质粒诱导的抗体滴度更高,并在豚鼠模型中显著减少了原发性和复发性疱疹疾病。这些结果还表明,用质粒表达载体进行免疫治疗可能对复发性生殖器HSV - 2疾病有效。

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