Stanberry Lawrence R
The Sealy Center for Vaccine Development, The University of Texas Medical Branch, Galveston, Texas 77555-0351, USA.
Herpes. 2004 Aug;11 Suppl 3:161A-169A.
Herpes simplex virus type 2 (HSV-2) is a suitable target for a vaccine, despite available antiviral therapies, because the virus causes lifelong infection and significant medical and psychosocial morbidity. A vaccine has the potential to reduce HSV acquisition, disease severity and the number of cases of neonatal herpes. It could also reduce transmission of HIV, which is epidemiologically linked to HSV. Prophylactic vaccines for HSV-2 must give broad and durable immunity across all mucosal surfaces to be effective. This is a significant challenge, as the major determinants of effective immunity have not yet been identified. Even if full protection cannot be achieved, vaccines would still be useful if they could increase the threshold of infection, or prevent clinical disease. However, it is possible that a vaccine could reduce symptomatic disease, but not eliminate asymptomatic shedding, which could inadvertently increase transmission from individuals who believe they are not infectious. Investigated prophylactic vaccines for HSV-2, including subunit vaccines encoding HSV glycoproteins packaged with adjuvants, have shown some benefits. The Chiron gD2gB2-MF59 vaccine gave transient protection of less than 6 months. The GlaxoSmithKline gD2-alum MPL vaccine conferred a 73-74% reduction in acquisition of symptomatic HSV-2 disease and a 38-42% reduction in the acquisition of HSV-2 infection in HSV-seronegative women, but gave no protection in men or HSV-1 seropositive women. Therapeutic vaccines aim to prevent HSV recurrences or minimise disease severity and duration, thereby reducing transmission. Research indicates that to be effective, therapeutic vaccines need to stimulate strong cell-mediated immune responses. Vaccines have induced HSV-specific antibody responses alone but have failed to protect recipients from recurrences. Further research is needed to define determinants of immunity to HSV-2, including identifying HSV-2 antigens, in order to design more effective vaccines.
尽管有可用的抗病毒疗法，但2型单纯疱疹病毒（HSV-2）仍是疫苗的合适靶点，因为该病毒会导致终身感染，并引发严重的医学和心理社会疾病。疫苗有可能减少HSV的感染、疾病严重程度以及新生儿疱疹病例数。它还可以减少与HSV在流行病学上相关的HIV传播。HSV-2预防性疫苗必须在所有黏膜表面提供广泛而持久的免疫力才能有效。这是一项重大挑战，因为尚未确定有效免疫的主要决定因素。即使无法实现完全保护，如果疫苗能够提高感染阈值或预防临床疾病，仍然会很有用。然而，疫苗有可能减少症状性疾病，但无法消除无症状排毒，这可能会无意中增加那些认为自己没有传染性的个体的传播。研究过的HSV-2预防性疫苗，包括编码与佐剂包装在一起的HSV糖蛋白的亚单位疫苗，已显示出一些益处。Chiron公司的gD2gB2-MF59疫苗提供了不到6个月的短暂保护。葛兰素史克公司的gD2-明矾MPL疫苗使HSV血清阴性女性中症状性HSV-2疾病的感染率降低了73-74%，HSV-2感染的感染率降低了38-42%，但对男性或HSV-1血清阳性女性没有保护作用。治疗性疫苗旨在预防HSV复发或使疾病严重程度和持续时间最小化，从而减少传播。研究表明，治疗性疫苗要有效，需要刺激强烈的细胞介导免疫反应。疫苗单独诱导了HSV特异性抗体反应，但未能保护接受者免受复发。需要进一步研究来确定HSV-2免疫的决定因素，包括鉴定HSV-2抗原，以便设计更有效的疫苗。
