Immunogenicity, protective efficacy, and non-replicative status of the HSV-2 vaccine candidate HSV529 in mice and guinea pigs.
Immunogenicity, protective efficacy, and non-replicative status of the HSV-2 vaccine candidate HSV529 in mice and guinea pigs.
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DOI：
10.1371/journal.pone.0121518
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Londono-Hayes P
中科院分区：
文献类型：
--
作者：
Bernard MC;Barban V;Pradezynski F;de Montfort A;Ryall R;Caillet C;Londono-Hayes P
需要HSV-2疫苗来预防生殖器疾病、潜伏感染和病毒传播。一种复制缺陷型突变病毒（dl 5 -29）在生殖器疱疹动物模型中表现出有希望的疗效。然而，尚未评价源自dl 5 -29的高度纯化的临床候选疫苗（HSV 5 - 29）的免疫原性、保护效力和非复制状态。在用HSV 529免疫的小鼠和豚鼠中测量体液和细胞免疫应答。在小鼠或未感染和HSV-1血清阳性豚鼠中测定了对阴道HSV-2感染后急性和复发性生殖器疱疹、死亡率、潜伏感染和病毒脱落的保护作用。在三种敏感的病毒复制模型中研究了HSV 529的复制和致病性：通过肌内途径接种的严重联合免疫缺陷（SCID/Beige）小鼠，通过颅内途径接种的乳鼠和阴道接种的豚鼠。HSV 529免疫诱导小鼠和豚鼠产生HSV-2中和抗体。在小鼠中，它诱导产生特异性HSV-2抗体和分泌IFNγ或IL-5的脾细胞。免疫接种通过降低死亡率、急性生殖器疾病的严重程度和频率以及病毒脱落有效地预防了所有三种动物模型中的HSV-2感染。它还减少了幼稚和HSV-1血清阳性豚鼠的神经节病毒潜伏期和复发性疾病。在SCID/Beige小鼠的肌肉、乳小鼠的脑或接种豚鼠的阴道分泌物中未检测到HSV 529复制/传播。这些结果证实了非复制状态，以及其在小鼠和豚鼠（包括HSV-1血清阳性豚鼠）中的免疫原性和有效性。在小鼠中，HSV 529产生Th 1/Th 2特征性免疫应答，这被认为是有效疫苗所必需的。这些结果进一步支持HSV 529作为预防性疫苗在人类受试者中的临床研究。
HSV-2 vaccine is needed to prevent genital disease, latent infection, and virus transmission. A replication-deficient mutant virus (dl5-29) has demonstrated promising efficacy in animal models of genital herpes. However, the immunogenicity, protective efficacy, and non-replicative status of the highly purified clinical vaccine candidate (HSV529) derived from dl5-29 have not been evaluated. Humoral and cellular immune responses were measured in mice and guinea pigs immunized with HSV529. Protection against acute and recurrent genital herpes, mortality, latent infection, and viral shedding after vaginal HSV-2 infection was determined in mice or in naïve and HSV-1 seropositive guinea pigs. HSV529 replication and pathogenicity were investigated in three sensitive models of virus replication: severe combined immunodeficient (SCID/Beige) mice inoculated by the intramuscular route, suckling mice inoculated by the intracranial route, and vaginally-inoculated guinea pigs. HSV529 immunization induced HSV-2-neutralizing antibody production in mice and guinea pigs. In mice, it induced production of specific HSV-2 antibodies and splenocytes secreting IFNγ or IL-5. Immunization effectively prevented HSV-2 infection in all three animal models by reducing mortality, acute genital disease severity and frequency, and viral shedding. It also reduced ganglionic viral latency and recurrent disease in naïve and HSV-1 seropositive guinea pigs. HSV529 replication/propagation was not detected in the muscles of SCID/Beige mice, in the brains of suckling mice, or in vaginal secretions of inoculated guinea pigs. These results confirm the non-replicative status, as well as its immunogenicity and efficacy in mice and guinea pigs, including HSV-1 seropositive guinea pigs. In mice, HSV529 produced Th1/Th2 characteristic immune response thought to be necessary for an effective vaccine. These results further support the clinical investigation of HSV529 in human subjects as a prophylactic vaccine.
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