Cytomegalovirus vaccines.
Cytomegalovirus vaccines.
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DOI：
10.1093/cid/cit587
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
M. McVoy
中科院分区：
文献类型：
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作者：
M. McVoy
一种有效的巨细胞病毒（CMV）疫苗可以预防大多数由先天性巨细胞病毒感染引起的出生缺陷。临床评估中的候选疫苗包括减毒活疫苗、蛋白质亚基疫苗、DNA疫苗和病毒载体疫苗。亚基方法主要关注CMV蛋白pp65和IE1作为细胞毒性T细胞的重要诱导剂和糖蛋白B （gB）作为中和抗体的重要诱导剂。由重组gB蛋白和MF59佐剂组成的疫苗将原发性感染的发生率降低了50%。最近关于巨细胞病毒进入不同细胞类型途径的揭示提示了可能的改善过程。5亚基五聚体复合体是内皮细胞和上皮细胞进入所必需的。自然感染受试者的血清含有针对该复合体的高效中和活性，而gB/MF59疫苗不能诱导类似的中和活性。疫苗诱导唾液抗体来中和上皮细胞进入的能力对于预防口腔传播尤其重要，因为第一个被感染的细胞可能是口腔黏膜的上皮细胞。此外，最近的证据表明，抗体可以抑制进入后CMV在内皮细胞和上皮细胞之间的扩散。这些活动可能限制病毒在组织中的复制或损害病毒向胎盘和胎儿的传播。因此，包含来自五聚体复合物的表位可以通过诱导有效的中和/抑制扩散的抗体来增强功效，这些抗体针对广泛细胞类型中的病毒复制。临床前开发的下一代候选疫苗包含代表部分或全部五聚体复合物的肽、亚基或多亚基复合物。方法包括多肽、重组蛋白、DNA、复制缺陷病毒载体、基因失活的巨细胞病毒和灭活的巨细胞病毒粒子。正在开发的新策略的多样性使人们乐观地认为，一个成功的候选人将出现。
An effective cytomegalovirus (CMV) vaccine could prevent the majority of birth defects caused by congenital CMV infections. Candidate vaccines in clinical evaluation include live attenuated, protein subunit, DNA, and viral-vectored approaches. Subunit approaches have focused on the CMV proteins pp65 and IE1 as important inducers of cytotoxic T cells and glycoprotein B (gB) as an important inducer of neutralizing antibodies. A vaccine comprised of recombinant gB protein with MF59 adjuvant reduced the incidence of primary infection by 50%. Recent revelations regarding CMV entry pathways into different cell types suggest a possible course for improvement. A 5-subunit pentameric complex is uniquely required for endothelial and epithelial cell entry. Sera from naturally infected subjects contain high-potency neutralizing activities specific for this complex, whereas the gB/MF59 vaccine fails to induce comparable neutralizing activities. A vaccine's ability to induce salivary antibodies that neutralize epithelial cell entry may be especially important for preventing oral transmission as the first cells infected are presumably epithelial cells of the oral mucosa. In addition, recent evidence suggests that antibodies can inhibit postentry CMV spread between endothelial and epithelial cells. Such activities may serve to limit viral replication in tissues or impair dissemination to the placenta and fetus. Thus, inclusion of epitopes derived from the pentameric complex may provide enhanced efficacy by inducing potent neutralizing/spread-inhibiting antibodies that target virus replication in a broad spectrum of cell types. Next-generation vaccine candidates in preclinical development incorporate peptides, subunits, or multisubunit complexes representing parts or all of the pentameric complex. Approaches include peptides, recombinant proteins, DNA, replication-defective viral vectors, genetically disabled CMV, and inactivated CMV virions. The diversity of novel strategies under development engenders optimism that a successful candidate will emerge.