Novartis Vaccines and Diagnostics, Inc., Cambridge, MA 02139, United States.
Vaccine. 2012 Nov 19;30(49):6980-90. doi: 10.1016/j.vaccine.2012.09.056. Epub 2012 Oct 3.
Human cytomegalovirus (HCMV) infects the majority of the global population and persists within the infected host for life; infection of healthy adults rarely leads to severe acute clinical symptoms. In contrast, HCMV is a leading infectious cause of congenital disease and a common cause of complications in transplant recipients. A vaccine to prevent HCMV disease in these populations is a widely recognized medical need. We review recent advances in our understanding of the candidate vaccine antigens and published clinical trial data for the four most recent HCMV vaccine candidates: a gB subunit adjuvanted with MF59, a DNA vaccine expressing gB and pp65, alphavirus replicon particles (VRPs) expressing gB and a pp65-IE1 fusion protein, and a pp65 peptide vaccine. The candidates are safe, although some adverse events were reported for an adjuvanted variant of the pp65 peptide vaccine. The gB/MF59 vaccine elicited strong humoral responses with limited durability. The gB/pp65 DNA vaccine elicited cellular immunity, and the pp65 peptide vaccine elicited modest cellular immunity, but only when formulated with an adjuvant. Only the VRP vaccine expressing gB and pp65-IE1 elicited both humoral and cellular immunity. The gB/MF59 vaccine showed a short-term 50% efficacy at preventing infection of seronegative women and significantly reduced viremia and need for antivirals in solid organ transplant recipients, and the gB/pp65 DNA vaccine showed signs of clinical benefit in hematopoietic stem cell transplant recipients. Importantly, the partial efficacy of the subunit and DNA vaccines is new evidence that both humoral and cellular immunity contribute to controlling HCMV-related disease. These data show the clinical feasibility of a recombinant HCMV vaccine. We discuss areas for potential improvements in the next generation of vaccine candidates.
人巨细胞病毒（HCMV）感染全球大多数人群，并在受感染的宿主中终身存在；健康成年人感染很少导致严重的急性临床症状。相比之下，HCMV 是导致先天性疾病的主要传染性病原体，也是移植受者并发症的常见原因。预防这些人群中 HCMV 疾病的疫苗是广泛公认的医疗需求。我们回顾了最近在候选疫苗抗原方面的理解进展，并公布了四种最新的 HCMV 疫苗候选者的临床试验数据：一种用 MF59 佐剂的 gB 亚单位、一种表达 gB 和 pp65 的 DNA 疫苗、一种表达 gB 和 pp65-IE1 融合蛋白的甲型肝炎病毒复制子颗粒（VRP）和一种 pp65 肽疫苗。这些候选者是安全的，尽管一种 pp65 肽疫苗的佐剂变体报告了一些不良事件。gB/MF59 疫苗引起了强烈的体液反应，但持久性有限。gB/pp65 DNA 疫苗引起了细胞免疫，pp65 肽疫苗引起了适度的细胞免疫，但只有在与佐剂联合使用时才会引起。只有表达 gB 和 pp65-IE1 的 VRP 疫苗引起了体液和细胞免疫。gB/MF59 疫苗在预防血清阴性妇女感染方面显示出短期 50%的疗效，并显著降低了实体器官移植受者的病毒血症和抗病毒药物的需求，gB/pp65 DNA 疫苗在造血干细胞移植受者中显示出临床获益的迹象。重要的是，亚单位和 DNA 疫苗的部分疗效是新的证据，表明体液和细胞免疫都有助于控制 HCMV 相关疾病。这些数据表明了重组 HCMV 疫苗的临床可行性。我们讨论了下一代疫苗候选者的潜在改进领域。
