Zhu Y d, Rota P, Wyatt L, Tamin A, Rozenblatt S, Lerche N, Moss B, Bellini W, McChesney M
The California Regional Primate Research Center, University of California, Davis, California, 95616, USA.
Virology. 2000 Oct 10;276(1):202-13. doi: 10.1006/viro.2000.0564.
Immunization of newborn infants with standard measles vaccines is not effective because of the presence of maternal antibody. In this study, newborn rhesus macaques were immunized with recombinant vaccinia viruses expressing measles virus hemagglutinin (H) and fusion (F) proteins, using the replication-competent WR strain of vaccinia virus or the replication-defective MVA strain. The infants were boosted at 2 months and then challenged intranasally with measles virus at 5 months of age. Some of the newborn monkeys received measles immune globulin (MIG) prior to the first immunization, and these infants were compared to additional infants that had maternal measles-neutralizing antibody. In the absence of measles antibody, vaccination with either vector induced neutralizing antibody, cytotoxic T cell (CTL) responses to measles virus and protection from systemic measles infection and skin rash. The infants vaccinated with the MVA vector developed lower measles-neutralizing antibody titers than those vaccinated with the WR vector, and they sustained a transient measles viremia upon challenge. Either maternal antibody or passively transferred MIG blocked the humoral response to vaccination with both WR and MVA, and the frequency of positive CTL responses was reduced. Despite this inhibition of vaccine-induced immunity, there was a reduction in peak viral loads and skin rash after measles virus challenge in many of the infants with preexisting measles antibody. Therefore, vaccination using recombinant vectors such as poxviruses may be able to prevent the severe disease that often accompanies measles in infants.
由于母体抗体的存在,用标准麻疹疫苗对新生儿进行免疫接种是无效的。在本研究中,使用具有复制能力的痘苗病毒WR株或复制缺陷型MVA株,用表达麻疹病毒血凝素(H)和融合蛋白(F)的重组痘苗病毒对新生恒河猴进行免疫接种。这些幼猴在2个月时进行加强免疫,然后在5个月大时经鼻用麻疹病毒进行攻击。一些新生猴子在首次免疫前接受了麻疹免疫球蛋白(MIG),并将这些幼猴与具有母体麻疹中和抗体的其他幼猴进行比较。在没有麻疹抗体的情况下,用任何一种载体进行疫苗接种均可诱导中和抗体、对麻疹病毒的细胞毒性T细胞(CTL)反应,并预防全身性麻疹感染和皮疹。接种MVA载体的幼猴产生的麻疹中和抗体滴度低于接种WR载体的幼猴,并且在攻击后它们出现短暂的麻疹病毒血症。母体抗体或被动转移的MIG均阻断了对WR和MVA疫苗接种的体液反应,并且阳性CTL反应的频率降低。尽管疫苗诱导的免疫受到这种抑制,但在许多预先存在麻疹抗体的婴儿中,麻疹病毒攻击后的病毒载量峰值和皮疹有所减少。因此,使用重组载体如痘病毒进行疫苗接种可能能够预防婴儿中经常伴随麻疹出现的严重疾病。