Polack Fernando P, Lydy Shari L, Lee Sok-Hyong, Rota Paul A, Bellini William J, Adams Robert J, Robinson Harriet L, Griffin Diane E
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Clin Vaccine Immunol. 2013 Feb;20(2):205-10. doi: 10.1128/CVI.00394-12. Epub 2012 Dec 12.
A vaccine that would protect young infants against measles could facilitate elimination efforts and decrease morbidity and mortality in developing countries. However, immaturity of the immune system is an important obstacle to the development of such a vaccine. In this study, DNA vaccines expressing the measles virus (MeV) hemagglutinin (H) protein or H and fusion (F) proteins, previously shown to protect juvenile macaques, were used to immunize groups of 4 newborn rhesus macaques. Monkeys were inoculated intradermally with 200 μg of each DNA at birth and at 10 months of age. As controls, 2 newborn macaques were similarly vaccinated with DNA encoding the influenza virus H5, and 4 received one dose of the current live attenuated MeV vaccine (LAV) intramuscularly. All monkeys were monitored for development of MeV-specific neutralizing and binding IgG antibody and cytotoxic T lymphocyte (CTL) responses. These responses were poor compared to the responses induced by LAV. At 18 months of age, all monkeys were challenged intratracheally with a wild-type strain of MeV. Monkeys that received the DNA vaccine encoding H and F, but not H alone, were primed for an MeV-specific CD8(+) CTL response but not for production of antibody. LAV-vaccinated monkeys were protected from rash and viremia, while DNA-vaccinated monkeys developed rashes, similar to control monkeys, but had 10-fold lower levels of viremia. We conclude that vaccination of infant macaques with DNA encoding MeV H and F provided only partial protection from MeV infection.
一种能够保护幼儿免受麻疹侵害的疫苗,有助于在发展中国家推动麻疹消除工作,并降低发病率和死亡率。然而,免疫系统不成熟是研发此类疫苗的一个重要障碍。在本研究中,此前已证明能保护幼年猕猴的表达麻疹病毒(MeV)血凝素(H)蛋白或H和融合(F)蛋白的DNA疫苗,被用于免疫4组新生恒河猴。这些猴子在出生时和10月龄时分别皮内接种200μg每种DNA。作为对照,2只新生猕猴同样接种编码流感病毒H5的DNA,4只则肌肉注射一剂当前的减毒活MeV疫苗(LAV)。对所有猴子监测MeV特异性中和及结合IgG抗体以及细胞毒性T淋巴细胞(CTL)反应的产生情况。与LAV诱导的反应相比,这些反应较弱。在18月龄时,所有猴子经气管内接种一株野生型MeV毒株。接种编码H和F而非仅H的DNA疫苗的猴子,对MeV特异性CD8(+) CTL反应有预激发,但对抗体产生无预激发。接种LAV的猴子免受皮疹和病毒血症影响,而接种DNA疫苗的猴子出现皮疹,与对照猴子相似,但病毒血症水平低10倍。我们得出结论,用编码MeV H和F的DNA对幼年猕猴进行疫苗接种仅提供了部分抵御MeV感染的保护。