Lodmell D L, Ray N B, Parnell M J, Ewalt L C, Hanlon C A, Shaddock J H, Sanderlin D S, Rupprecht C E
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840, USA.
Nat Med. 1998 Aug;4(8):949-52. doi: 10.1038/nm0898-949.
More than 40,000 people die annually from rabies worldwide. Most of these fatalities occur in developing countries, where rabies is endemic, public health resources are inadequate and there is limited access to preventive treatment. Because of the high cost of vaccines derived from cell culture, many countries still use vaccines produced in sheep, goat or suckling mouse brain. The stability and low cost for mass production of DNA vaccines would make them ideal for use in developing countries. To investigate the potential of DNA vaccines for rabies immunization in humans, we vaccinated Macaca fascicularis (Cynomolgus) monkeys with DNA encoding the glycoprotein of the challenge virus standard rabies virus, or with a human diploid cell vaccine (HDCV). The monkeys then were challenged with a non-passaged rabies virus. DNA or HDCV vaccination elicited comparable primary and anamnestic neutralizing antibody responses. All ten vaccinated monkeys (DNA or HDCV) survived a rabies virus challenge, whereas monkeys vaccinated with only the DNA vector developed rabies. Furthermore, serum samples from DNA- or HDCV-vaccinated monkeys neutralized a global spectrum of rabies virus variants in vitro. This study shows that DNA immunization elicits protective immunity in nonhuman primates against lethal challenge with a human viral pathogen of the central nervous system. Our findings indicate that DNA vaccines may have a promising future in human rabies immunization.
全球每年有超过4万人死于狂犬病。这些死亡大多发生在发展中国家，在这些国家狂犬病呈地方性流行，公共卫生资源不足，获得预防性治疗的机会有限。由于细胞培养疫苗成本高昂，许多国家仍在使用羊、山羊或乳鼠脑制备的疫苗。DNA疫苗稳定性高且大规模生产成本低，使其成为发展中国家理想的疫苗选择。为了研究DNA疫苗用于人类狂犬病免疫的潜力，我们用编码标准狂犬病病毒糖蛋白的DNA或人二倍体细胞疫苗（HDCV）对食蟹猴（猕猴）进行免疫。然后用未传代的狂犬病病毒攻击这些猴子。DNA或HDCV免疫引发了相似的初次和回忆性中和抗体反应。所有10只接种疫苗的猴子（DNA或HDCV）在狂犬病病毒攻击中存活下来，而仅接种DNA载体的猴子则感染了狂犬病。此外，来自接种DNA或HDCV猴子的血清样本在体外中和了全球范围内的狂犬病病毒变种。本研究表明，DNA免疫可在非人灵长类动物中引发针对中枢神经系统人类病毒病原体致死性攻击的保护性免疫。我们的研究结果表明，DNA疫苗在人类狂犬病免疫方面可能具有广阔的前景。
