Payette Paul J, Ma Xiaoying, Weeratna Risini D, McCluskie Michael J, Shapiro Max, Engle Ron E, Davis Heather L, Purcell Robert H
Coley Pharmaceutical Canada, Ottawa, Canada.
Intervirology. 2006;49(3):144-51. doi: 10.1159/000089375.
Despite the existence for some time of effective prophylactic vaccines, hepatitis B virus (HBV) infection remains an important global concern. Improvements on existing vaccines could be beneficial, especially in situations where it is desirable or necessary to induce protective immunity more rapidly or with fewer doses. We have compared, in chimpanzees, a current HBV vaccine that contains recombinant hepatitis B surface antigen HBsAg) adsorbed to alum, with two novel vaccine strategies that have proven superior to the current vaccine in mice. The first approach was the use of oligodeoxynucleotides containing CpG motifs (CpG ODN) as an adjuvant to Engerix-B, a commercial HBV vaccine. The addition of CpG ODN to Engerix-B greatly improved the kinetics and magnitude of the humoral response, suggesting that CpG ODN might allow induction of protective immunity in humans more quickly and with fewer vaccine doses. All animals receiving either control or CpG-containing subunit vaccines at 0 and 4 weeks attained titers of HBsAg-specific antibody (anti-HBs) considered protective (> or =10 mIU/ml) and were indeed protected from challenge at 8 weeks with 10(3.5) 50% chimp infectious doses (CID(50)) of intravenous HBV. The second approach was a DNA vaccine with a plasmid vector optimized for content of immunostimulatory CpG motifs. Despite the fact that earlier studies had shown four doses of a similar DNA vaccine (except not optimized for CpG content) to induce strong humoral responses in 1 of 2 chimpanzees, in this study two doses of DNA vaccine (at 0 and 4 weeks) did not generate any detectable anti-HBs in either of 2 chimpanzees, although it did protect 1 that rapidly developed anti-HBs during the incubation period, suggesting priming of an antibody response. The poor results may be due to an inadequate number of doses or amount of plasmid DNA in these larger animals, but nevertheless point to the need to improve delivery methods for DNA vaccines for use in larger animals such as primates.
尽管有效的预防性疫苗已经存在了一段时间，但乙型肝炎病毒（HBV）感染仍然是一个重要的全球问题。改进现有疫苗可能会有益处，特别是在希望或需要更快速地诱导保护性免疫或减少剂量的情况下。我们在黑猩猩中比较了一种目前的HBV疫苗（其含有吸附在明矾上的重组乙型肝炎表面抗原[HBsAg]）与两种新的疫苗策略，这两种新策略在小鼠中已被证明优于目前的疫苗。第一种方法是使用含有CpG基序的寡脱氧核苷酸（CpG ODN）作为商业HBV疫苗Engerix - B的佐剂。将CpG ODN添加到Engerix - B中极大地改善了体液反应的动力学和强度，这表明CpG ODN可能使人类能够更快且用更少的疫苗剂量诱导保护性免疫。所有在0周和4周接受对照或含CpG亚单位疫苗的动物都获得了被认为具有保护性的HBsAg特异性抗体（抗 - HBs）滴度（≥10 mIU/ml），并且在8周时确实受到了10(3.5) 50%黑猩猩感染剂量（CID(50)）静脉注射HBV攻击的保护。第二种方法是一种DNA疫苗，其质粒载体针对免疫刺激CpG基序的含量进行了优化。尽管早期研究表明四剂类似的DNA疫苗（除了未针对CpG含量进行优化）能在2只黑猩猩中的1只诱导强烈的体液反应，但在本研究中，两剂DNA疫苗（在0周和4周）在2只黑猩猩中均未产生任何可检测到的抗 - HBs，尽管它确实保护了1只在潜伏期迅速产生抗 - HBs的黑猩猩，提示引发了抗体反应。结果不佳可能是由于这些较大动物中剂量数量不足或质粒DNA量不足，但尽管如此，这也表明需要改进用于灵长类等较大动物的DNA疫苗的递送方法。
