Brown A E, Singharaj P, Webster H K, Pipithkul J, Gordon D M, Boslego J W, Krinchai K, Su-archawaratana P, Wongsrichanalai C, Ballou W R
Armed Forces Research Institute for Medical Sciences (AFRIMS), Bangkok, Thailand.
Vaccine. 1994 Feb;12(2):102-8. doi: 10.1016/0264-410x(94)90046-9.
Thai soldiers were vaccinated with a recombinant protein derived from the central repeat region of the circumsporozoite (CS) protein of Plasmodium falciparum conjugated to Toxin A (detoxified) of Pseudomonas aeruginosa (R32Tox-A) to evaluate its safety, immunogenicity and efficacy. In a randomized, double-blind manner, 199 volunteers received either R32Tox-A or a control vaccine at 0, 8 and 16 weeks. Immunization was performed in a malaria non-transmission area, after completion of which volunteers were deployed to an endemic border area and monitored closely to allow early detection and treatment of infection. The vaccine was found to be safe and to elicit antibody responses in all vaccinees. Peak CS antibody (IgG) concentrations in malaria-experienced vaccinees exceeded those in malaria-naive vaccinees (mean 40.6 versus 16.1 micrograms ml-1; p = 0.005) as well as those induced by previous CS protein-derived vaccines and observed in association with natural infections. A log-rank comparison of time to falciparum malaria revealed no differences between vaccinated and non-vaccinated subjects. Secondary analyses revealed that CS antibody levels were lower in vaccinee malaria cases than in non-cases, 3 and 5 months after the third dose of vaccine (p = 0.06 and p = 0.014, respectively). Because antibody levels had fallen substantially before peak malaria transmission occurred, the question of whether high levels of CS antibody are protective remains to be resolved.
泰国士兵接种了一种重组蛋白疫苗，该重组蛋白来源于恶性疟原虫环子孢子（CS）蛋白的中央重复区域，并与铜绿假单胞菌的毒素A（解毒型）偶联（R32Tox-A），以评估其安全性、免疫原性和有效性。199名志愿者以随机、双盲的方式在第0、8和16周分别接种了R32Tox-A或对照疫苗。免疫接种在疟疾非传播地区进行，完成后志愿者被部署到疟疾流行的边境地区，并进行密切监测，以便早期发现和治疗感染。结果发现该疫苗是安全的，并且在所有接种者中都能引发抗体反应。有疟疾感染经历的接种者中CS抗体（IgG）的峰值浓度超过了无疟疾感染经历的接种者（平均分别为40.6和16.1微克/毫升；p = 0.005），也超过了先前CS蛋白衍生疫苗诱导的浓度以及自然感染时观察到的浓度。对恶性疟发病时间的对数秩检验显示，接种疫苗和未接种疫苗的受试者之间没有差异。二次分析显示，在第三剂疫苗接种后3个月和5个月，接种疫苗的疟疾患者的CS抗体水平低于未患疟疾的患者（p分别为0.06和0.014）。由于在疟疾传播高峰期之前抗体水平已大幅下降，高水平的CS抗体是否具有保护作用的问题仍有待解决。
