Rampling Tommy, Ewer Katie J, Bowyer Georgina, Bliss Carly M, Edwards Nick J, Wright Danny, Payne Ruth O, Venkatraman Navin, de Barra Eoghan, Snudden Claudia M, Poulton Ian D, de Graaf Hans, Sukhtankar Priya, Roberts Rachel, Ivinson Karen, Weltzin Rich, Rajkumar Bebi-Yassin, Wille-Reece Ulrike, Lee Cynthia K, Ockenhouse Christian F, Sinden Robert E, Gerry Stephen, Lawrie Alison M, Vekemans Johan, Morelle Danielle, Lievens Marc, Ballou Ripley W, Cooke Graham S, Faust Saul N, Gilbert Sarah, Hill Adrian V S
The Jenner Institute.
Royal College of Surgeons in Ireland, Dublin.
J Infect Dis. 2016 Sep 1;214(5):772-81. doi: 10.1093/infdis/jiw244. Epub 2016 Jun 15.
The need for a highly efficacious vaccine against Plasmodium falciparum remains pressing. In this controlled human malaria infection (CHMI) study, we assessed the safety, efficacy and immunogenicity of a schedule combining 2 distinct vaccine types in a staggered immunization regimen: one inducing high-titer antibodies to circumsporozoite protein (RTS,S/AS01B) and the other inducing potent T-cell responses to thrombospondin-related adhesion protein (TRAP) by using a viral vector.
Thirty-seven healthy malaria-naive adults were vaccinated with either a chimpanzee adenovirus 63 and modified vaccinia virus Ankara-vectored vaccine expressing a multiepitope string fused to TRAP and 3 doses of RTS,S/AS01B (group 1; n = 20) or 3 doses of RTS,S/AS01B alone (group 2; n = 17). CHMI was delivered by mosquito bites to 33 vaccinated subjects at week 12 after the first vaccination and to 6 unvaccinated controls.
No suspected unexpected serious adverse reactions or severe adverse events related to vaccination were reported. Protective vaccine efficacy was observed in 14 of 17 subjects (82.4%) in group 1 and 12 of 16 subjects (75%) in group 2. All control subjects received a diagnosis of blood-stage malaria parasite infection. Both vaccination regimens were immunogenic. Fourteen protected subjects underwent repeat CHMI 6 months after initial CHMI; 7 of 8 (87.5%) in group 1 and 5 of 6 (83.3%) in group 2 remained protected.
The high level of sterile efficacy observed in this trial is encouraging for further evaluation of combination approaches using these vaccine types.
NCT01883609.
对高效抗恶性疟原虫疫苗的需求仍然迫切。在这项人体疟疾感染对照（CHMI）研究中，我们评估了在交错免疫方案中联合两种不同疫苗类型的安全性、有效性和免疫原性：一种通过使用病毒载体诱导针对环子孢子蛋白的高滴度抗体（RTS,S/AS01B），另一种诱导针对血小板反应蛋白相关黏附蛋白（TRAP）的强效T细胞反应。
37名未感染过疟疾的健康成年人接种了表达与TRAP融合的多表位序列的黑猩猩腺病毒63和改良痘苗病毒安卡拉载体疫苗以及3剂RTS,S/AS01B（第1组；n = 20）或仅接种3剂RTS,S/AS01B（第2组；n = 17）。在首次接种后第12周，通过蚊虫叮咬对33名接种疫苗的受试者和6名未接种疫苗的对照者进行CHMI。
未报告与疫苗接种相关的疑似意外严重不良反应或严重不良事件。第1组17名受试者中有14名（82.4%）和第2组16名受试者中有12名（75%）观察到保护性疫苗效力。所有对照受试者均被诊断为血期疟原虫感染。两种疫苗接种方案均具有免疫原性。14名受保护的受试者在初次CHMI后6个月接受了重复CHMI；第1组8名中的7名（87.5%）和第2组6名中的5名（83.3%）仍然受到保护。
该试验中观察到的高水平无菌效力对于进一步评估使用这些疫苗类型的联合方法是令人鼓舞的。
NCT01883609。
