Bennett Jason W, Yadava Anjali, Tosh Donna, Sattabongkot Jetsumon, Komisar Jack, Ware Lisa A, McCarthy William F, Cowden Jessica J, Regules Jason, Spring Michele D, Paolino Kristopher, Hartzell Joshua D, Cummings James F, Richie Thomas L, Lumsden Joanne, Kamau Edwin, Murphy Jittawadee, Lee Cynthia, Parekh Falgunee, Birkett Ashley, Cohen Joe, Ballou W Ripley, Polhemus Mark E, Vanloubbeeck Yannick F, Vekemans Johan, Ockenhouse Christian F
Malaria Vaccine Brach, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
PLoS Negl Trop Dis. 2016 Feb 26;10(2):e0004423. doi: 10.1371/journal.pntd.0004423. eCollection 2016 Feb.
A vaccine to prevent infection and disease caused by Plasmodium vivax is needed both to reduce the morbidity caused by this parasite and as a key component in efforts to eradicate malaria worldwide. Vivax malaria protein 1 (VMP001), a novel chimeric protein that incorporates the amino- and carboxy- terminal regions of the circumsporozoite protein (CSP) and a truncated repeat region that contains repeat sequences from both the VK210 (type 1) and the VK247 (type 2) parasites, was developed as a vaccine candidate for global use.
We conducted a first-in-human Phase 1 dose escalation vaccine study with controlled human malaria infection (CHMI) of VMP001 formulated in the GSK Adjuvant System AS01B. A total of 30 volunteers divided into 3 groups (10 per group) were given 3 intramuscular injections of 15 μg, 30 μg, or 60 μg respectively of VMP001, all formulated in 500 μL of AS01B at each immunization. All vaccinated volunteers participated in a P. vivax CHMI 14 days following the third immunization. Six non-vaccinated subjects served as infectivity controls.
The vaccine was shown to be well tolerated and immunogenic. All volunteers generated robust humoral and cellular immune responses to the vaccine antigen. Vaccination did not induce sterile protection; however, a small but significant delay in time to parasitemia was seen in 59% of vaccinated subjects compared to the control group. An association was identified between levels of anti-type 1 repeat antibodies and prepatent period.
This trial was the first to assess the efficacy of a P. vivax CSP vaccine candidate by CHMI. The association of type 1 repeat-specific antibody responses with delay in the prepatency period suggests that augmenting the immune responses to this domain may improve strain-specific vaccine efficacy. The availability of a P. vivax CHMI model will accelerate the process of P. vivax vaccine development, allowing better selection of candidate vaccines for advancement to field trials.
需要一种预防间日疟原虫感染和疾病的疫苗，以降低这种寄生虫引起的发病率，并作为全球根除疟疾努力的关键组成部分。间日疟原虫疟疾蛋白1（VMP001）是一种新型嵌合蛋白，它整合了环子孢子蛋白（CSP）的氨基末端和羧基末端区域以及一个截短的重复区域，该重复区域包含来自VK210（1型）和VK247（2型）寄生虫的重复序列，被开发为一种全球通用的候选疫苗。
我们进行了一项针对人类的1期剂量递增疫苗研究，采用在葛兰素史克佐剂系统AS01B中配制的VMP001进行受控人类疟疾感染（CHMI）。总共30名志愿者分为3组（每组10人），分别接受3次肌肉注射，每次免疫时分别注射15μg、30μg或60μg的VMP001，所有疫苗均在500μL的AS01B中配制。所有接种疫苗的志愿者在第三次免疫后14天参加间日疟原虫CHMI。6名未接种疫苗的受试者作为感染性对照。
该疫苗显示出良好的耐受性和免疫原性。所有志愿者对疫苗抗原产生了强烈的体液免疫和细胞免疫反应。接种疫苗并未诱导无菌保护；然而，与对照组相比，59%的接种疫苗受试者出现了寄生虫血症时间的轻微但显著延迟。在抗1型重复抗体水平与潜伏期之间发现了关联。
该试验是首次通过CHMI评估间日疟原虫CSP候选疫苗的疗效。1型重复特异性抗体反应与潜伏期延迟之间的关联表明，增强对该结构域的免疫反应可能会提高菌株特异性疫苗的疗效。间日疟原虫CHMI模型的可用性将加速间日疟原虫疫苗的开发过程，有助于更好地选择候选疫苗推进到现场试验。
