Arévalo-Herrera Myriam, Lopez-Perez Mary, Dotsey Emmanuel, Jain Aarti, Rubiano Kelly, Felgner Philip L, Davies D Huw, Herrera Sócrates
Malaria Vaccine and Drug Development Center (MVDC), Cali, Colombia.
Faculty of Health, Universidad del Valle, Cali, Colombia.
PLoS Negl Trop Dis. 2016 Mar 25;10(3):e0004563. doi: 10.1371/journal.pntd.0004563. eCollection 2016 Mar.
Acquisition of malaria immunity in low transmission areas usually occurs after relatively few exposures to the parasite. A recent Plasmodium vivax experimental challenge trial in malaria naïve and semi-immune volunteers from Colombia showed that all naïve individuals developed malaria symptoms, whereas semi-immune subjects were asymptomatic or displayed attenuated symptoms. Sera from these individuals were analyzed by protein microarray to identify antibodies associated with clinical protection.
METHODOLOGY/PRINCIPAL FINDINGS: Serum samples from naïve (n = 7) and semi-immune (n = 9) volunteers exposed to P. vivax sporozoite-infected mosquito bites were probed against a custom protein microarray displaying 515 P. vivax antigens. The array revealed higher serological responses in semi-immune individuals before the challenge, although malaria naïve individuals also had pre-existing antibodies, which were higher in Colombians than US adults (control group). In both experimental groups the response to the P. vivax challenge peaked at day 45 and returned to near baseline at day 145. Additional analysis indicated that semi-immune volunteers without fever displayed a lower response to the challenge, but recognized new antigens afterwards.
Clinical protection against experimental challenge in volunteers with previous P. vivax exposure was associated with elevated pre-existing antibodies, an attenuated serological response to the challenge and reactivity to new antigens.
在低传播地区,疟疾免疫力通常在相对较少接触疟原虫后获得。最近在来自哥伦比亚的未感染疟疾和具有半免疫力的志愿者身上进行的间日疟原虫实验性攻击试验表明,所有未感染个体都出现了疟疾症状,而具有半免疫力的受试者则无症状或症状较轻。通过蛋白质微阵列分析这些个体的血清,以鉴定与临床保护相关的抗体。
方法/主要发现:将来自未感染(n = 7)和具有半免疫力(n = 9)的志愿者的血清样本,这些志愿者暴露于感染间日疟原虫子孢子的蚊虫叮咬,用展示515种间日疟原虫抗原的定制蛋白质微阵列进行检测。该阵列显示,在攻击前,具有半免疫力的个体血清学反应更高,尽管未感染疟疾的个体也有预先存在的抗体,哥伦比亚人的这些抗体高于美国成年人(对照组)。在两个实验组中,对间日疟原虫攻击的反应在第45天达到峰值,并在第145天恢复到接近基线水平。进一步分析表明,无发热的具有半免疫力的志愿者对攻击的反应较低,但之后识别出新的抗原。
对先前接触过间日疟原虫的志愿者进行实验性攻击的临床保护与预先存在的抗体升高、对攻击的血清学反应减弱以及对新抗原的反应性有关。