Department of Biomedical Science, School of Allied Health Sciences, University of Cape Coast, Cape Coast, Ghana.
Department of Molecular Medicine, School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
BMC Infect Dis. 2021 Apr 8;21(1):332. doi: 10.1186/s12879-021-06027-5.
Malaria and helminths diseases are co-endemic in most parts of sub-Saharan Africa. Immune responses from each of these pathogens interact, and these interactions may have implications on vaccines. The GMZ2 malaria vaccine candidate is a fusion protein of Plasmodium falciparum merozoite surface protein 3 (MSP3) and glutamate rich protein (GLURP R0). GMZ2 has recently showed modest efficacy in a phase IIb multicenter trial. Here, we assessed the effect of hookworm (Necator americanus) infection and anthelmintic treatment on naturally acquired antibody responses against GMZ2 and constituent antigens.
This longitudinal cross-sectional study was conducted in the Kintampo North Municipality of Ghana. Blood and stool samples were taken from 158 individuals (4-88 years old) infected with either P. falciparum alone (n = 59) or both hookworm and P. falciparum (n = 63) and uninfected endemic controls (n = 36). Stool hookworm infection was detected by the Kato-Katz method and PCR. Malaria parasitaemia was detected by RDT, light microscopy and P. falciparum-specific 18S rRNA gene PCR. Serum samples were obtained prior to hookworm treatment with a single dose of albendazole (400 mg) and 3 weeks (21 days) after treatment. Levels of IgG1, IgG3 and IgM against GMZ2, MSP3 and GLURP R0 were measured by ELISA and compared among the groups, before and after treatment.
Participants with P. falciparum and hookworm co-infection had significantly higher IgG3 levels to GMZ2 than those with only P. falciparum infection and negative control (p < 0.05) at baseline. Treatment with albendazole led to a significant reduction in IgG3 levels against both GMZ2 and GLURP R0. Similarly, IgM and IgG1 levels against MSP3 also decreased following deworming treatment.
Individuals with co-infection had higher antibody responses to GMZ2 antigen. Treatment of hookworm/malaria co-infection resulted in a reduction in antibody responses against GMZ2 and constituent antigens after albendazole treatment. Thus, hookworm infection and treatment could have a potential implication on malaria vaccine efficacy.
在撒哈拉以南非洲的大部分地区，疟疾和寄生虫疾病同时流行。来自这些病原体的免疫反应相互作用，这些相互作用可能对疫苗产生影响。GMZ2 疟疾疫苗候选物是恶性疟原虫裂殖子表面蛋白 3（MSP3）和谷氨酸丰富蛋白（GLURP R0）的融合蛋白。GMZ2 最近在一项 IIb 期多中心试验中显示出适度的疗效。在这里，我们评估了钩虫（Necator americanus）感染和驱虫治疗对自然获得的针对 GMZ2 和组成抗原的抗体反应的影响。
这项纵向横断面研究在加纳的金坦博北市进行。从感染恶性疟原虫（n=59）或钩虫和恶性疟原虫（n=63）的 158 人（4-88 岁）中采集血液和粪便样本，并采集未感染的地方对照者（n=36）。粪便钩虫感染采用加藤厚涂片法和 PCR 检测。疟原虫寄生虫血症通过 RDT、光镜和恶性疟原虫特异性 18S rRNA 基因 PCR 检测。在单次服用阿苯达唑（400mg）和治疗后 3 周（21 天）之前，从钩虫治疗前获得血清样本。通过 ELISA 测量针对 GMZ2、MSP3 和 GLURP R0 的 IgG1、IgG3 和 IgM 水平，并在治疗前后对各组进行比较。
与仅感染恶性疟原虫和阴性对照者相比，感染恶性疟原虫和钩虫的参与者在基线时对 GMZ2 的 IgG3 水平明显更高（p<0.05）。阿苯达唑治疗导致针对 GMZ2 和 GLURP R0 的 IgG3 水平显著降低。同样，驱虫治疗后 MSP3 的 IgM 和 IgG1 水平也下降。
合并感染的个体对 GMZ2 抗原的抗体反应更高。钩虫/疟疾合并感染的治疗导致阿苯达唑治疗后针对 GMZ2 和组成抗原的抗体反应减少。因此，钩虫感染和治疗可能对疟疾疫苗的疗效产生潜在影响。
