Protein microarray antibody responses to P. falciparum in a human challenge model

人类攻击模型中对恶性疟原虫的蛋白质微阵列抗体反应

• 批准号: 10092899
• 负责人: Andrea Berry
• 金额: $ 18.3万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-06 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10092899
• 关键词: Affinity; Amino Acid Sequence; Amino Acids; Antibodies; Antibody Binding Sites; Antibody Formation; Antibody Response; Antigens; Berry; Binding; Biometry; Bite; Characteristics; Clinical Research; Culicidae; Data; Development; Development Plans; Doctor of Medicine; Epidemiology; Epitopes; Evolution; Exposure to; Falciparum Malaria; Funding; Genetic Polymorphism; Genetic Variation; Goals; Grant; Human; Immune response; Immune system; Immunity; Immunoglobulin G; Immunoglobulin M; Immunologic Memory; Individual; Infection; Knowledge; Licensure; Malaria; Malaria Vaccines; Malaria prevention; Maps; Maryland; Measures; Mentors; Mentorship; Microarray Analysis; Modeling; Morbidity - disease rate; Outcome; Parasites; Participant; Pattern; Pediatrics; Peptides; Plasmodium falciparum; Positioning Attribute; Protein Microchips; Proteins; Research; Research Personnel; Scanning; Serology; System; Training; Translational Research; Universities; Vaccine Design; Vaccines; Variant; Volunteer Group; Whole Organism; Work; career development; cross reactivity; design; experience; field study; genetic makeup; improved; individual response; insight; malaria infection; medical schools; mortality; polyclonal antibody; professor; response; vaccine development; vaccine efficacy; volunteer

PROJECT SUMMARY This K23 application is submitted by Andrea A. Berry, M.D., an Assistant Professor of Pediatrics at the University of Maryland School of Medicine. Dr. Berry's long term goal is to become an independent investigator in the field of malaria translational research. Towards this goal, she proposes a mentored career development plan that provides training in microarray analysis, biostatistics, and epidemiology. An effective Plasmodium falciparum malaria vaccine will boost prospects for the control and eventual eradication of malaria. However, the field is only beginning to understand the requirements and characteristics of malaria protective immunity, which is key to vaccine development. A promising approach is serological profiling on high-throughput protein microarrays, which can elucidate antibody responses to hundreds of P. falciparum antigen variants simultaneously. The investigator's group uses protein microarrays containing diverse variants of key P. falciparum antigens so that they can study antigen variants associated with cross- reactive and cross-protective immune responses. However, a gap in knowledge is the ability to differentiate between antibody binding due to cross-reactivity and antibody binding due to accumulated exposure to malaria – on protein microarrays, both responses manifest as reactivity to multiple antigen variants. Differentiating these two patterns of antibody binding is difficult in field studies because only limited data is available on participants' previous exposure, and even for ongoing infections one cannot always know the exact genetic makeup of the parasite or the exact timing of exposure. Elucidating the characteristics of cross-reactivity and accumulated exposure is nonetheless critical to gaining a better understanding of the development of protective immunity from malaria. Controlled Human Malaria Infections, in which volunteers are exposed to malaria through the bites of infectious mosquitoes, are an opportunity to study the effect of single-clone malaria infections on the immune response. This proposed work will evaluate immune responses in malaria naïve volunteers who experience single and repeated P. falciparum infections in order to inform the interpretation of immune responses in individuals living in malaria endemic regions. Protein and peptide microarrays will be used to probe sera from initially naïve volunteers after they have recovered from P. falciparum challenge. Aim 1: Evaluate the effect of single infections on the immune response by comparing two groups of volunteers after infection with two different P. falciparum strains. Aim 2: Evaluate the effect of repeated infection on the immune response by following a group of volunteers who experience four P. falciparum infections over two years.

项目概要 此 K23 申请由 Andrea A. Berry 医学博士提交，她是儿科助理教授 马里兰大学医学院。贝瑞博士的长期目标是成为一名独立调查员 在疟疾转化研究领域。为了实现这一目标，她提出了有指导的职业发展 提供微阵列分析、生物统计学和流行病学培训的计划。 有效的恶性疟原虫疟疾疫苗将提高控制和最终疟疾的前景 消灭疟疾。然而，该领域才刚刚开始了解其要求和特征 疟疾保护性免疫力，这是疫苗开发的关键。一种有前途的方法是血清学方法 高通量蛋白质微阵列分析，可以阐明对数百种 P. 恶性疟原虫抗原同时发生变异。研究人员的小组使用的蛋白质微阵列包含 恶性疟原虫关键抗原的多种变体，以便他们可以研究与交叉相关的抗原变体 反应性和交叉保护性免疫反应。然而，知识的差距在于区分的能力 由于交叉反应导致的抗体结合与由于累积接触疟疾而导致的抗体结合之间的关系 – 在蛋白质微阵列上，两种反应均表现为对多种抗原变体的反应性。差异化 这两种抗体结合模式在现场研究中很困难，因为只有有限的数据可用于 参与者之前的暴露情况，甚至对于持续感染，人们也不能总是知道确切的基因 寄生虫的构成或暴露的确切时间。阐明交叉反应的特征和 尽管如此，积累的接触对于更好地了解技术的发展至关重要 对疟疾的保护性免疫力。 受控人类疟疾感染，志愿者通过传染性疟疾叮咬而接触疟疾 蚊子是研究单克隆疟疾感染对免疫反应影响的一个机会。 这项拟议的工作将评估未曾患过疟疾的志愿者的免疫反应，这些志愿者经历过单一和 反复感染恶性疟原虫，以便解释生活个体的免疫反应 在疟疾流行地区。蛋白质和肽微阵列将用于探测最初的原始血清 从恶性疟原虫攻击中恢复后的志愿者。 目标 1：通过比较两组志愿者来评估单一感染对免疫反应的影响 感染两种不同的恶性疟原虫菌株后。 目标 2：通过跟踪一组志愿者来评估重复感染对免疫反应的影响 两年内经历过四次恶性疟原虫感染的人。

项目成果

Vaccine-induced seroconversion in participants in the North Carolina COVID-19 community Research Partnership.

• DOI: 10.1016/j.vaccine.2022.09.021
• 发表时间: 2022-10-06
• 期刊: VACCINE
• 影响因子: 5.5
• 作者: Friedman-Klabanoff, Deanna J.;Tjaden, Ashley H.;Santacatterina, Michele;Munawar, Iqra;Sanders, John W.;Herrington, David M.;Wierzba, Thomas F.;Berry, Andrea A.
• 通讯作者: Berry, Andrea A.

Children with cerebral malaria or severe malarial anaemia lack immunity to distinct variant surface antigen subsets.

• DOI: 10.1038/s41598-018-24462-4
• 发表时间: 2018-04-19
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Travassos MA;Niangaly A;Bailey JA;Ouattara A;Coulibaly D;Lyke KE;Laurens MB;Pablo J;Jasinskas A;Nakajima R;Berry AA;Adams M;Jacob CG;Pike A;Takala-Harrison S;Liang L;Kouriba B;Kone AK;Rowe JA;Moulds J;Diallo DA;Doumbo OK;Thera MA;Felgner PL;Plowe CV
• 通讯作者: Plowe CV

STRIDE: a command-line HMM-based identifier and sub-classifier of Plasmodium falciparum RIFIN and STEVOR variant surface antigen families.

• DOI: 10.1186/s12859-021-04515-8
• 发表时间: 2022-01-06
• 期刊: BMC bioinformatics
• 影响因子: 3
• 作者: Zhou AE;Shah ZV;Bradwell KR;Munro JB;Berry AA;Serre D;Takala-Harrison S;O'Connor TD;Silva JC;Travassos MA
• 通讯作者: Travassos MA