Measurement of Antibody Epitope Signatures by Peptide Microarrays to Determine Recency of HIV Infection

通过肽微阵列测量抗体表位特征来确定 HIV 感染的新近程度

• 批准号: 9065192
• 负责人: Timothy Jensen Henrich
• 金额: $ 22.51万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-24 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9065192
• 关键词: AIDS prevention; Algorithms; Allergic Disease; Antibodies; Antibody Diversity; Antibody Response; Avidity; Award; Binding; Binding Sites; Biological Assay; Biological Markers; CD4 Positive T Lymphocytes; Cell Count; Chronic; Communicable Diseases; Complement; Complex; Cross-Sectional Studies; Data; Development; Diagnostic; Dideoxy Chain Termination DNA Sequencing; Epidemic; Epidemiology; Epitope Mapping; Epitopes; Evaluation; Evolution; Foundations; Genome; Goals; HIV; HIV Infections; HIV-1; Immune System Diseases; Immunology; Immunology procedure; Incidence; Individual; Infection; Knowledge; Laboratories; Lead; Longitudinal Studies; Measurement; Measures; Methods; Mission; Modeling; Monitor; Outcome; Peptide Library; Peptides; Performance; Persons; Plasma; Population; Prevention program; Public Health; Qualifying; RNA; Research; Research Project Grants; Resources; Sampling; Serological; Serum; Specificity; Specimen; Staging; Testing; Time; Variant; Viral; Viremia; Work; base; design; expectation; high risk; improved; innovation; novel; prevent; public health intervention; public health relevance; research study; specific biomarkers; tool; transmission process; vaccine trial; virology

 DESCRIPTION (provided by applicant): There is a critical need in HIV research to develop a rapid, inexpensive, and accurate assay that can be used to estimate HIV incidence anywhere in the world and on any sample. In the absence of such a test, it is challenging to identify high risk populations, model transmission, and monitor the outcome of public health interventions. Our long term goal is to develop new methods to measure HIV incidence to improve HIV epidemiology in resource-poor settings. The overall objective of the proposed research is to use a cutting-edge immunologic assay, the global HIV-1 peptide microarray, to define the key epitope signatures of HIV-specific antibodies associated with different stages of HIV infection. Our central hypothesis is that the greater the duration of HIV infection, the greater the diversity of HIV-specific antibodies. The rationale for the proposed research is that, once it is known that antibody epitope signatures are associated with different stages of HIV infection, then the global HIV-1 peptide microarray can be further developed as a tool to measure HIV incidence. Guided by strong preliminary data, this hypothesis will be tested by pursuing two specific aims: 1) to identify the key epitope signatures of HIV-specific antibodies that are associated with three different stages of HIV infection (recent, chronic viremia, and ART suppression); and 2) to determine how HIV serologic diversity is associated with increasing HIV viral diversity in viremic subjects over time. Under the first aim, we will perform antibody epitope mapping with a global HIV-1 peptide microarray on individuals with known time since infection. We will complement the peptide microarray with established incidence assays to measure antibody magnitude and avidity. When the proposed studies have been completed, it is our expectation that the breadth of antibody epitope signatures will be significantly increased in non-recent HIV stages compared to in recent HIV infection. Under the second aim, we will determine the relationship between diversity of HIV epitope- specific antibody responses (as measured by peptide microarray) and HIV viral diversity (as measured by single genome amplification and Sanger sequencing) to provide a better pathogenic understanding of antibody evolution and how it relates to HIV incidence. When these studies have been completed, it is our expectation that the depth of antibody binding (# sequence variants recognized at any given binding site) will be positively associated with increasing HIV viral diversity measures over time. The research proposed in this application is innovative, in our opinion, because it introduces a novel high-throughput antibody-based assay that has the potential to be as sensitive and specific for recent HIV infection as a viral diversity assay. The proposed research is significant, because it is expected to be the demonstration that antibody epitope specificity - as measured by the diversity of antibody binding to HIV peptides - can serve as a biomarker of different stages of HIV infection. Ultimately, such knowledge will inform the design of novel HIV incidence assays that will have broad importance in the fields of HIV epidemiology and diagnostics.