Integrative Omics of HepB Vaccine Response in Co-Infection with Parasites

寄生虫合并感染中 HepB 疫苗反应的综合组学

• 批准号: 10224801
• 负责人: Elias K Haddad
• 金额: $ 76.12万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-10 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10224801
• 关键词: Acquired Immunodeficiency Syndrome; Affect; Africa; African; American; Animal Model; Antibodies; Antibody Response; Antigen-Antibody Complex; Antigens; B-Lymphocytes; Bacille Calmette-Guerin vaccination; Bioinformatics; CD8-Positive T-Lymphocytes; Cells; Clinical; Communities; Computer Models; Computing Methodologies; Custom; Data; Databases; Development; Disease; Ensure; Epigenetic Process; European; Failure; Foundations; Future; Generations; Genetic Transcription; Guidelines; HIV/TB; Helminths; High Prevalence; Human; Immune; Immune Targeting; Immune response; Immunity; Immunological Models; Immunologics; Impairment; Individual; Infection; Inflammatory; Innate Immune Response; Innate Immune System; Intestines; Link; Low Prevalence; Malaria; Mammals; Medicine; Metabolic Diseases; Molecular Profiling; Mus; Natural Immunity; Parasites; Parasitic Diseases; Parasitic infection; Participant; Phenotype; Physiological; Population; Process; Reporting; Research; Schistosoma; Schistosoma mansoni; Schistosomiasis; Soil; Structure; Surveys; System; Systems Biology; T-Lymphocyte; Testing; Tuberculosis; Vaccination; Vaccines; Virus Diseases; Visualization; Work; adaptive immunity; co-infection; cohort; cytokine; digital; genome-wide; gut microbiome; helminth infection; human disease; immunological intervention; improved; innovation; microbiome; microbiome alteration; microbiome analysis; molecular modeling; novel strategies; novel vaccines; prevent; programs; public health intervention; response; vaccine access; vaccine development; vaccine efficacy; vaccine response; vaccine-induced immunity

Summary: In parts of Africa, there is a heavy burden of parasitic diseases, including intestinal worms of several genera, collectively called helminths, and malaria. Some recent studies have implicated the worms in particular, in biasing the immune response towards a Th2 phenotype resulting in alteration of T cell and B cell responses. In fact recent work in mice has shown that pre-existing infection with Schistosoma mansoni down-regulates anti-HepB antibody levels and reduces response to vaccine and multiple reports have indicated that helminthic infections may be a contributing cause for weak responsiveness to the vaccines. However, very little information is available on the influence of parasites in general or helminth in particular on host immune response to vaccines in humans. A second critical contributor to diseases and many physiological parameters in humans is the microbiome. The intestinal microbiome has been shown to be related to a broad range of human diseases including many viral and metabolic diseases. Despite this emerging recognition that the microbiome has profound effects on immune and inflammatory processes in mammals, the effects of the microbiome on vaccine responses are less well defined. Our major hypothesis is that parasitic infection will alter the HepB vaccine response by modifying the state of the innate immune system and microbiome complexity, thereby qualitatively compromising the de novo priming of vaccine-induced T cell and B cell immunity. Our objective is to integrate and develop immune models of the molecular and sub-network signatures that characterize host response to HepB vaccination from low to high helminth burden, by using innovative bioinformatics and systems biology analyses.

简介:

项目成果

Aging alters antiviral signaling pathways resulting in functional impairment in innate immunity in response to pattern recognition receptor agonists.

• DOI: 10.1007/s11357-022-00612-5
• 发表时间: 2022-10
• 期刊: GEROSCIENCE
• 影响因子: 5.6
• 作者: Connors, Jennifer;Taramangalam, Bhavani;Cusimano, Gina;Bell, Matthew R.;Matt, Stephanie M.;Runner, Kaitlyn;Gaskill, Peter J.;DeFilippis, Victor;Nikolich-Zugich, Janko;Kutzler, Michele A.;Haddad, Elias K.
• 通讯作者: Haddad, Elias K.

Lipid nanoparticles (LNP) induce activation and maturation of antigen presenting cells in young and aged individuals.

• DOI: 10.1038/s42003-023-04555-1
• 发表时间: 2023-02-17
• 期刊: Communications biology
• 影响因子: 5.9

The impact of immuno-aging on SARS-CoV-2 vaccine development.

• DOI: 10.1007/s11357-021-00323-3
• 发表时间: 2021-03
• 期刊: GeroScience
• 影响因子: 5.6
• 作者: Connors J;Bell MR;Marcy J;Kutzler M;Haddad EK
• 通讯作者: Haddad EK

Improved Durability to SARS-CoV-2 Vaccine Immunity following Coimmunization with Molecular Adjuvant Adenosine Deaminase-1.

• DOI: 10.4049/jimmunol.2200056
• 发表时间: 2022-07-01
• 期刊: Journal of immunology (Baltimore, Md. : 1950)

Germinal Center T follicular helper (GC-Tfh) cell impairment in chronic HIV infection involves c-Maf signaling.

• DOI: 10.1371/journal.ppat.1009732
• 发表时间: 2021-07
• 期刊: PLoS pathogens
• 影响因子: 6.7
• 作者: Chakhtoura M;Fang M;Cubas R;O'Connor MH;Nichols CN;Richardson B;Talla A;Moir S;Cameron MJ;Tardif V;Haddad EK
• 通讯作者: Haddad EK