Pseudovirion Formation by Live Vector HIV Vaccines

活载体 HIV 疫苗形成假病毒粒子

• 批准号: 7244076
• 负责人: PAUL W. SPEARMAN
• 金额: $ 22.28万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7244076
• 关键词: Adenovirus Vector; Antibodies; Antigen Presentation; Antigens; Attenuated; B-Lymphocytes; Binding; CD4 Positive T Lymphocytes; Canarypox Vectors; Cell Communication; Cells; Dendritic Cells; Detection; Development; Evaluation; Gagging; Genes; Glycoproteins; HIV; HIV Antigens; HIV Envelope Protein gp120; HIV vaccine; HIV-1; Human; Immune response; Immunization; Laboratories; Life; Lymphoid Tissue; Measures; Modification; Molecular Conformation; Muscle; Numbers; Particulate; Poxviridae; Process; Production; Property; Receptors, Antigen, B-Cell; Recombinants; Role; Safety; Site; Staining method; Stains; System; T-Lymphocyte; Testing; Tissues; Treatment Protocols; Vaccines; base; cell type; cytokine; defective adenoviral vector; doxorubicin/mitomycin/vinblastine protocol; enzyme linked immunospot assay; immunogenicity; insight; interest; lymph nodes; macrophage; neutralizing antibody; particle; research study; response; vector; vector vaccine

DESCRIPTION (provided by applicant): The development of a safe and effective HIV vaccine is an urgent priority. Live vector HIV vaccines represent a promising means of eliciting HIV-specific cellular and humoral immune responses. The factors that contribute to a potent HIV-specific immune response to live vector vaccines remain incompletely defined. The major hypothesis of the current proposal is that pseudovirion particle formation by live vector HIV vaccines enhances cellular and humoral immune responses through delivery of particulate antigen for antigen presentation in regional lymph nodes. Our laboratory has recently demonstrated that pseudovirion production by a canarypox vector increases cellular and humoral responses to HIV antigens by comparison with a matched vector that is deficient in particle formation. Experiments described in this proposal will determine if this property is applicable to MVA and adenovirus vectors. Experiments in Aim 1 will compare the immunogenicity of live vectors that are able to produce pseudovirions with matched vectors that lack the capacity to make pseudovirions. Of particular interest is the potential for pseudovirions expressed from live HIV vaccine vectors to present envelope glycoproteins in a native conformation and generate antibodies that will effectively bind and neutralize HIV particles. In Aim 2, the potential role of Vpu in enhancing immunogenicity of live Gag-Env vectors will be analyzed. Experiments in Aim 3 will test the hypothesis that pseudovirion-competent vectors produce antigen that more efficiently reaches regional lymphoid tissue. Together, these experiments will provide important insights into the role of pseudovirions in generating HIV-specific immune responses following live vector immunization.

描述（由申请人提供）：开发安全有效的艾滋病毒疫苗是当务之急。活载体HIV疫苗代表了引发HIV特异性细胞和体液免疫应答的有希望的手段。导致对活载体疫苗产生强有力的艾滋病毒特异性免疫应答的因素仍然没有完全确定。目前的建议的主要假设是，假病毒颗粒形成活载体HIV疫苗增强细胞和体液免疫反应，通过交付颗粒抗原呈递在区域淋巴结。我们的实验室最近已经证明，假病毒粒子生产金丝雀痘病毒载体增加细胞和体液对HIV抗原的反应相比，匹配的载体，是在颗粒形成不足。本提案中描述的实验将确定该特性是否适用于MVA和腺病毒载体。目的1中的实验将比较能够产生假病毒体的活载体与缺乏产生假病毒体的能力的匹配载体的免疫原性。特别令人感兴趣的是从活HIV疫苗载体表达的假病毒体以天然构象呈递包膜糖蛋白并产生将有效结合和中和HIV颗粒的抗体的潜力。在目的2中，将分析Vpu在增强活Gag-Env载体的免疫原性中的潜在作用。目的3中的实验将检验假病毒体感受态载体产生更有效地到达区域淋巴组织的抗原的假设。总之，这些实验将提供重要的见解假病毒粒子在产生HIV特异性免疫反应后活载体免疫的作用。

项目成果

Impairment of Gag-specific CD8(+) T-cell function in mucosal and systemic compartments of simian immunodeficiency virus mac251- and simian-human immunodeficiency virus KU2-infected macaques.

猿猴免疫缺陷病毒 mac251 和猿猴人类免疫缺陷病毒 KU2 感染的猕猴粘膜和全身区室中 Gag 特异性 CD8( ) T 细胞功能受损。

• DOI: 10.1128/jvi.75.23.11483-11495.2001
• 发表时间: 2001
• 期刊: Journal of virology
• 影响因子: 5.4
• 作者: Hel,Z;Nacsa,J;Kelsall,B;Tsai,WP;Letvin,N;Parks,RW;Tryniszewska,E;Picker,L;Lewis,MG;Edghill-Smith,Y;Moniuszko,M;Pal,R;Stevceva,L;Altman,JD;Allen,TM;Watkins,D;Torres,JV;Berzofsky,JA;Belyakov,IM;Strober,W;Franc
• 通讯作者: Franc