Chimeric adenoviruses for an improved HIV vaccine

用于改进艾滋病毒疫苗的嵌合腺病毒

• 批准号: 8617207
• 负责人: Qiana L Matthews
• 金额: $ 36.63万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-08 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8617207
• 关键词: Acquired Immunodeficiency Syndrome; Address; Adenovirus Vector; Adenovirus hexon capsid protein; Adenoviruses; Agreement; Animal Model; Antibodies; Antibody Formation; Antigens; Avidity; B-Lymphocytes; Biological Models; CD4 Positive T Lymphocytes; Capsid; Capsid Proteins; Cavia; Cell Maturation; Cell physiology; Cells; Cessation of life; Clinical; Complementarity Determining Regions; Data; Development; Engineering; Epitopes; Future; Generations; Genes; Genetic Transduction; Goals; HIV; HIV Antibodies; HIV Infections; HIV vaccine; HIV-1; Helper-Inducer T-Lymphocyte; Human; Humoral Immunities; Immune response; Immunity; Immunoglobulin Class Switching; In Vitro; Individual; Infection; Kinetics; Lead; Life; Malaria; Modeling; Modification; Mutation; Predisposition; Process; Property; Proteins; Pseudomonas; Rodent Model; Role; Serotyping; Serum; Severe Acute Respiratory Syndrome; Signal Transduction; Solutions; Structure of germinal center of lymph node; System; TNFRSF5 gene; Testing; Transgenes; Translations; Vaccination; Vaccine Clinical Trial; Vaccines; Viral Vector; Virus; World Health; antigen processing; base; immunogenicity; improved; in vivo; neutralizing antibody; next generation; novel; pandemic disease; pre-clinical; public health relevance; response; transduction efficiency; vaccine development; vector

DESCRIPTION (provided by applicant): Our proposal will address the need for a safe and effective HIV vaccine using next generation adenovirus (Ad) - based vectors. A variety of viral vectors have been employed to accomplish gene-based vaccination. One particularly promising approach is based upon genetic transduction via replication-incompetent adenoviral vectors (Ad). This utility has predicated the application of Ad-based vectors for a wide range of vaccine approaches, including recent studies demonstrating utility for Malaria, Ebola, SARS, Pseudomonas, and HIV. However, the recent findings of the STEP HIV vaccine clinical trial failed to reproduce promising findings seen in animal model systems. In this regard, this trial, which used a Ad5-based vaccine, failed to protect Ad5-seronegative individuals against infection and may even have enhanced infection in vaccinees with prior immunity to adenoviruses. In the aggregate, the general agreement is that efforts to reduce vector immunogenicity with respect to pre-existing Ad5 immunity will be required to generate a safer and effective Ad- based vector as an HIV vaccine. Therefore, our proposal will address these key points by engineering multiple genetic alterations as follows: (1) To evade humoral responses to the Ad5 vector, the major capsid protein hexon will be exchanged for the hexon of Ad3, a less prevalent serotype. Human immune responses largely focus on epitopes present in the hypervariable regions (HVR) of the Ad capsid hexon; therefore, a chimeric Ad5H3 capsid will evade recognition by preimmune Abs to Ad5 hexon (2) To induce HIV specific immune responses we will employ HIV capsid incorporation of antigen. We hypothesize that these Ad vectors can circumvent Ad5 immunity and provide HIV-specific immunity. The full merit of the promising adenovirus-based approach for vaccination is currently limited by host related immunity toward the vector. Accomplishing the goals of this proposal will expand our current understanding of host-vector interactions that will be critical for advancing the Ad vector platform as a viable approach for developing effective HIV vaccines. .

描述（由申请人提供）：我们的提案将解决使用下一代腺病毒（Ad）载体的安全有效的HIV疫苗的需求。多种病毒载体已被用于完成基于基因的疫苗接种。一种特别有前途的方法是通过复制无能腺病毒载体（Ad）进行遗传转导。这一实用性预示了基于广告的载体在广泛的疫苗方法中的应用，包括最近的研究证明了对疟疾、埃博拉、SARS、假单胞菌和艾滋病毒的实用性。

项目成果

Neural stem cell-derived exosomes mediate viral entry.

• DOI: 10.2147/ijn.s70999
• 发表时间: 2014
• 期刊: International journal of nanomedicine
• 影响因子: 8
• 作者: Sims B;Gu L;Krendelchtchikov A;Matthews QL
• 通讯作者: Matthews QL

Development of an Ad5H3 Chimera Using the "Antigen Capsid-Incorporation" Strategy for an Alternative Vaccination Approach.

• DOI: 10.2174/1874357901610010010
• 发表时间: 2016
• 期刊: The open virology journal
• 作者: Gu L;Icyuz M;Krendelchtchikova V;Krendelchtchikov A;Johnston AE;Matthews QL
• 通讯作者: Matthews QL

Using multivalent adenoviral vectors for HIV vaccination.

• DOI: 10.1371/journal.pone.0060347
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Gu L;Li ZC;Krendelchtchikov A;Krendelchtchikova V;Wu H;Matthews QL
• 通讯作者: Matthews QL

A recombinant adenovirus-based vector elicits a specific humoral immune response against the V3 loop of HIV-1 gp120 in mice through the "Antigen Capsid-Incorporation" strategy.

• DOI: 10.1186/1743-422x-11-112
• 发表时间: 2014-06-16
• 期刊: Virology journal
• 影响因子: 4.8
• 作者: Gu L;Krendelchtchikova V;Krendelchtchikov A;Oster RA;Fujihashi K;Matthews QL
• 通讯作者: Matthews QL