公开(公告)号：US20160272686A1

公开(公告)日：2016-09-22

申请号：US14806742

申请日：2015-07-23

Applicant: THE CATHOLIC UNIVERSITY OF AMERICA

Inventor： Venigalla B. RAO ,  Wadad ALSALMI

IPC: C07K14/005 ,  C12N7/00

CPC classification number: C07K14/005 ,  A61K9/7023 ,  A61K39/00 ,  A61K39/12 ,  A61K39/21 ,  A61K2039/54 ,  A61K2039/627 ,  C07K1/22 ,  C07K1/36 ,  C07K14/162 ,  C07K2319/00 ,  C07K2319/20 ,  C07K2319/21 ,  C07K2319/22 ,  C07K2319/40 ,  C07K2319/50 ,  C12N7/00 ,  C12N2740/16022 ,  C12N2740/16043 ,  C12N2740/16051 ,  C12N2740/16111 ,  C12N2740/16122 ,  C12N2740/16134 ,  C12N2740/16234

Abstract: An approach of producing recombinant trimers that mimic native HIV-1 envelope trimers is developed. A recombinant protein forming the recombinant trimers encompasses a recombinant HIV-1 gp140 fused to a tag through a linker at C-terminus of the recombinant HIV-1 gp140. The linker is sufficiently long so that the tag is accessible for binding by a binding molecule bound on a solid matrix. After expressed in a cell, the recombinant protein is secreted into the culture medium and assembles into recombinant trimers therein. The recombinant trimers may be directly purified from the culture medium. Cleaved and uncleaved trimers from different clade viruses are produced.

Abstract translation: 开发了生产模仿天然HIV-1包膜三聚体的重组三聚体的方法。 形成重组三聚体的重组蛋白包含通过重组HIV-1 gp140的C-末端的接头与标签融合的重组HIV-1 gp140。 接头足够长，使得标签可通过结合在固体基质上的结合分子进行结合。 在细胞中表达后，将重组蛋白分泌到培养基中并在其中组装成重组三聚体。 重组三聚体可以从培养基中直接纯化。 产生来自不同进化枝病毒的切割和未切割的三聚体。

公开(公告)号：US20230355738A1

公开(公告)日：2023-11-09

申请号：US18138183

申请日：2023-04-24

Applicant: The Catholic University of America

Inventor： Venigalla B. RAO ,  Jingen ZHU

IPC: A61P37/04 ,  A61K39/12

CPC classification number: A61K39/12 ,  A61P37/04 ,  A61K2039/545

Abstract: A bacteriophage T4-based, multivalent/multicomponent, needle and adjuvant-free, mucosal vaccine by engineering spike trimers on capsid exterior and nucleocapsid protein in the interior is disclosed herein. Intranasal administration of this T4-COVID vaccine induces higher virus neutralization antibody titers against multiple variants, balanced Th1/Th2 antibody and cytokine responses, stronger CD4+ and CD8+ T cell immunity, and higher secretory IgA titers in sera and bronchoalveolar lavage with no effect on the gut microbiota, compared to vaccination of mice intramuscularly. The vaccine is stable at ambient temperature, induce apparent sterilizing immunity, and provide complete protection against original SARS-CoV-2 strain and its Delta variant with minimal lung histopathology. This mucosal vaccine is an excellent candidate for boosting immunity of immunized and/or as a second-generation vaccine for the unimmunized population. This needle-free platform could be used to develop effective vaccines against many other respiratory infectious pathogens including Flu and any future emerging epidemic and pandemic pathogens.

公开(公告)号：US20220033850A1

公开(公告)日：2022-02-03

申请号：US17359711

申请日：2021-06-28

Applicant: The Catholic University of America

Inventor： Venigalla B. RAO ,  Jingen ZHU

IPC: C12N15/86 ,  C12N7/00

Abstract: Described is an “artificial virus” (AV) programmed with biomolecules that can enter human cells and carry out precise human genome modification. The AVs comprise: at least one viral vector, such as bacteriophage T4; at least one therapeutic molecule, such as DNA, RNA, protein and their complex; and a lipid coating. Also described is a method of human genome modification, using such an AV, and a method of program such an AV.

公开(公告)号：US20150017198A1

公开(公告)日：2015-01-15

申请号：US14320731

申请日：2014-07-01

Applicant: The Catholic University of America

Inventor： Venigalla B. RAO ,  Pan Tao

IPC: C07K14/24

CPC classification number: C07K14/24 ,  A61K39/0291 ,  A61K2039/5256 ,  C07K14/005 ,  C07K2319/21 ,  C07K2319/40 ,  C07K2319/735 ,  C12N2795/10123 ,  Y02A50/407

Abstract: Techniques from two basic approaches, structure-based immunogen design and phage T4 nanoparticle delivery, are developed to construct new plague vaccines. The NH2-terminal β-strand of F1 of Yersinia pestis is transplanted to the COOH-terminus of F1 of Yersinia pestis and the NH2-terminus sequence flanking the β-strand of F1 of Yersinia pestis is duplicated to eliminate polymerization but to retain the T cell epitopes. The mutated F1 is fused to the V antigen of Yersinia pestis to thereby form a fusion protein F1mut-V mutant, which produces a completely soluble monomer. The fusion protein F1mut-V is then arrayed on phage T4 nanoparticles via a small outer capsid protein, Soc, from a T4 phage or a T4-related phage. Both the soluble and T4 decorated F1mut-V provided approximately 100% protection to mice and rats against pneumonic plague evoked by high doses of Yersinia pestis CO92.

Abstract translation: 开发了两种基本方法，基于结构的免疫原设计和噬菌体T4纳米颗粒递送的技术来构建新的疫苗疫苗。 将鼠疫耶尔森氏菌的F1的NH2-末端和一串被移植到鼠疫耶尔森氏菌的F1的COOH-末端，并且重复鼠疫耶尔森氏菌的F1侧链的NH2-末端序列，以消除聚合，但保留 T细胞表位。 突变的F1融合到鼠疫耶尔森氏菌的V抗原，从而形成融合蛋白F1mut-V突变体，其产生完全可溶的单体。 然后通过T4噬菌体或与T4相关的噬菌体的小外壳衣壳蛋白Soc，将融合蛋白F1mut-V排列在噬菌体T4纳米颗粒上。 可溶性和T4装饰的F1mut-V都能够对小鼠和大鼠提供大约100％的抗高剂量鼠疫耶尔森氏菌CO92诱发的肺炎瘟疫。

公开(公告)号：US20230026666A1

公开(公告)日：2023-01-26

申请号：US17736181

申请日：2022-05-04

Applicant: The Catholic University of America

Inventor： Venigalla B. RAO ,  Himanshu BATRA

IPC: C12N15/86 ,  C12N5/0783 ,  C12N7/00

Abstract: Described is an engineered viral particle programmed with T cell targeting specificity. The viral particles comprise: at least one viral vector, such as bacteriophage T4; and at least one CD4-binding protein displayed on the surface of the viral vector. Also described is a method of reactivate latent HIV-1 and cure patient with HIV-1 infection, using such an engineered viral particle.

公开(公告)号：US20220010335A1

公开(公告)日：2022-01-13

申请号：US17488542

申请日：2021-09-29

Applicant: The Catholic University of America

Inventor： Venigalla B. RAO ,  Jingen ZHU

IPC: C12N15/86

Abstract: Described is hybrid viral vector comprising: a first virus such as bacteriophage T4; one or more second virus such as adeno-associated virus (AAV) attached to the first virus through cross-bridges, such as avidin-biotin cross-bridges; one or more DNA molecules packaged in the first virus; one or more nucleic acid molecules packaged in the second virus; and one or more proteins displayed on the surface of the first virus. Also described are methods of making and using such a hybrid viral vector.

公开(公告)号：US20140329891A1

公开(公告)日：2014-11-06

申请号：US14337545

申请日：2014-07-22

Applicant: The Catholic University of America

Inventor： Venigalla B. RAO

IPC: C12N15/85

CPC classification number: C12N15/87 ,  C07K2319/10 ,  C07K2319/40 ,  C07K2319/61 ,  C12N2795/10122 ,  C12N2795/10123 ,  C12N2795/10142 ,  C12N2810/6009 ,  C12N2810/85 ,  C12N2810/859

Abstract: Described is T4 DNA packaging machine comprising: one or more DNA molecules packaged in a head of the T4 DNA packaging machine, one or more Hoc-fused proteins displayed on the head of the T4 DNA packaging machine, and one or more Soc-fused proteins displayed on the head of the T4 DNA packaging machine. Also described are methods of making and using such a T4 DNA packaging machine.

公开(公告)号：US20210054410A1

公开(公告)日：2021-02-25

申请号：US16990289

申请日：2020-08-11

Applicant: The Catholic University of America

Inventor： Venigalla B. RAO ,  Jingen ZHU

IPC: C12N15/86

Abstract: Described is hybrid viral vector comprising: a first virus such as bacteriophage T4; one or more second virus such as adeno-associated virus (AAV) attached to the first virus through cross-bridges, such as avidin-biotin cross-bridges; one or more DNA molecules packaged in the first virus; one or more nucleic acid molecules packaged in the second virus; and one or more proteins displayed on the surface of the first virus. Also described are methods of making and using such a hybrid viral vector.

公开(公告)号：US20200147207A1

公开(公告)日：2020-05-14

申请号：US16722124

申请日：2019-12-20

Applicant: The Catholic University of America

Inventor： Venigalla B. RAO

IPC: A61K39/295 ,  A61K39/02 ,  C07K19/00 ,  A61K39/07 ,  A61K39/385 ,  C07K14/005 ,  C07K14/32 ,  C07K14/24

Abstract: Bivalent immunogenic compositions against anthrax and plague are disclosed herein. One bivalent immunogenic composition comprises a triple fusion protein containing three antigens, F1 and V from Yersinia pestis and PA antigen from Bacillus anthracis fused in-frame and retaining structural and functional integrity of all three antigens. Another bivalent immunogenic composition comprises bacteriophage nanoparticles arrayed with these three antigens on the capsid surface of the bacteriophage nanoparticles. These bivalent immunogenic compositions are able to elicit robust immune response in a subject administered said the bivalent immunogenic compositions and provide protection to the subject against sequential or simultaneous challenge with both anthrax and plague pathogens.

公开(公告)号：US20180264102A1

公开(公告)日：2018-09-20

申请号：US15892772

申请日：2018-02-09

Applicant: The Catholic University of America

Inventor： Venigalla B. RAO

IPC: A61K39/295 ,  C07K19/00 ,  C07K14/24 ,  C07K14/32 ,  C07K14/005 ,  A61K39/385 ,  A61K39/07

Abstract: Bivalent immunogenic compositions against anthrax and plague are disclosed herein. One bivalent immunogenic composition comprises a triple fusion protein containing three antigens, F1 and V from Yersinia pestis and PA antigen from Bacillus anthracia fused in-frame and retaining structural and functional integrity of all three antigens. Another bivalent immunogenic composition comprises bacteriophage nanoparticles arrayed with these three antigens on the capsid surface of the bacteriophage nanoparticles. These bivalent immunogenic compositions are able to elicit robust immune response in a subject administered said the bivalent immunogenic compositions and provide protection to the subject against sequential or simultaneous challenge with both anthrax and plague pathogens.