Other

National Jewish Health

Dartmouth College

Gongyi Zhang

Hong-Bing Shu

Liangguo Xu

Yingfang Liu

Ambrose Cheung

Elizabeth T Campbell

Adhar Manna

Konstantin Severinov

Seth A Darst

Leonid Minakin

To develop a universal and long-lasting influenza or other pathogens vaccine has been a mission impossible goal in the life science and health field. Applicants disclose, herein, vaccines prepared against SARS-COV-2, an influenza A strain vaccine prepared from a 1934 influenza virus (A/PR/8/34 H1N1, Puerto Roca, 1934), and an influenza B strain vaccine prepared from a 1940 influenza virus. The disclosed vaccine induces production of broadly neutralizing antibodies in mice. The presently disclosed vaccine is able to inhibit two other influenza A strains: a 2009 influenza H1N1 virus collected from Los Angeles (A/California/07/2009) and a 2014 influenza H3N2 virus collected from Hong Kong (A/Hongkong/4801/2014). Applicants also describe an influenza B strain vaccine prepared from a B strain virus from a 1940 patient in USA (B/L11/40). The B strain vaccine also produced broadly neutralizing antibodies, in this case against a B strain from Colorado 2017 (B/Colorado/2017). Applicant's methods and compositions are not only useful in creating influenza vaccines with broad activity against other influenza subtypes but also be efficient to generate long-lasting SARS-CoV-2 vaccines against emerging new variants either through recombined protein antigens from SARS-CoV-2 or inactivated SARS-CoV-2 virus.

Methods and compositions for a universal and long-lasting vaccine

Disclosed are TALL-1 and TALL-1 receptor protein homologues (agonists and antagonists) designed based on the three-dimensional structure of sTALL-1, eBCMA and eBAFF-R; agonist homologues of APRIL; methods of using wild-type APRIL to inhibit the activity of TALL-1; compositions comprising such homologues, nucleic acid molecules encoding such homologues, and therapeutic methods of using such compounds and compositions. Also disclosed are crystalline complexes of sTALL-1 and sTALL-1 in complex with either BCMA or BAFF-R; models of three-dimensional structures of such crystalline complexes and related structures, methods of drug design using any portion of such structures; methods of design and/or identification of regulatory peptides derived from the such structures; compounds identified by drug design using such structures; and the use of such compounds in therapeutic compositions and methods.

Three-dimensional structures of TALL-1 and its cognate receptors and modified proteins and methods related thereto

A novel sarR gene and sarR gene product which down regulates the expression of sarA and the resulting virulence determinants inis provided. Methods for modulating the expression of sarA and virulence determinants are also provided. A preferred embodiment of the present invention provides structural information relating to the gene product and enables the identification and formulation of lead compounds and reducements for treating and preventing infections byand related bacteria.

Compositions and methods for affecting virulence determinants in bacteria

A detailed three dimensional structure for a bacterial core RNA polymerase is provided. Crystals of the bacterial core RNA polymerase are also included in the invention. The present invention further provides procedures for identifying agents that can inhibit bacterial proliferation through the use of rational drug design predicated on the crystals and crystallographic data disclosed.

Crystal of bacterial core RNA polymerase and methods of use thereof

Growing community of inventors

Denver, CO, United States of America

Gongyi Zhang