Oregon Health & Science University

Triad National Security, LLC

Vir Biotechnology, Inc.

International Aids Vaccine Initiative

International Aids Vaccine Initative, Inc.

Los Alamos National Security, LLC

Louis Picker

Scott G Hansen

Klaus Frueh

Jay A Nelson

Daniel Malouli

Thomas G Evans

Bette T M Korber

Dominick J Laddy

Ravi P Anantha

Aurelio M Bonavia

Eric Bruening

Emily Marshall

Patrizia Caposio

Guangwu Xu

Michael A Jarvis

Klaus Früh

Colin Powers

James Theiler

Jonah Sacha

Meaghan Hancock

Collin Powers

Jay Nelson

Klaus Fruh

Bette Tm Korber

Bette TM Korber

Provided are cytomegalovirus vectors encoding fusion proteins comprising(Mtb) antigens, nucleic acid molecules encoding the same, cytomegalovirus vectors comprising nucleic acid molecules, compositions comprising the same, and methods of eliciting an immune response against tuberculosis.

Recombinant cytomegalovirus vectors as vaccines for tuberculosis

Disclosed herein are cytomegalovirus vectors encoding fusion proteins comprising Mycobacterium tuberculosis (Mtb) antigens, nucleic acid molecules encoding the same, cytomegalovirus vectors comprising nucleic acid molecules, compositions comprising the same, and methods of eliciting an immune response against tuberculosis.

Human cytomegalovirus vectors comprising heterologous antigens are disclosed. The vectors derived from the TR strain, are ganciclovir sensitive, include active US2, US3, US6, US7 and UL131A genes, and have a deleterious or inactivating mutation in the UL82 gene preventing the expression of pp71.

Human cytomegalovirus comprising exogenous antigens

Provided herein are HIV-1 vaccines comprising a carrier and a population episensus antigen determined using the EpiGraph approach. Also provided are HIV-1 vaccines comprising a carrier, a population episensus antigen, and a tailored antigen. Also provided are methods of designing and producing an HIV-1 vaccine for a subject comprising designing vaccine antigens to optimally cover the diversity within a geographic area using an antigen amino acid sequence generated using the EpiGraph approach, and producing said designed vaccine antigen. Also provided are methods of inducing an effector memory T cell response comprising designing the one or more EpiGraph amino acid sequences, producing a vaccine comprising the one or more EpiGraph amino acid sequences and a vector, and administering the vaccine to a subject. Further provided are methods of treating HIV-1 in a subject comprising administering an effective amount of the described HIV-1 vaccines to the subject in need thereof.

HIV vaccines comprising one or more population episensus antigens

CMV vectors that lack active UL128, UL130, UL146 and UL147 proteins that may also comprise one or more microRNA regulatory elements (MRE) that restrict expression of the CMV are provided. Immunization with CMV vectors having the described features allows selection of different CD8+ T cell responses&#x2014;CD8+ T cells restricted by MHC-Ia, MHC-II, or by MHC-E.

Cytomegalovirus vectors eliciting T cells restricted by major histocompatibility complex E molecules

The present disclosure relates to recombinant rhesus cytomegalovirus (RhCMV) and human cytomegalovirus (HCMV) vectors encoding heterologous antigens, such as pathogen-specific antigens or tumor antigens, which may be used, for example, for the treatment or prevention of infectious disease or cancer. The recombinant RhCMV or HCMV vectors elicit and maintain high level cellular immune responses specific for the heterologous antigen while including deletions in one or more genes essential or augmenting for CMV replication, dissemination or spread.

Recombinant HCMV and RHCMV vectors and uses thereof

Methods of inducing a CD8+ T cell response to a heterologons antigen in which at least 10% of the CD8+ T cells are MHC-E restricted are disclosed. The method involves immunizing with a CMV vector that does not express UL128 and UL130 proteins. Also disclosed are recombinant CMV vectors comprising nucleic acids encoding a heterologous protein antigen, a UL40 protein, and a US28 protein but that do not express an active UL128 and UL130 protein. Also, disclosed are recombinant CMV vectors comprising nucleic acids encoding a heterologous protein antigen, but that do not express an active UL40 protein, UL128 protein, UL130 protein, and optionally a US28 protein. Also disclosed are recombinant CMV vectors comprising nucleic acids encoding a heterologous protein antigen, but that do not express an active US28 protein, UL128 protein, UL130 protein, and optionally a UL40 protein.

Methods and compositions useful in generating non canonical CD8+ T cell responses

The present disclosure provides cytomegalovirus vectors encoding fusion proteins comprising(Mtb) antigens, nucleic acid molecules encoding the same, cytomegalovirus vectors comprising nucleic acid molecules, compositions comprising the same, and methods of eliciting an immune response against tuberculosis.

Human cytomegalovirus vectors comprising heterologous antigens are disclosed. The vectors derived from the TR strain, are ganciclovir-sensitive, include active US2, US3, US6, US7 and UL131A genes, and have a deleterious or inactivating mutation in the UL82 gene preventing the expression of pp71.

Disclosed herein are recombinant CMV vectors which may comprise a heterologous antigen that can repeatedly infect an organism while inducing a CD8+ T cell response to immunodominant epitopes of the heterologous antigen. The CMV vector may comprise a deleterious mutation in the US11 glycoprotein or a homolog thereof.

CMV glycoproteins and recombinant vectors

Disclosed herein are recombinant CMV vectors comprising heterologous antigens and microRNA recognition elements to silence expression of CMV genes in the presence of microRNA derived from myeloid cells, an active UL128 protein and an active UL130 protein. Also disclosed are recombinant CMV vectors comprising heterologous antigens and microRNA recognition elements to silence expression of CMV genes in the presence of microRNA derived from myeloid cells, an inactive UL128 protein and an inactive UL130 protein. Also disclosed are methods of generating an unconventional immune response using these vectors. Such an immune response is characterized by generation of a CD8+ T cell response that is predominantly restricted by MHC-II.

CMV vectors comprising microRNA recognition elements

Disclosed are CMV vectors that lack active UL128, UL130, UL146 and UL147 proteins that may also comprise one or more microRNA regulatory elements (MRE) that restrict expression of the CMV. Immunization with the disclosed CMV vectors allow selection of different CD8+ T cell responses&#x2014;CD8+ T cells restricted by MHC-Ia, MHC-II, or by MHC-E.

Growing community of inventors

Portland, OR, United States of America

Louis Picker