Abstract: Viruses, and particularly genetically engineered, replication deficient viruses such as adenoviruses, poxviruses, MVA viruses, and baculoviruses which encode one or more antigens of interest, such as TB, malarial, and HIV antigens, are spray dried with a mannitol-cyclodextrin-trehalose-dextran (MCTD) to form a powder where the viability of the viruses are maintained at a suitable level for mass vaccinations after spray drying, and where the viability of the viruses are maintained at suitable level over a period of storage time, even in the presence of humidity.
Abstract: Recombinant Mycobacteria (rMyc) which contain sequences encoding a heparin-binding hemagglutinin (HBHA) fusion protein are provided, as are methods of making and using the rMyc and the fusion protein. The fusion protein includes an amino terminal mycobacterial antigen Ag85B leader peptide and transcription of the fusion protein is driven by an Ag85B promoter sequence. The recombinant fusion protein is produced in abundance by the rMyc, is post-translationally methylated, and is highly antigenic.
Type:
Application
Filed:
April 16, 2012
Publication date:
October 15, 2015
Applicants:
Aeras Global TB Vaccine Foundation, Institut National De La Sante Et De La Recherche Medicale (INSERM)
Inventors:
John Fulkerson, Michael Brennan, Kamalakannan Velmurugan, Camille Locht
Abstract: Malaria vaccines based on polyepitope constructs that elicit cell-mediated immunity against a broad spectrum of malaria parasites and which cover the majority of HLA alleles are provided. Epitopes in the polyepitope constructs are from regions of the Plasmodium falciparum circumsporozoite protein (CSP) known to contain CD4 and CD8 T cell epitopes, and include both epitopes from highly variable and highly conserved regions of CSP.
Type:
Grant
Filed:
January 12, 2009
Date of Patent:
May 20, 2014
Assignee:
Aeras Global TB Vaccine Foundation
Inventors:
Avigdor Shafferman, Anat Zvi, John Fulkerson, Jerald C. Sadoff
Abstract: Bacterial delivery systems with improved transgene expression are provided. The recombinant bacterial delivery systems deliver transgenes of interest and suppressors of the eukaryotic Type I interferon response to eukaryotic cells. Suppression of the eukaryotic Type I interferon response allows improved expression of the encoded transgene.
Type:
Grant
Filed:
April 8, 2013
Date of Patent:
February 25, 2014
Assignee:
Aeras Global TB Vaccine Foundation
Inventors:
Jerald C. Sadoff, Mohamad F. Jamiluddin, Ravi P. Anantha, John F. Fulkerson, Jr.
Abstract: The invention relates to vaccines comprising recombinant vectors, such as recombinant adenoviruses. The vectors comprise heterologous nucleic acids encoding for at least two antigens from one or more tuberculosis-causing bacilli. Also described is the use of specific protease recognition sites linking antigens through which the encoded antigens are separated upon cleavage. After cleavage, the antigens contribute to the immune response in a separate manner. The recombinant vectors may comprise a nucleic acid encoding the protease cleaving the linkers and separating the antigens. Further described is the use of genetic adjuvants encoded by the recombinant vectors, wherein such genetic adjuvants may also be cleaved through the presence of the cleavable linkers and the specific protease.
Type:
Grant
Filed:
May 31, 2011
Date of Patent:
December 17, 2013
Assignees:
Aeras Global TB Vaccine Foundation, Crucell Holland B.V
Inventors:
Menzo Jans Emco Havenga, Ronald Vogels, Jerald C. Sadoff, David Hone, Yasir Abdul Wahid Skeiky, Katarina Rado{hacek over (s)}evic
Abstract: Bacterial delivery systems with improved transgene expression are provided. The recombinant bacterial delivery systems deliver transgenes of interest and suppressors of the eukaryotic Type I interferon response to eukaryotic cells. Suppression of the eukaryotic Type I interferon response allows improved expression of the encoded transgene.
Type:
Application
Filed:
April 8, 2013
Publication date:
August 29, 2013
Applicant:
Aeras Global TB Vaccine Foundation
Inventors:
Jerald C. Sadoff, Mohamad F. Jamiluddin, Ravi P. Anantha, John F. Fulkerson, JR.
Abstract: Bacterial delivery systems with improved transgene expression are provided. The recombinant bacterial delivery systems deliver transgenes of interest and suppressors of the eukaryotic Type I interferon response to eukaryotic cells. Suppression of the eukaryotic Type I interferon response allows improved expression of the encoded transgene.
Type:
Grant
Filed:
December 10, 2010
Date of Patent:
April 9, 2013
Assignee:
Aeras Global TB Vaccine Foundation
Inventors:
Jerald C. Sadoff, Mohamad F. Jamiluddin, Ravi P. Anantha, John F. Fulkerson, Jr.
Abstract: A vaccine against Mycobacteria tuberculosis (Mtb) is provided. The vaccine comprises a recombinant Bacille Calmette-Guerin (BCG) subunit-based vaccine in which one or more Mtb antigens and one or more Mtb resuscitation or reactivation antigens are overexpressed, and in which at least a portion of the DosR regulon is up-regulated. The vaccine is protective against active Mtb infection both pre- and post-exposure to Mtb, and thus prevents disease symptoms due to the recurrence of a latent Mtb infection.
Type:
Grant
Filed:
November 13, 2009
Date of Patent:
January 29, 2013
Assignee:
Aeras Global TB Vaccine Foundation
Inventors:
Avigdor Shafferman, Anat Zvi, Naomi Ariel, John Fulkerson, Roaggai Sun, Rosemary Chang, Jerald C. Sadoff
Abstract: Described are vaccines comprising recombinant vectors, such as recombinant adenoviruses. The vectors comprise heterologous nucleic acids encoding at least two antigens from one or more tuberculosis-causing bacilli. Also described is the use of specific protease recognition sites linking antigens through which the encoded antigens are separated upon cleavage. After cleavage, the antigens contribute to the immune response in a separate manner. The recombinant vectors may comprise a nucleic acid encoding the protease cleaving the linkers and separating the antigens. Also described is the use of genetic adjuvants encoded by the recombinant vectors, wherein such genetic adjuvants may also be cleaved through the presence of the cleavable linkers and the specific protease.
Type:
Grant
Filed:
May 31, 2011
Date of Patent:
June 19, 2012
Assignees:
Crucell Holland B.V., Aeras Global TB Vaccine Foundation
Inventors:
Menzo Jans Emco Havenga, Ronald Vogels, Jerald C. Sadoff, David Hone, Yasir Abdul Wahid Skeiky, Katarina Rado{hacek over (s)}evic
Abstract: Bacterial packaging strains useful for generating recombinant double-stranded RNA nucleocapsids (rdsRNs) are provided. The packaging strains are useful for the production of RNA encoding vaccine antigens, bioactive proteins, immunoregulatory proteins, antisense RNAs, and catalytic RNAs in eukaryotic cells or tissues. Recombinant ssRNA is introduced into the strains and packaged to form rdsRNs de novo.
Type:
Grant
Filed:
November 23, 2005
Date of Patent:
November 8, 2011
Assignee:
Aeras Global TB Vaccine Foundation
Inventors:
David Hone, John Fulkerson, Jerald C. Sadoff, David Onyabe, Michele Stone
Abstract: Mycobacterium strains that have an enhanced ability to elicit a MHC-Class I-restricted CD8+ T cell immune response are provided. The Mycobacterium strains are genetically engineered to express: a endosomalytic protein that is active at neutral pH (e.g. Perfringolysin O), permitting escape of the Mycobacterium from endosomes into the cytoplasm of the cell; and antigens of interest, such as tuberculosis antigens. The invention also provides vaccine preparations containing such Mycobacterium strains.
Type:
Grant
Filed:
December 31, 2009
Date of Patent:
October 25, 2011
Assignee:
Aeras Global TB Vaccine Foundation
Inventors:
Ronggai Sun, David Michael Hone, Jerald C. Sadoff
Abstract: The invention relates to vaccines comprising recombinant vectors, such as recombinant adenoviruses. The vectors comprise heterologous nucleic acids encoding for at least two antigens from one or more tuberculosis-causing bacilli. The invention also relates to the use of specific protease recognition sites linking antigens through which the encoded antigens are separated upon cleavage. After cleavage, the antigens contribute to the immune response in a separate manner. The recombinant vectors may comprise a nucleic acid encoding the protease cleaving the linkers and separating the antigens. The invention furthermore relates to the use of genetic adjuvants encoded by the recombinant vectors, wherein such genetic adjuvants may also be cleaved through the presence of the cleavable linkers and the specific protease.
Type:
Grant
Filed:
November 15, 2005
Date of Patent:
September 6, 2011
Assignees:
Crucell Holland B.V., Aeras Global TB Vaccine Foundation
Inventors:
Menzo J. E. Havenga, Ronald Vogels, Jerald Sadoff, David Hone, Yasir A. W. Skeiky, Katarina Radosevic
Abstract: A vaccine for treating or preventing the establishment of latent tuberculosis infections is provided. The vaccine comprises a recombinant mycobacterium that overexpresses the transcription factor DosR, at a level sufficient to induce production of the dosR regulon genes or proteins. A host to whom the vaccine is administered mounts an immune response to the dosR regulon proteins and is thus protected from the establishment, persistence or reactivation of latent tuberculosis.
Type:
Grant
Filed:
November 13, 2007
Date of Patent:
May 3, 2011
Assignees:
Aeras Global TB Vaccine Foundation, The Board of Trustees of the Leland Stanford Junior University
Inventors:
Mario Alberto Flores-Valdez, Gary K. Schoolnik, Michel Klein, Jerald C. Sadoff, David Hone
Abstract: Bacterial delivery systems with improved transgene expression are provided. The recombinant bacterial delivery systems deliver transgenes of interest and suppressors of the eukaryotic Type I interferon response to eukaryotic cells. Suppression of the eukaryotic Type I interferon response allows improved expression of the encoded transgene.
Type:
Grant
Filed:
September 11, 2009
Date of Patent:
February 8, 2011
Assignee:
Aeras Global TB Vaccine Foundation
Inventors:
Jerald C. Sadoff, Mohamad F. Jamiluddin, Ravi P. Anantha, John F. Fulkerson, Jr.
Abstract: Recombinant Mycobacterium strains with improved vaccinal properties for use as vaccinating agents are provided. The parent strains of the recombinant Mycobacterium strains are selected for their potent immunogenicity. The Mycobacterium strains do not display antibiotic resistance, and do not exhibit horizontal transfer to gram-negative bacteria.
Type:
Grant
Filed:
May 31, 2007
Date of Patent:
November 9, 2010
Assignee:
Aeras Global TB Vaccine Foundation
Inventors:
Ronggai Sun, David Michael Hone, Jerald C. Sadoff
Abstract: A vaccine against Mycobacteria tuberculosis (Mtb) is provided. The vaccine comprises a recombinant Bacille Calmette-Guerin (BCG) subunit-based vaccine in which one or more Mtb antigens and one or more Mtb resuscitation or reactivation antigens are overexpressed, and in which at least a portion of the DosR regulon is up-regulated. The vaccine is protective against active Mtb infection both pre- and post-exposure to Mtb, and thus prevents disease symptoms due to the recurrence of a latent Mtb infection.
Type:
Grant
Filed:
November 27, 2007
Date of Patent:
March 2, 2010
Assignee:
Aeras Global TB Vaccine Foundation
Inventors:
Avigdor Shafferman, Anat Zvi, Naomi Ariel, John Fulkerson, Ronggai Sun, Rosemary Chang, Jerald C. Sadoff
Abstract: Mycobacterium strains that have an enhanced ability to elicit a Histocompatibility-Class I-restricted CD8+ T cell immune response are provided. The Mycobacterium strains are genetically engineered to express a endosomalytic protein that is active at neutral pH (e.g. Perfringolysin O), permitting escape of the Mycobacterium from endosomes into the cytoplasm of the cell. The invention also provides vaccine preparations containing the Mycobacterium strains.
Type:
Application
Filed:
November 23, 2005
Publication date:
February 25, 2010
Applicant:
AERAS GLOBAL TB VACCINE FOUNDATION
Inventors:
Ronggai Sun, David M. Hone, Jerald C. Sadoff
Abstract: Mycobacterium strains that have an enhanced ability to elicit a MHC-Class I-restricted CD8+ T cell immune response are provided. The Mycobacterium strains are genetically engineered to express: a endosomolytic protein that is active at neutral pH (e.g. Perfringolysin O), permitting escape of the Mycobacterium from endosomes into the cytoplasm of the cell; and antigens of interest, such as tuberculosis antigens. The invention also provides vaccine preparations containing such Mycobacterium strains.
Type:
Grant
Filed:
May 31, 2007
Date of Patent:
February 23, 2010
Assignee:
Aeras Global TB Vaccine Foundation
Inventors:
Ronggai Sun, David Michael Hone, Jerald C. Sadoff
Abstract: Recombinant Mycobacterium strains with improved vaccinal properties for use as vaccinating agents are provided. The parent strains of the recombinant Mycobacterium strains are selected for their potent immunogenicity. The Mycobacterium strains do not display antibiotic resistance, and do not exhibit horizontal transfer to gram-negative bacteria.
Type:
Grant
Filed:
November 29, 2005
Date of Patent:
December 1, 2009
Assignee:
Aeras Global TB Vaccine Foundation
Inventors:
Ronggai Sun, David Michael Hone, Jerald C. Sadoff
Abstract: Bacterial delivery systems with improved transgene expression are provided. The recombinant bacterial delivery systems deliver transgenes of interest and suppressors of the eukaryotic Type I interferon response to eukaryotic cells. Suppression of the eukaryotic Type I interferon response allows improved expression of the encoded transgene.
Type:
Grant
Filed:
September 12, 2007
Date of Patent:
October 27, 2009
Assignee:
Aeras Global TB Vaccine Foundation
Inventors:
Jerald C. Sadoff, Mohamad F. Jamiluddin, Ravi P. Anantha, John F. Fulkerson, Jr.