HIV vaccines comprising one or more population episensus antigens
Inventors
Bruening, Eric • Frueh, Klaus • Picker, Louis • Korber, Bette T. M. • Theiler, James • MARSHALL, Emily
Assignees
Oregon Health and Science University • Los Alamos National Security LLC • Triad National Security LLC • Vir Biotechnology Inc
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Publication Number
US-10894078-B2
Publication Date
2021-01-19
Expiration Date
Abstract
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.
Core Innovation
The disclosed content provides HIV-1 vaccine compositions designed using the EpiGraph computational approach. EpiGraph designs population episensus antigens, including episensus and fusion variants, and can optionally include tailored antigens matched to an individual’s infecting viral sequences.
A population episensus antigen design concept is described together with epitope-graph optimization for episensus coverage and cocktail/complementary coverage. The optimization models epitope coverage in an epitope-graph framework and addresses k-mers, consistency, gaps/placeholders, and sequential or complementary antigen optimization.
The disclosed claims are directed to vectors using a human cytomegalovirus (HCMV) backbone or a rhesus cytomegalovirus (RhCMV) backbone. The backbone comprises a nucleic acid sequence encoding a fusion antigen comprising an HIV-derived antigen sequence specified by SEQ ID NOs, and in one independent claim the HCMV backbone lacks the UL130-128 gene region and the UL82 gene encoding the tegument protein pp71.
Claims Coverage
The provided excerpt contains two independent claims. Each independent claim defines a viral vector with an HCMV or RhCMV backbone encoding a fusion antigen specified by a particular SEQ ID NO, with one independent claim additionally requiring deletion of the UL130-128 gene region and the UL82 gene encoding pp71.
Fusion antigen encoded by an HCMV or RhCMV backbone
A vector comprising a human cytomegalovirus (HCMV) backbone or a rhesus cytomegalovirus (RhCMV) backbone, wherein the HCMV or RhCMV backbone comprises a nucleic acid sequence encoding a fusion antigen comprising the amino acid sequence of a specified SEQ ID NO.
HCMV backbone lacking UL130-128 and UL82/pp71
A vector comprising a human cytomegalovirus (HCMV) backbone, wherein the HCMV backbone comprises a nucleic acid sequence encoding a fusion antigen comprising the amino acid sequence of a specified SEQ ID NO, and the HCMV backbone lacks the UL130-128 gene region and the UL82 gene encoding the tegument protein pp71.
Across the independent claims, inventive coverage centers on engineered cytomegalovirus vectors whose backbone encodes an HIV-derived fusion antigen defined by a specified SEQ ID NO, with one independent claim further limiting the backbone by omitting UL130-128 and UL82/pp71.
Stated Advantages
Improved epitope coverage for tailored and EpiGraph strategies versus consensus, natural, and mosaic baselines.
Documented Applications
Immunogenicity testing in rhesus models using CMV vectors expressing EpiGraph-designed antigens, including assessment of effector memory T cell response [procedural detail omitted for safety].
Inducing an anti-HIV-1 immune response in a subject by administering a vector comprising an HCMV or RhCMV backbone encoding a fusion antigen as recited in the claims.
Inducing an anti-HIV-1 effector memory T cell response in a subject by administering an effective amount of the claimed vector.
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