Recombinant HIV compositions and uses thereof in animal models
Inventors
Ruprecht, Ruth M. • Lakhashe, Samir K.
Assignees
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Publication Number
US-11684666-B2
Publication Date
2023-06-27
Expiration Date
Abstract
Provided here are certain recombinant HIV compositions and animal models to evaluate prophylactic and therapeutic antiviral compositions.
Core Innovation
The invention provides a chimeric HIV composition comprising a nucleotide sequence of SEQ ID NO: 1 and uses this composition to establish a human immunodeficiency virus infection in a non-human primate. The non-human primate is provided with a weakened immune response resulting from administration of an IFN type 1 receptor antagonist. The approach supports infection, adaptation, and establishment of viral reservoirs.
The chimeric HIV composition corresponds to a recombinant simian-tropic HIV clade C, stHIV-C8457, built from HIV1084i with SIVmac239 vif and an HIV-C env background. The document describes use of pig-tailed macaques and states that immune weakening can be enhanced by CD8+ cell depletion and optionally B cell depletion. The resulting model reports exclusive CCR5 tropism and replication competence in PBMC and in vivo contexts.
The document additionally describes an adaptation strategy that selects viral progeny with improved fitness under innate immune pressure. It reports long-lasting viremia in IFN-1 antagonist-treated animals even after CD8+ reemergence. The described model is positioned for preclinical evaluation of HIV-1 vaccines and anti-HIV compounds, and it is associated with the presence and evolution of viral quasispecies/variants and viral reservoirs.
Claims Coverage
The partial content contains three independent claims: a method for developing HIV infection in a non-human primate, a method for evaluating an anti-HIV compound, and a method for evaluating an HIV vaccine. Across these independent claims, the core claim structure uses immune weakening by an IFN type 1 receptor antagonist, exposure to a chimeric HIV composition containing SEQ ID NO: 1, and subsequent evaluation or administration, with monitoring of immune cell changes for compound and vaccine evaluation.
Developing HIV infection via IFN type 1 receptor antagonist and SEQ ID NO: 1 chimeric composition
Providing a non-human primate with weakened immune response being result of administration of IFN type 1 receptor antagonist; and exposing the non-human primate to a chimeric HIV composition comprising a nucleotide sequence of SEQ ID NO: 1.
Evaluating an anti-HIV compound with IFN type 1 receptor antagonist and SEQ ID NO: 1
Providing a non-human primate with weakened immune response being result of administration of IFN type 1 receptor antagonist; exposing the non-human primate to a chimeric HIV composition comprising a nucleotide sequence of SEQ ID NO: 1; administering an anti-HIV compound to the exposed non-human primate; and monitoring the exposed non-human primate for changes in immune cells of the exposed non-human primate in response to the anti-HIV compound.
Evaluating an HIV vaccine with IFN type 1 receptor antagonist and SEQ ID NO: 1
Providing a non-human primate with weakened immune response being result of administration of IFN type 1 receptor antagonist; exposing the non-human primate to a chimeric HIV composition comprising a nucleotide sequence of SEQ ID NO: 1; administering a HIV vaccine to the exposed non-human primate; and monitoring the exposed non-human primate for changes in immune cells of the exposed non-human primate in response to the vaccine.
Across the independent claims, the shared inventive elements are immune weakening by administration of an IFN type 1 receptor antagonist in a non-human primate and exposure to a chimeric HIV composition comprising the nucleotide sequence of SEQ ID NO: 1. The anti-HIV and vaccine claims further add administration of the respective agent and monitoring for changes in immune cells in response.
Stated Advantages
Enables development of an HIV infection in a non-human primate.
Supports infection, adaptation, and establishment of viral reservoirs.
Reports exclusive CCR5 tropism and replication competence in PBMC and in vivo.
Shows long-lasting viremia in IFN-1 antagonist-treated animals even after CD8+ reemergence.
Provides a model positioned for preclinical evaluation of HIV-1 vaccines and anti-HIV compounds.
Documented Applications
Preclinical evaluation of HIV-1 vaccines.
Preclinical evaluation of anti-HIV compounds.
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