Immunogens comprising human immunodeficiency virus V1/V2 polypeptides
Inventors
Haynes, Barton F. • Liao, Huaxin • Kim, Jerome • Michael, Nelson • Zolla-Pazner, Susan B.
Assignees
New York University NYU • Duke University • US Army Medical Research and Development Command
Publication Number
US-9988424-B2
Publication Date
2018-06-05
Expiration Date
2032-12-05
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Abstract
The invention is generally directed to V1V2 immunogens.
Core Innovation
The invention provides V1V2 immunogens for use as an HIV-1 vaccine, including methods of making and using such immunogens to effectively induce immune responses against HIV-1 envelope V1V2 region.
It addresses the problem of modest efficacy (31.2%) and short duration of protection of the current RV144 HIV-1 vaccine, and the need to improve antibody immune response, focusing on antibodies that bind to unmutated ancestors and intermediates of the clonal lineage of broadly neutralizing antibodies to enhance protective response.
The invention includes multiple designs of HIV-1 V1V2 immunogens (including AE.A244 constructs with Ig leader and tags), characterized by superior antigenicity including binding to vaccine-induced and broadly neutralizing antibodies and their precursors, and formulation with carriers and adjuvants for eliciting effective antibody responses in human and non-human primates.
Claims Coverage
The claims include four independent inventive features related to HIV-1 V1V2 polypeptides and associated compositions and uses.
V1V2 polypeptides comprising specific HIV-1 sequences
Polypeptides comprising sequences corresponding to AE.A244 V1/V2, AE.A244 V1/V2tag, A.Q23V1/V2, or A.Q23V1/V2tag (designated by specific SEQ ID NOs).
Pharmaceutical compositions comprising V1V2 polypeptides and carriers
Compositions combining any claimed V1V2 polypeptides with a carrier, optionally further comprising an adjuvant to enhance immune response.
Methods of inducing antibodies to HIV-1 V1V2 region
Methods of inducing antibodies to the V1V2 region of HIV-1 env gp120 in a subject by administering compositions comprising the claimed V1V2 polypeptides.
Compositions consisting essentially of specific V1V2 peptides and carriers
Compositions where the polypeptide consists essentially of peptides AE.A244 V1/V2 or AE.A244 V1/V2tag along with a carrier, for use in antibody induction.
The claims cover specific V1V2 polypeptides, compositions comprising them with carriers and adjuvants, and methods of immunizing subjects to induce antibodies against HIV-1 V1V2 region.
Stated Advantages
Provides new vaccine immunogens that induce high titers of responses to HIV-1 Env V1V2.
Designs induce binding to both vaccine-induced and broad neutralizing antibodies and their precursors.
Capable of binding transmitted founder virus sequences and various HIV-1 clades for multivalent immunogen development.
Formulated for diverse delivery methods including DNA, viral vectors, protein boosts with various adjuvants and administration routes.
Monoclonal antibodies derived (CH58, CH59) show neutralization of tier 1 HIV-1 strains and mediate ADCC, suggesting functional roles in protection.
Documented Applications
Use as an HIV-1 vaccine immunogen to induce antibodies targeting the V1V2 region of the gp120 envelope protein.
Use of CH58, CH59 monoclonal antibodies or similar specificity antibodies for preventing or treating HIV-1 infection.
Formulation of immunogens for DNA vaccines, recombinant viral and bacterial vectors, or protein boosts with adjuvants in human and animal subjects.
Employing the immunogens and antibodies to reduce viral load and mediate protective immunity in infected or at-risk subjects.
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