Methods of inducing an immune response against HIV-1 using recombinant envelopes with improved coverage
Inventors
Kim, Jerome • Rolland, Morgane • Korber, Bette T. • Haynes, Barton F.
Assignees
Henry M Jackson Foundation for Advancedment of Military Medicine Inc • Duke University • Triad National Security LLC • United States Department of the Army
Publication Number
US-10906941-B2
Publication Date
2021-02-02
Expiration Date
2034-04-15
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Abstract
The present invention relates, in general, to human immunodeficiency virus-1 (HIV-1) particular, to a polyvalent vaccine for HIV-1 and to methods of making and using same.
Core Innovation
The present invention relates to a polyvalent vaccine for human immunodeficiency virus-1 (HIV-1) and methods of making and using the same. It addresses the need for a safe, practical, and effective HIV-1 vaccine to reduce the global spread of HIV-1, particularly improving vaccine-induced immune response against diverse HIV-1 envelope variants.
The problem being solved is the limited efficacy and coverage of existing HIV-1 vaccines, such as the RV144 trial vaccine, which showed only about 31.2% efficacy. This vaccine used specific HIV-1 envelopes that did not fully account for the epitope diversity in the V2 region of HIV-1 in the Thai population, limiting immune coverage and protective response.
The invention focuses on identifying and using recombinant HIV-1 envelope immunogens, including envelopes AA104.0, AA107.0, and AA058.1, alone or in combination with original RV144 vaccine envelopes, to improve coverage of epitope diversity, particularly in the V2 region. These envelopes are designed with specific deletions at the N-terminus (gp120 delta N-terminus) and are recombinant proteins or encoded by nucleic acids optimized for expression, optionally formulated with adjuvants such as Toll-like receptor 4 agonist glucopyranosyl lipid adjuvant-stable emulsion (GLA/SE).
Methods of inducing and boosting immune responses involve administering these compositions, either alone or combined with other envelopes used in the RV144 trial, such as B.6240 gp120D11 and A244 gp120 D11. The compositions can be administered in various regimens with the aim of enhancing vaccine efficacy through improved immune recognition and activity against HIV-1 envelopes in diverse populations.
Claims Coverage
The patent includes four independent claims outlining methods of inducing immune responses using recombinant HIV-1 envelope polypeptides with specific sequences and structural features.
Use of recombinant HIV-1 polypeptides comprising specific envelope sequences after the signal peptide
Administering compositions that include recombinant HIV-1 polypeptides comprising all consecutive amino acids immediately after the signal peptide from envelopes AA104.0 (positions 30-846 SEQ ID NO:1), AA107.0 (30-861 SEQ ID NO:2), AA058.1 (30-856 SEQ ID NO:3), or combinations thereof, in an amount sufficient to induce an immune response.
Use of gp120Delta N-terminus recombinant polypeptides from specific envelopes
Administering compositions comprising gp120Delta N-terminus recombinant polypeptides consisting of amino acids 41-501 in SEQ ID NO:1 (AA104.0), 41-509 in SEQ ID NO:2 (AA107.0), or 41-511 in SEQ ID NO:3 (AA058.1), produced recombinantly, to induce an immune response.
Combination of multiple gp120Delta N-terminus recombinant polypeptides for immune induction
Administering compositions comprising all three gp120Delta N-terminus recombinant polypeptides—AA104.0 (41-501), AA107.0 (41-509), and AA058.1 (41-511)—produced recombinantly, to induce an immune response.
Use of single gp120Delta N-terminus recombinant polypeptide to induce immune response
Administering a composition comprising the AA104.0 gp120Delta N-terminus recombinant polypeptide (41-501 SEQ ID NO:1), produced recombinantly, in an amount sufficient to effect immune induction.
The independent claims cover methods of inducing immune responses by administering recombinant HIV-1 envelope polypeptides with specified sequences and deletions, used singly or in combination, optionally incorporating known HIV-1 envelope proteins and adjuvants to enhance immunogenicity and vaccine coverage.
Stated Advantages
Improved coverage of epitope diversity in the HIV-1 V2 region in the Thai population compared to existing vaccines.
Induction of high titers of V1V2 and other CRF_01AE gp120 region antibody responses, potentially leading to enhanced protection.
Inclusion of envelopes that provide complementary coverage to existing vaccine strains, addressing viral genetic variability.
The ability to formulate the vaccine with potent adjuvants such as TLR4 agonists to boost immune response.
Potential for improved antibody-dependent cellular cytotoxicity (ADCC) and neutralization breadth as shown in animal studies.
Documented Applications
Use as a prophylactic HIV-1 vaccine to induce or boost immune responses against diverse HIV-1 envelope variants, especially targeting epitope diversity in the V2 region.
Immunization regimens combining ALVAC-HIV primes followed by recombinant envelope boosts formulated with adjuvants, following or improving upon RV144 trial protocols.
Administration to human subjects to generate an immune response that may reduce viral load in infected individuals and prevent or attenuate HIV-1 infection.
Combination vaccination strategies employing multiple recombinant envelopes including AA104.0, AA107.0, and AA058.1, optionally together with known envelope proteins from the RV144 vaccine trial.
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