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US 12,053,519 B2Granted
HIV-1 Env fusion peptide nanoparticle carrier conjugates and their use
AssigneeThe United States of America, as represented by the Secretary, Department of Health and Human Services
InventorsPeter Kwong, Li Ou, John Mascola, Baoshan Zhang, Kai Xu, Wing-Pui Kong, Yaroslav Tsybovsky, Cara W. Chao, Jeffrey Boyington, Yiran Wang
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Abstract
Embodiments of immunogenic conjugates including the HIV-1 Env fusion peptide and methods of their use and production are disclosed. In several embodiments, the immunogenic conjugates can be used to generate an immune response to HIV-1 Env in a subject, for example, to treat or prevent an HIV-1 infection in the subject.
Claims16
An immunogenic conjugate, comprising:
- a self-assembling protein-nanoparticle carrier comprising a multimer of fusion proteins, wherein each fusion protein comprises a self-assembling protein nanoparticle subunit fused to a heterologous carrier protein, and wherein the fusion proteins self-assemble to form the self-assembling protein-nanoparticle carrier;
- and
- HIV-1 Env fusion peptides conjugated to the self-assembling protein-nanoparticle carrier, wherein the HIV-1 Env fusion peptides comprise, from the N-terminus, the amino acid sequence of residue 512 to one of residues 514-521 of a human immunodeficiency virus type 1 (HIV-1) Envelope (Env) protein according to the HXB2 numbering system;
- and
- wherein the immunogen elicits an immune response to HIV-1 Env.
2 more elements
A recombinant self-assembling nanoparticle subunit, comprising:
- a lumazine synthase nanoparticle subunit comprising cysteine substitutions to introduce one or more non-native disulfide bonds to increase stability of the nanoparticle, wherein the cysteine substitutions comprise 121C and 131C substitutions, 121CG and 131C substitutions, 121GC and 131C substitutions, 7C and 40C substitutions, 3C and 50C substitutions, 82C and 131CG substitutions, 5C and 52C substitutions, or 95C and A101C substitutions, or a combination thereof, wherein residue numbering corresponds to a reference lumazine synthase subunit set forth as SEQ ID NO:
- 25;
- an encapsulin nanoparticle subunit comprising cysteine substitutions to introduce one or more non-native disulfide bonds to increase stability of the nanoparticle, wherein the cysteine substitutions comprise 53C and 94C substitutions, 53C and 96C substitutions, or 146C and 185C substitutions, or a combination thereof, wherein residue numbering corresponds to a reference encapsulin subunit set forth as SEQ ID NO:
- 43;
- an acinetobacter phage AP205 protein nanoparticle subunit comprising cysteine substitutions to introduce one or more non-native disulfide bonds to increase stability of the nanoparticle, wherein the cysteine substitutions comprise a T81C substitution, 53C and 100C substitution, or 82C and 80C substitutions, or a combination thereof, wherein residue numbering corresponds to a reference acinetobacter phage AP205 protein subunit set forth as SEQ ID NO:
- 316;
- or
- a Hepatitis B capsid protein nanoparticle subunit comprising cysteine substitutions to introduce one or more non-native disulfide bonds to increase stability of the nanoparticle, wherein the cysteine substitutions comprise 25C and 127C substitutions, 14C and 36C substations, 29C and 127C substitutions, 18C and 36C substitutions, or 29C and 127C substitutions, or a combination thereof, wherein residue numbering corresponds to a reference Hepatitis B capsid protein subunit set forth as SEQ ID NO:
- 321.
6 more elements
A recombinant self-assembling nanoparticle subunit, comprising:
- a ferritin nanoparticle subunit comprising or consisting of the amino acid sequence set forth as any one of SEQ ID NOs:
- 258-305;
- a lumazine synthase nanoparticle subunit comprising or consisting of the amino acid sequence set forth as any one of SEQ ID NOs:
- 306-312;
- an encapsulin nanoparticle subunit comprising or consisting of the amino acid sequence set forth as any one of SEQ ID NOs:
- 313-315;
- a Acinetobacter phage AP205 protein nanoparticle subunit comprising or consisting of the amino acid sequence set forth as any one of SEQ ID NOs:
- 317-320;
- or
- a Hepatitis B capsid protein nanoparticle subunit comprising or consisting of the amino acid sequence set forth as any one of SEQ ID NOs:
- 322-326.
8 more elements
Dependencies are inferred from the claim text.