Scaffolded hiv-1 vaccine immunogens
Abstract
The present invention provides novel scaffolded HIV-1 vaccine immunogens. Some of the scaffolded immunogens contain a soluble gp140 trimer linked to the N-terminus of the nanoparticle subunit and a T-helper epitope that is fused via a short peptide spacer to the C-terminus of the nanoparticle subunit. Some other immunogens of the invention contain a soluble gp140 trimer protein that is linked to a stable nanoparticle via a short peptide spacer that is a T-helper epitope. Some of the scaffolded immunogens contain a gp140 trimer immunogen presented on a nanoparticle platform formed with I3-01 protein, E2p, or variants of protein 1VLW. Also provided in the invention are nucleic acids that encode the various vaccine immunogens described herein, and expression vectors and host cells harboring the nucleic acids. The invention further provides methods of using the scaffolded HIV-1 vaccine immunogens for preventing or treating HIV infections.
Claims
exact text as granted — not AI-modified1 . A HIV-1 vaccine immunogen, comprising an HIV-1 Env-derived trimer protein presented on a self-assembling nanoparticle, wherein a T-helper epitope sequence (a) is fused to the C-terminus of the nanoparticle subunit while the HIV-1 trimer protein subunit is fused to the N-terminus of the nanoparticle subunit or (b) links the HIV-1 trimer protein to N-terminus of the nanoparticle subunit.
2 . The HIV-1 vaccine immunogen of claim 1 , wherein the T-helper epitope sequence comprises a sequence as shown in any one of SEQ ID NOs: 1-3, a conservatively modified variant or a substantially identical sequence thereof.
3 . The HIV-1 vaccine immunogen of claim 1 , wherein the self-assembling nanoparticle comprises a trimeric sequence.
4 . The HIV-1 vaccine immunogen of claim 1 , wherein subunit of the self-assembling nanoparticle is E2p, ferritin, or a conservatively modified variant or a substantially identical sequence thereof.
5 . The HIV-1 vaccine immunogen of claim 1 , wherein the HIV-1 Env-derived trimer protein is gp140.
6 . The HIV-1 vaccine immunogen of claim 1 , wherein the HIV-1 Env-derived trimer protein is an uncleaved prefusion-optimized (UFO) gp140 trimer.
7 . The HIV-1 vaccine immunogen of claim 6 , wherein the UFO gp140 trimer is a chimeric trimer comprising a modified gp41 ECTO domain from HIV-1 strain BG505.
8 . (canceled)
9 . A polynucleotide encoding the HIV-1 vaccine immunogen of claim 1 .
10 . A vector harboring the polynucleotide of claim 9 .
11 . A pharmaceutical composition, comprising the HIV-1 vaccine immunogen of claim 1 , and a pharmaceutically acceptable carrier.
12 . The pharmaceutical composition of claim 11 , further comprising an adjuvant.
13 . A method of preventing HIV-1 infection in a subject, comprising administering to the subject a therapeutically effective amount of the HIV-1 vaccine immunogen of claim 1 , thereby preventing HIV-1 infection in the subject.
14 . (canceled)
15 . A method of treating HIV-1 infection or eliciting an immune response against HIV-1 in a subject, comprising administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of the HIV-1 vaccine immunogen of claim 1 , thereby treating HIV-1 infection or eliciting an immune response against HIV-1 in the subject.
16 . (canceled)
17 . The HIV-1 vaccine immunogen of claim Error! Reference source not found, wherein the C-terminus of the nanoparticle subunit is fused to the N-terminus of the T-helper epitope via a short peptide spacer.
18 . The HIV-1 vaccine immunogen of claim 17 , wherein the HIV-1 trimer protein subunit is fused to the N-terminus of the nanoparticle subunit via a second peptide spacer.
19 . The HIV-1 vaccine immunogen of claim 17 , wherein the T-helper epitope sequence is encapsulated within the nanoparticle.Join the waitlist — get patent alerts
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