MHC class I associated peptides for prevention and treatment of zika virus
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Publication Number
US-11426457-B2
Publication Date
2022-08-30
Expiration Date
Abstract
The invention provides a vaccine composition comprising a flavivirus peptide comprising one or more CD8+ T cell C1 epitopes, wherein the peptide is attached to a nanoparticle.
Core Innovation
The invention relates to a flavivirus vaccine against Zika virus that uses CD8+ T cell epitopes. The vaccine comprises flavivirus peptides that include at least the CD8+ T cell epitope set out in SEQ ID NO:11, where the epitopes are presented in the context of MHC class I and are intended to induce CTL responses.
A key aspect is cross-protection across flaviviruses by using conserved cross-flavivirus epitopes. The document describes that the conserved MHC class I-presented peptides can provide coverage across different HLA supertypes and can support protection against Dengue virus and West Nile virus in addition to Zika virus.
The vaccine peptides are formulated as peptides, including optionally peptide variants, and are attached to nanoparticles to enhance T-cell/CTL responses. The document further describes nanoparticle attachment, including gold nanoparticles, calcium phosphate nanoparticles, and silicon nanoparticles, with optional nanoparticle coating concepts, together with the rationale that this may reduce the need for adjuvant/virus and mitigate adverse effects.
Claims Coverage
The independent claim covers a vaccine composition defined by three inventive features: a flavivirus peptide containing at least the CD8+ T cell epitope set out in SEQ ID NO:11, a peptide length of about 8 to about 40 amino acids, and attachment of the flavivirus peptide to a nanoparticle. Dependent claims add specific nanoparticle material options, define the attachment via a linker, and further limit epitope conservation across flaviviruses and specifically across Zika, West Nile, and/or Dengue viruses.
Nanoparticle-attached flavivirus CD8+ T cell peptide
A vaccine composition comprising a flavivirus peptide comprising at least the CD8+ T cell epitope set out in SEQ ID NO:11, wherein the flavivirus peptide is about 8 to about 40 amino acids in length, and wherein the flavivirus peptide is attached to a nanoparticle.
Selected nanoparticle materials for peptide attachment
The vaccine composition wherein the nanoparticle is selected from gold nanoparticles, calcium phosphate nanoparticles, or silicon nanoparticles, optionally with gold nanoparticles coated with alpha-galactose and/or beta-GlcNHAc.
Linker-mediated attachment to nanoparticles
The vaccine composition wherein the flavivirus peptide is attached to a nanoparticle using a linker.
Conservation of the CD8+ T cell epitope across flaviviruses
The vaccine composition in which the CD8+ T cell epitope is conserved across flaviviruses.
Conservation of the CD8+ T cell epitope across Zika, West Nile, and/or Dengue
The vaccine composition defined so that its CD8+ T cell epitope is conserved across Zika viruses, West Nile viruses and/or Dengue viruses.
Overall, the claim set centers on a flavivirus vaccine composition that uses a CD8+ T cell epitope (SEQ ID NO:11) within a specified peptide length range and attaches the peptide to a nanoparticle, with dependent claims specifying nanoparticle types, linker attachment, and conservation of the epitope across flaviviruses and specifically across Zika, West Nile, and/or Dengue viruses.
Stated Advantages
Enhance T-cell/CTL responses.
Reduce the need for adjuvant/virus.
Mitigate adverse effects.
Provide cross-protection via conserved MHC class I-presented peptides.
Documented Applications
A flavivirus vaccine against Zika virus that can provide cross-protection to Dengue virus and West Nile virus using conserved CD8+ T cell epitopes.
Cross-protection grounded in conserved MHC class I-presented peptide epitopes with coverage across different HLA supertypes.
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