Zika virus vaccines
AssigneeUniversity of Pittsburgh—Of the Commonwealth System of Higher Education
InventorsAndrea A. Gambotto, Eun Kim, Geza Erdos, Louis D. Falo, Jr.
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Abstract
Disclosed is an immunogen comprising a fusion protein, wherein the fusion protein comprises a Zika virus (ZIKV) envelope protein, optionally a signal peptide, and a multimerization domain. The signal peptide is a premembrane (prM) signal peptide, an IgG signal peptide, or a human secretory signal peptide hidden Markov model, and the multimerization domain is an immunoglobulin Fc domain, a T4 fibritin foldon trimerization domain, or a human collagen XV trimerization domain. Nucleic acids, vectors, and microneedle arrays including these compositions are disclosed. Methods of producing an immune response to ZIKV are also disclosed.
Claims72
An immunogen comprising a fusion protein, wherein the fusion protein comprises a Zika virus (ZIKV) envelope protein, a signal peptide, and a multimerization domain, wherein:
- the signal peptide is a human secretory signal peptide hidden Markov model, wherein the human secretory signal peptide hidden Markov model comprises an amino acid sequence at least 95% identical to SEQ ID NO:
- 2;
- and
- the multimerization domain is an immunoglobulin Fc domain, a T4 fibritin foldon trimerization domain, or a human collagen XV trimerization domain.
An immunogen comprising a fusion protein, wherein the fusion protein comprises a Zika virus (ZIKV) envelope protein, a signal peptide, and a multimerization domain, wherein:
- the signal peptide is an IgG signal peptide, wherein:
- a) the IgG signal peptide is a mouse IgG signal peptide comprising an amino acid sequence at least 95% identical to SEQ ID NO:
- 3;
- or
- b) the IgG signal peptide is a human IgG signal peptide comprising an amino acid sequence at least 95% identical to SEQ ID NO:
- 4,
- and wherein
- c) the multimerization domain is an immunoglobulin Fc domain, a T4 fibritin foldon trimerization domain, or a human collagen XV trimerization domain.
An immunogen comprising a fusion protein, wherein the fusion protein comprises a Zika virus (ZIKV) envelope protein, a signal peptide, and a multimerization domain, wherein:
- the signal peptide is a prM signal peptide, wherein the prM signal peptide is a human IgG signal peptide comprising an amino acid sequence at least 95% identical to SEQ ID NO:
- 5 and the multimerization domain is an immunoglobulin Fc domain, a T4 fibritin foldon trimerization domain, or a human collagen XV trimerization domain.
An immunogen comprising a fusion protein, wherein the fusion protein comprises a Zika virus (ZIKV) envelope protein, a signal peptide, and a multimerization domain, wherein:
- the signal peptide is a premembrane (prM) signal peptide, an IgG signal peptide, or a human secretory signal peptide hidden Markov model, and
- wherein the multimerization domain is an immunoglobulin Fc domain, and wherein the immunoglobulin Fc domain comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:
- 9, and wherein the immunoglobulin Fc domain forms a dimer in vivo.
An immunogen comprising a fusion protein, wherein the fusion protein comprises a Zika virus (ZIKV) envelope protein, a signal peptide, and a multimerization domain, wherein:
- the signal peptide is a premembrane (prM) signal peptide, an IgG signal peptide, or a human secretory signal peptide hidden Markov model, and
- wherein the multimerization domain is a T4 fibritin foldon trimerization domain, and wherein the T4 fibritin foldon trimerization domain comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:
- 10, wherein the fibritin foldon trimerization domain forms a trimer in vivo.
An immunogen comprising a fusion protein, wherein the fusion protein comprises a Zika virus (ZIKV) envelope protein, a signal peptide, and a multimerization domain, wherein:
- the signal peptide is a premembrane (prM) signal peptide, an IgG signal peptide, or a human secretory signal peptide hidden Markov model, and
- wherein the multimerization domain is the a human collagen XV trimerization domain, and wherein the human collagen XV trimerization domain comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:
- 11, wherein the human collagen XV trimerization domain forms a trimer in vivo.
An immunogen comprising a fusion protein, wherein the fusion protein comprises a Zika virus (ZIKV) envelope protein, a signal peptide, a multimerization domain, and a premembrane (prM) of ZIKV wherein:
- the signal peptide is a prM signal peptide, an IgG signal peptide, or a human secretory signal peptide hidden Markov model, and
- the multimerization domain is an immunoglobulin Fc domain, a T4 fibritin foldon trimerization domain, or a human collagen XV trimerization domain
- and the prM of ZIKV comprises an amino acid sequence at least 95% identical to SEQ ID NO:
- 8.
A dissolvable microneedle array for transdermal insertion into a subject
- for promoting an immune response against Zika virus (ZIKV) in a subject in need thereof, the array comprising:
- a base portion;
- and
- a plurality of microneedles extending from the base portion and containing an immunogen, and optionally at least one adjuvant, wherein the immunogen comprises a fusion protein, wherein the fusion protein comprises a Zika virus (ZIKV) envelope protein, a signal peptide, and a multimerization domain, wherein:
- the signal peptide is a premembrane (prM) signal peptide, an IgG signal peptide, or a human secretory signal peptide hidden Markov model, and
- the multimerization domain is an immunoglobulin Fc domain, a T4 fibritin foldon trimerization domain, or a human collagen XV trimerization domain.
Dependencies are inferred from the claim text.