Recombinant viral vectors
The present relation relates to recombinant vesicular stomatitis virus for use as prophylactic and therapeutic vaccines for infectious diseases of AIDS. The present invention encompasses the preparation and purification of immunogenic compositions which are formulated into the vaccines of the present invention.
1. A recombinant vesicular stomatitis virus (VSV) vector wherein the gene encoding the VSV surface glycoprotein G (VSV G) comprises a polynucleotide encoding a polypeptide comprising:
a transmembrane domain;
a cytoplasmic tail; and
an ectodomain comprising a stem region,
wherein the ectodomain, and not the transmembrane domain, comprises one or more HIV Env gp41 membrane-proximal external region (MPER) epitopes,
and wherein the stem region comprises the amino acid sequence of one or more of SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 8, SEQ ID NO: 11 and SEQ ID NO: 12.
2. The vector of claim 1 wherein the HIV Env Epitope is recognized by antibodies PG9, PG16, 2G12, b12, 2F5, 4E10 or Z13, or other Env-specific antibodies, including broad potent neutralizing trimer-specific antibodies.
3. A vaccine comprising the vector of claim 1 .
4. The vaccine of claim 3 , wherein the vaccine is an intramuscular or mucosal vaccine.
5. A method of producing an immune response or eliciting an immune response against HIV comprising administering to a mammal the VSV vector of claim 1 .
6. The method of claim 5 , wherein the HIV Env Epitope is recognized by a PG9, PG16, 2G12, b12, F15, 4E10, Z13 or a broadly neutralizing trimer-specific antibody.
7. The method of claim 5 , wherein the vector is administered to a nasal and/or oral cavity.
8. The method of claim 5 , wherein the vector is administered over a vaccine schedule from about 0 to 8 weeks.
9. The vector of claim 1 , wherein the stem region comprises the amino acid sequence of one or more of SEQ ID NO: 3, SEQ ID NO: 4, and SEQ ID NO: 9.
10. The vector of claim 1 , wherein the stem region comprises the amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 8, SEQ ID NO: 11, or SEQ ID NO: 12.
11. The vector of claim 1 , wherein the stem region comprises 68, 42, or 16 amino acids.