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 comprising a gene encoding an N-terminally truncated form of the VSV surface glycoprotein G (VSV G) (G/Stem), wherein the gene 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.
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. 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.
6. 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.
7. The vector of claim 1 , wherein the stem region comprises 68, 42, or 16 amino acids.