HPV VACCINES
Provided herein are genetically modified arenaviruses suitable as vaccines against neoplastic diseases or cancer. The invention also relates to pharmaceutical compositions and methods for the prevention or treatment of certain infections causing neoplastic diseases or cancer, such as infections with oncogenic viruses. Specifically, provided herein are pharmaceutical compositions, vaccines, and methods of preventing or treating diseases and conditions caused by and associated with infections with Human Papillomavirus (HPV), such as cervical cancer, anogenital cancer, head and neck cancer and skin cancers. Also provided herein are immunotherapies for the treatment of a neoplastic disease, such as a neoplastic disease caused by infection with oncogenic viruses.
1 . An infectious, replication-deficient arenavirus viral vector comprising a first nucleotide sequence encoding an antigen of an oncogenic virus, or an antigen of a tumor-associated virus, wherein the oncogenic virus or tumor-associated virus is not cytomegalo virus, Hepatitis B virus, or Hepatitis C virus.
2 .- 63 . (canceled)
64 . A method of treating or preventing a human papillomavirus infection in a patient, wherein said method comprises administering to the patient a viral vector of claim 1 .
65 .- 89 . (canceled)
90 . An arenavirus genomic segment, wherein the genomic segment is engineered to carry a viral ORF in a position other than the wild-type position of the ORF and a first nucleotide sequence encoding a polypeptide comprising an amino acid sequence that is at least 99% identical to SEQ ID NO:10, and wherein the arenavirus genomic segment is selected from the group consisting of:
a. an S segment, wherein the ORF encoding the NP is under control of an arenavirus 5′ UTR;
b. an S segment, wherein the ORF encoding the Z protein is under control of an arenavirus 5′ UTR;
c. an S segment, wherein the ORF encoding the L protein is under control of an arenavirus 5′ UTR;
d. an S segment, wherein the ORF encoding the GP is under control of an arenavirus 3′ UTR;
e. an S segment, wherein the ORF encoding the L protein is under control of an arenavirus 3′ UTR; and
f. an S segment, wherein the ORF encoding the Z protein is under control of an arenavirus 3′ UTR.
91 . The arenavirus genomic segment of claim 90 , wherein the arenavirus 3′ UTR is the 3′ UTR of the arenavirus S segment, and wherein the arenavirus 5′ UTR is the 5′ UTR of the arenavirus S segment.
92 .- 131 . (canceled)
132 . The arenavirus genomic segment of claim 90 , wherein the arenavirus genomic segment is derived from lymphocytic choriomeningitis virus (“LCMV”), Pichinde virus, or Junin virus.
133 . The arenavirus genomic segment of claim 0132 , wherein the arenavirus genomic segment is derived from LCMV.
134 . The arenavirus genomic segment of claim 0133 , wherein the LCMV is MP strain, Armstrong strain, or Armstrong Clone 13 strain.
135 . (canceled)
136 . (canceled)
137 . A cDNA encoding the arenavirus genomic segment of claim 90 .
138 . A DNA expression vector comprising the cDNA of claim 137 .
139 . A host cell comprising the arenavirus genomic segment of claim 90 .
140 .- 273 . (canceled)
274 . A method of inducing an immune response in a subject wherein said method comprises administering to the patient a first infectious, replication-deficient arenavirus viral vector, and administering to the patient, after a period of time, a second, different infectious, replication-deficient arenavirus viral vector.
275 . The method of claim 274 , wherein the first arenavirus viral vector and the second arenavirus viral vector are derived from different arenaviruses.
276 . The method of claim 274 , wherein the first arenavirus viral vector is derived from Pichinde virus or Junin virus and the second arenavirus viral vector is derived from LCMV.
277 . The method of claim 276 , wherein the first arenavirus viral vector is derived from Pichinde virus.
278 . The method of claim 274 , wherein the first arenavirus viral vector is derived from LCMV and the second arenavirus viral vector is derived from Pichinde virus or Junin virus.
279 . The method of claim 274 , wherein the first arenavirus viral vector and the second arenavirus viral vector express the same antigen.
280 . The method of claim 274 , wherein the first arenavirus viral vector and the second arenavirus viral vector express different antigens.
281 . The method of claim 274 , wherein the first arenavirus viral vector and the second arenavirus viral vector each comprises a nucleotide sequence encoding a polypeptide that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, at least 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 10.
282 . A method of inducing an immune response in a subject wherein said method comprises administering to the patient a first infectious, replication-competent arenavirus viral vector, and administering to the patient, after a period of time, a second, different infectious, replication-competent arenavirus viral vector.
283 . The method of claim 282 , wherein the first arenavirus viral vector and the second arenavirus viral vector are derived from different arenaviruses.
284 . The method of claim 282 , wherein the first arenavirus viral vector is derived from Pichinde virus or Junin virus and the second arenavirus viral vector is derived from LCMV.
285 . The method of claim 284 , wherein the first arenavirus viral vector is derived from Pichinde virus.
286 . The method of claim 282 , wherein the first arenavirus viral vector is derived from LCMV and the second arenavirus viral vector is derived from Pichinde virus or Junin virus.
287 . The method of claim 282 , wherein the first arenavirus viral vector and the second arenavirus viral vector express the same antigen.
288 . The method of claim 282 , wherein the first arenavirus viral vector and the second arenavirus viral vector express different antigens.
289 . The method of claim 282 , wherein the first arenavirus viral vector and the second arenavirus viral vector each comprises a nucleotide sequence encoding a polypeptide that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, at least 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 10.