Anti-dengue virus antibodies having cross-reactivity to zika virus and methods of use
The disclosure provides anti-DENV antibodies having a cross-reactivity to ZIKV and methods of making and using the same. The anti-DENV antibodies have uses that include treating or preventing ZIKV infection.
1 . A method for treating or preventing Dengue virus infection, comprising administering an antibody that binds to Zika virus, wherein the antibody comprises:
(a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 12, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 15, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 20, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 21, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 24 and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 27.
2 . The method of claim 1 , wherein the antibody further comprises a polypeptide, wherein the polypeptide comprises a variant Fc region comprising at least one amino acid alteration in a parent Fc region, wherein the variant Fc region has a substantially decreased Fc γ R-binding activity and does not have a substantially decreased C1q-binding activity when compared to the parent Fc region, wherein the variant Fc region comprises Ala at position 234, Ala at position 235 and further comprises any one of the following amino acids (a) to (c):
(a) Glu at position 267, Phe at position 268, and Thr at position 324;
(b) Ala at position 236, Glu at position 267, Phe at position 268, Thr at position 324, and Glu at position 332; and
(c) Ala, Glu, Met, or Trp at position 326 and Ser at position 333;
wherein the positions are according to EU numbering.
3 . The method of claim 2 , wherein the variant Fc region further comprises amino acids selected from the group consisting of:
(a) Ala at position 434;
(b) Ala at position 434, Thr at position 436, Arg at position 438, and Glu at position 440;
(c) Leu at position 428, Ala at position 434, Thr at position 436, Arg at position 438, and Glu at position 440; and
(d) Leu at position 428, Ala at position 434, Arg at position 438, and Glu at position 440;
wherein the positions are according to EU numbering.
4 . The method of claim 2 , wherein the polypeptide comprises the amino acid sequence of any one of SEQ ID NOs: 51-54 and 56-59.
5 . The method of claim 1 , wherein the antibody comprises
(a) a VH sequence selected from the group consisting of: 3CH1047 (SEQ ID NO: 6), and 3CH1049 (SEQ ID NO: 95) with a human IgG1 CH sequence selected from the group consisting of: SG182 (SEQ ID NO: 46), SG1095 (SEQ ID NO: 54) and SG1106 (SEQ ID NO: 59); and
(b) a VL sequence selected from the group consisting of 3CL (SEQ ID NO: 7) and 3CL633 (SEQ ID NO: 98), with a human CL sequence SK1 (SEQ ID NO: 60).