Human antibodies to rift valley fever virus
The present disclosure is directed to antibodies binding to and neutralizing Rift Valley Fever Virus and methods for use thereof.
1 . A method of treating a subject infected with Rift Valley Fever Virus or reducing the likelihood of infection of a subject at risk of contracting Rift Valley Fever Virus, comprising delivering to said subject an antibody or antibody fragment comprising (i) heavy chain CDR1-3 comprising SEQ ID NO: 346, SEQ ID NO: 347 and SEQ ID NO: 348, respectively, and light chain CDR1-3 comprising SEQ ID NO: 592, SEQ ID NO: 593 and SEQ ID NO: 594, respectively; (ii) heavy chain CDR1-3 comprising SEQ ID NO: 424, SEQ ID NO: 425 and SEQ ID NO: 426, respectively, and light chain CDR1-3 comprising SEQ ID NO: 670, SEQ ID NO: 671 and SEQ ID NO: 672, respectively; or (iii) heavy chain CDR1-3 comprising SEQ ID NO: 532, SEQ ID NO: 533 and SEQ ID NO: 534, respectively, and light chain CDR1-3 comprising SEQ ID NO: 775, SEQ ID NO: 776 and SEQ ID NO: 777, respectively.
2 . The method of claim 1 , wherein said antibody or antibody fragment comprises heavy and light chain variable sequences comprising (i) SEQ ID NO: 176 and SEQ ID NO: 177, respectively; (ii) SEQ ID NO: 228 and SEQ ID NO: 229, respectively; or (iii) SEQ ID NO: 299 and SEQ ID NO: 300, respectively.
3 . The method of claim 1 , wherein said antibody or antibody fragment comprises heavy and light chain variable sequences having 70%, 80% or 90% identity to (i) SEQ ID NO: 176 and SEQ ID NO: 177, respectively; (ii) SEQ ID NO: 228 and SEQ ID NO: 229, respectively; or (iii) SEQ ID NO: 299 and SEQ ID NO: 300, respectively.
4 . The method of claim 1 , wherein said antibody or antibody fragment comprises heavy and light chain variable sequences having 95% identity to (i) SEQ ID NO: 176 and SEQ ID NO: 177, respectively; (ii) SEQ ID NO: 228 and SEQ ID NO: 229, respectively; or (iii) SEQ ID NO: 299 and SEQ ID NO: 300, respectively.
5 . The method of claim 1 , wherein said antibody is an IgG, or a recombinant IgG antibody or antibody fragment comprising an Fc portion mutated to eliminate or enhance FcR interactions, to increase half-life and/or increase therapeutic efficacy, or glycan modified to alter eliminate or enhance FcR interactions.
6 . The method of claim 1 , wherein said antibody or antibody fragment is administered after infection.
7 . The method of claim 1 , wherein said subject is a pregnant female, a sexually active female, or a female undergoing fertility treatments.
8 . The method of claim 1 , wherein delivering comprises antibody or antibody fragment administration, or genetic delivery with an RNA or DNA sequence or vector encoding the antibody or antibody fragment.
9 . The method of claim 1 , wherein the subject is a pregnant female and the method comprises protecting the health of a placenta and/or fetus of the pregnant a subject infected with or at risk of infection with Rift Valley Fever Virus.
10 . The method of claim 5 , wherein said mutated Fc portion is a LALA, LALA PG, N297, GASD/ALIE, DHS, YTE or LS mutation.
11 . The method of claim 5 , wherein said glycan modification is an enzymatic or chemical addition or removal of glycans or results from expression in a cell line engineered with a defined glycosylating pattern.