Heavy Chain and Domain Antibodies
The present invention related to heavy chain immunoglobulins or fragments thereof of the VHH or VNAR type, or domain antibodies (dAbs) of the heavy or light chains of immunoglobulins or fragments thereof, suitable for use in the management of infections, in particular gastrointestinal tract. The present invention also relates to a delivery system comprising these heavy chain immunoglobulins or functional fragments thereof of the VHH or VNAR type, or domain antibodies (dAbs) of the heavy or light chains of immunoglobulins or fragments thereof, and hosts comprising expression vectors encoding for these heavy chain immunoglobulins or functional fragments thereof of the VHH or VNAR type, or domain antibodies (dAbs) of the heavy or light chains of immunoglobulins or fragments thereof. The invention also related to food products and pharmaceutical preparations comprising the delivery system, and method for the preparation of food products according to the invention.
1 - 26 . (canceled)
27 . A heavy chain immunoglobulin fragment of the VHH type, having an amino acid sequence of at least 85% identity with SEQ ID NO: 1 and having affinity for rotavirus particle or antigen.
28 . A heavy chain immunoglobulin fragment according to claim 27 , wherein the heavy chain immunoglobulin or fragment thereof has an amino acid sequence of at least 90% identity with SEQ ID NO: 1.
29 . A heavy chain immunoglobulin fragment according to claim 28 , wherein the heavy chain immunoglobulin has the amino acid sequence of SEQ ID NO: 1.
30 . A heavy chain immunoglobulin fragment of the VHH-type, having an amino acid sequence selected from the group consisting of SEQ ID NOS: 2, 3, 4, 12, 14, 17, 19 and 20.
31 . A heavy chain immunoglobulin fragment according to claim 27 , wherein the heavy chain immunoglobulin fragment shows binding affinity for rotavirus with a dissociation constant of at least 10 exp 5.
32 . A heavy chain immunoglobulin fragment according to claim 27 , wherein the rotavirus strain is selected from the group consisting of Wa, CK5, Wa1, RRV and CK5.
33 . A heavy chain immunoglobulin or fragment thereof which binds the same epitope as the heavy chain immunoglobulin fragment of claim 29 .
34 . A multimeric molecule comprising a heavy chain immunoglobulin fragment of the VHH type according to claim 27 , in which VHH sequences are fused to yield multimeric units of 2 or more VHH units optionally linked via a spacer molecule.
35 . A multimeric molecule comprising two or more VHH sequences according to claim 27 , which are fused to yield 2, 3, 4 or 5 or more VHH units optionally linked via a spacer molecule.
36 . A multimeric molecule according to claim 34 , wherein the VHH having different specificities.
37 . A multimeric molecule according to claim 34 , wherein each of the VHH have affinity to any of the group consisting of rotavirus strains Wa, CK5, Wa1, RRV and CK5.
38 . A multimeric molecule according to claim 37 , wherein the VHH are combined as separate monomeric units or as combined units on a carrier.
39 . A method for the therapy or prophylaxis of rotaviral infection, comprising administering to a patient a heavy chain immunoglobulin or fragment thereof of claim 27 .
40 . A gene encoding a heavy chain immunoglobulin fragment of the VHH type according to claim 27 .
41 . An expression vector comprising the gene encoding the heavy chain immunoglobulin fragment according to claim 40 .
42 . An expression vector according to claim 41 wherein the expression vector comprises a constitutive promoter or a promoter suitable for GIT specific expression, preferably pldh.
43 . A micro-organism transformed with the expression vector of claim 41 .
44 . A micro-organism according to claim 43 wherein the micro-organism is Lactobacillus.
45 . A micro-organism according to claim 44 wherein the Lactobacillus is Lactobacillus casei.
46 . A multivalent immunoglobulin comprising a heavy chain immunoglobulin fragment according to claim 27 .
47 . A multivalent immunoglobulin according to claim 46 wherein the heavy chain immunoglobulin fragment comprises antigen binding sites derived from the same parent antibody or fragment thereof.
48 . A multivalent immunoglobulin according to claim 46 wherein the heavy chain immunoglobulin fragment comprises antigen binding sites derived from different antibodies which bind the same epitope.