Heavy chain and single domain antibodies
The present invention relates 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 of the 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 relates to food products and pharmaceutical preparations comprising the delivery system, and methods for the preparation of food products according to the invention.
1. A delivery system for delivering antibodies to the gastrointestinal tract comprising a probiotic lactic acid bacterium transformed with a gene encoding heavy chain immunoglobulins of the VHH type or fragments thereof derived from llama which neutralize rotavirus and have an amino acid sequence with at least 85% percent sequence identity to SEQ ID NO: 1, or comprise SEQ ID NO: 1, 2, 3, 4, 12, 14, 17, 19 and 20, wherein expression of the immunoglobulins or fragments thereof in the gastrointestinal tract following administration to a subject in need thereof inhibits rotavirus infection in the gut of the subject.
2. The delivery system as claimed in claim 1 wherein the delivery system is encapsulated in a capsule.
3. The delivery system of claim 1 wherein the pro-biotic lactic acid bacterium is Lactobacillus or Bifidobacterium.
4. The delivery system of claim 1 wherein the probiotic lactic acid bacterium is Lactobacillus casei.
5. The delivery system of claim 1 wherein the immunoglobulins of the VHH type or fragments thereof are expressed on the surface of the transformed probiotic lactic acid bacterium.
6. The delivery system of claim 1 , wherein the immunoglobulin of the VHH type has an amino acid sequence as set forth in SEQ ID NO: 1.
7. The delivery system of claim 1 , wherein the immunoglobulin of the VHH type has an amino acid sequence as set forth in SEQ ID NO: 2.
8. The delivery system of claim 1 , wherein the immunoglobulin of the VHH type has an amino acid sequence as set forth in SEQ ID NO: 3.
9. The delivery system of claim 1 , wherein the immunoglobulin of the VHH type has an amino acid sequence as set forth in SEQ ID NO: 4.
10. The delivery system of claim 1 , wherein the immunoglobulin of the VHH type has an amino acid sequence as set forth in SEQ ID NO: 12.
11. The delivery system of claim 1 , wherein the immunoglobulin of the VHH type has an amino acid sequence as set forth in SEQ ID NO: 14.
12. The delivery system of claim 1 , wherein the immunoglobulin of the VHH type has an amino acid sequence as set forth in SEQ ID NO: 17.
13. The delivery system of claim 1 , wherein the immunoglobulin of the VHH type has an amino acid sequence as set forth in SEQ ID NO: 19.
14. The delivery system of claim 1 , wherein the immunoglobulin of the VHH type has an amino acid sequence as set forth in SEQ ID NO: 20.
15. The delivery system of claim 1 , wherein the immunoglobulin of the VHH type has an amino acid sequence with at least 95% percent sequence identity to SEQ ID NO: 1.
16. A method for delivering antibodies to the gut in the treatment of rotavirus infections using a micro-organism transformed with the gene encoding for heavy chains immunoglobulins of the VHH type or fragments thereof, comprising administering the delivery system of claim 1 to the gut of the human or animal in need of therapy such that the heavy chain immunoglobulins of the VHH type, or fragments thereof, are expressed and/or secreted in the gut.
17. The method of claim 16 wherein the heavy chain immunoglobulin or fragments thereof of the VHH type are specific to rotavirus.