Compositions and methods for inhibiting pathogen infection
The presently-disclosed subject matter relates to antibodies, compositions, and methods for inhibiting and treating virus infection in the respiratory tract and virus transmission through the respiratory tract. In particular, the presently-disclosed subject matter relates to inhibiting and treating virus infection in a subject using compositions and antibodies that trap viruses in mucus of the respiratory tract, thereby inhibiting transport of virus across or through mucus secretions.
1. A method for treating, immobilizing or inhibiting a viral infection by a virion in a subject in need thereof, the method comprising administering to the subject, via an inhaled route, a recombinant antibody with a specific affinity for the virion, the recombinant antibody comprising a human or humanized Fc region, wherein the recombinant antibody comprises a population of antibodies in which at least 40% comprise an oligosaccharide having a G0 glycosylation pattern comprising a biantennary core glycan structure of Manα1-6(Manα1-3)Manβ1-4GlcNAcβ1-4GlcNAcβ1 with terminal N-acetylglucosamine on each branch that enhances the trapping potency of the recombinant antibody in mucus, so that the recombinant antibody binds to the virion to form an antibody/virion complex that is trapped in the subject's mucus.
2. The method of claim 1 , wherein the recombinant antibody comprises an N-linked glycosylation site on the Fc region of the antibodies to which the oligosaccharide is attached.
3. The method of claim 1 , wherein 50% or more of the recombinant antibodies in the population have a glycosylation pattern comprising the biantennary core glycan structure Manα1-6(Manα1-3)Manβ1-4GlcNAcβ1-4GlcNAcβ1 with terminal N-acetylglucosamine on each branch.
4. The method of claim 1 , wherein the recombinant antibody is configured to bind to a non-neutralizing epitope of the virion.
5. The method of claim 1 , wherein administering comprises administering a dose at a sub-neutralization dose level.
6. The method of claim 1 , further comprising reducing the mobility of the virion in the patient's mucus to no more than about 50% relative to its mobility in water.
7. The method of claim 1 , further comprising reducing the percentage of virion that can penetrate the patient's mucus by at least 10%.
8. The method of claim 1 , wherein the recombinant antibody is a human or humanized IgG or IgM monoclonal antibody, or a fragment or derivative thereof.
9. The method of claim 1 , wherein the recombinant antibody is formulated as an aerosol composition.
10. The method claim 1 , wherein the virion is selected from: respiratory syncytial virus (RSV), influenza virus, adenovirus, human rhinovirus, coronavirus, and parainfluenza virus.
11. The method claim 1 , wherein the virion is respiratory syncytial virus.
12. A method of immobilizing a respiratory virion in mucus of a subject's lung, the method comprising administering to the subject, via an inhaled route, a population of recombinant antibodies with a specific affinity for the virion, the recombinant antibodies comprising a human or humanized Fc region, wherein at least 50% of the recombinant antibodies comprise an oligosaccharide having a glycosylation pattern comprising the biantennary core glycan structure Manα1-6(Manα1-3)Manβ1-4GlcNAcβ1-4GlcNAcβ1 with terminal N-acetylglucosamine on each branch to enhance the trapping potency of the recombinant antibody in mucus, so that the recombinant antibodies bind to the virion to form an antibody/virion complex that is trapped in the subject's mucus.
13. The method of claim 12 , wherein the recombinant antibodies are configured to bind to a non-neutralizing epitope of the virion.
14. The method of claim 12 , wherein administering comprises administering a dose at a sub-neutralization dose level.
15. The method of claim 12 , wherein the recombinant antibodies comprise an N-linked glycosylation site on the Fe region of the antibodies to which the oligosaccharide is attached.
16. The method of claim 12 , further comprising reducing the mobility of the virion to no more than about 50% relative to its mobility in water.
17. The method of claim 12 , further comprising reducing the percentage of virion that can penetrate mucus by at least 10%.
18. The method of claim 12 , wherein the recombinant antibody is a human or humanized IgG or IgM monoclonal antibody, or a fragment or derivative thereof.
19. The method of claim 12 , wherein the recombinant antibody is formulated as an aerosol composition.
20. The method of claim 12 , wherein at least 60% of the recombinant antibodies in the population have a glycosylation pattern comprising the biantennary core glycan structure Manα1-6(Manα1-3)Manβ1-4GlcNAcβ1-4GlcNAcβ1 with terminal N-acetylglucosamine on each branch.
21. The method of claim 12 , wherein the virion is selected from: respiratory syncytial virus (RSV), influenza virus, adenovirus, human rhinovirus, coronavirus, and parainfluenza virus.
22. The method claim 12 , wherein the virion is respiratory syncytial virus.
23. A method for inhibiting a respiratory virion in mucus of a subject's lung, the method comprising immobilizing the virion by administering to the subject, via an inhaled route, a population of recombinant antibody in which at least 40% comprise an oligosaccharide having a G0 glycosylation pattern comprising a biantennary core glycan structure of Manα1-6(Manα1-3)Manα1-4GlcNAcβ1-4GlcNAcβ1 with terminal N-acetylglucosamine on each branch, wherein the recombinant antibody has a specific affinity for the virion so that the recombinant antibody is trapped in the subject's mucus, the recombinant antibody comprising a human or humanized Fc region, wherein the recombinant antibody comprises an oligosaccharide having a glycosylation pattern that enhances the trapping potency of the recombinant antibody in mucus.