Deconvolution method
The present invention relates generally to novel applications in combating infectious disease, cancer, allergy and autoimmune diseases. In one aspect, the invention relates to identifying one or more protein binding moieties of interest. In another aspect, the present invention relates to identifying one or more candidate vaccines.
1. A method for identifying an antibody or antigen binding fragment thereof comprising the steps of:
(a) screening a library of antibodies or antigen binding fragments against at least one immunogen;
(b) obtaining a plurality of antibodies or antigen binding fragments that are specific for the immunogen;
(c) dividing the plurality of antibodies or antigen binding fragments into at least a first pool and a second pool, wherein each pool contains at least one antibody or antigen binding fragment;
(d) testing said antibodies or antigen binding fragments from said first pool for function in an vitro assay;
(e) dividing the antibodies or antigen binding fragments from said first pool into two or more sub-pools, to the extent function in an vitro assay is observed in step (d), wherein each sub-pool contains at least one antibody or antigen binding fragment;
(f) testing said antibodies or antigen binding fragments from said first and second sub-pools of said first pool for function in an vitro assay; and
(g) identifying at least one antibody or antigen binding fragment from step (f) that are functional in an vitro assay.
2. A method according to claim 1 , further comprising:
(h) testing said antibodies or antigen binding fragments from said second pool for function in an vitro assay;
(i) dividing the antibodies or antigen binding fragments from said second pool into two or more sub-pools, to the extent function in an vitro assay is observed in step (h), wherein each sub-pool contains at least one antibody or antigen binding fragment;
(j) testing said antibodies or antigen binding fragments from said first and second sub-pools of said second pool for function in an vitro assay efficacy against disease; and
(k) identifying at least one antibody or antigen binding fragment from step (j) that is functional in an vitro assay.
3. The method according to claim 1 , wherein the library of antibodies or antigen binding fragments used to screen against at least one immunogen comprises a phage display library displaying antibodies or antigen binding fragments thereof.
4. The method according to claim 1 , further comprising:
(h) combining the antibodies or antigen binding fragments identified as functional in an vitro assay;
(i) testing the combination of antibodies or antigen binding fragments for function in an vitro assay; and
(j) identifying a synergistic combination of antibodies or antigen binding fragments.
5. The method according to claim 4 , further comprising:
(k) combining a subset of the antibodies or antigen binding fragments identified as a synergistic combination, wherein the subset combination comprises at least one less antibody or antigen binding fragment than the synergistic combination;
(l) testing the subset combination of antibodies or antigen binding fragments for function in an vitro assay; and
(m) identifying the subset combination of antibodies or antigen binding fragments that maintains synergistic activity.
6. The method according to claim 1 , wherein step (a), the screening of a library of antibodies or antigen binding fragments comprises screening a library of antibodies or antigen binding fragments against a first and a second immunogen.
7. The method according to claim 6 , wherein step (b) of claim 1 , the obtaining a plurality of antibodies or antigen binding fragments that are specific for the immunogen, further comprises:
(ba) combining the plurality of antibodies or antigen binding fragments specific for the first immunogen with the plurality of antibodies or antigen binding fragments specific for the second immunogen;
(bb) testing the combination of pluralities of antibodies or antigen binding fragments for function in an vitro assay; and
(be) identifying a synergistic combination of pluralities of antibodies or antigen binding fragments functional in an vitro assay.
8. The method according to claim 7 , further comprising:
(bd) combining a subset of the pluralities of antibodies or antigen binding fragments identified as a synergistic combination, wherein the subset combination comprises at least one less antibody or antigen binding fragment than the synergistic combination;
(be) testing the subset combination of pluralities of antibodies or antigen binding fragments for function in an vitro assay; and
(bf) identifying the subset combination of pluralities of antibodies or antigen binding fragments that maintains synergistic activity.