Prefusion-stabilized cmv gb proteins
AssigneeBoard of Regents, The University of Texas System
InventorsJason MCLELLAN, Madeline SPONHOLTZ, Patrick BYRNE, Ching-Lin HSIEH, Ling ZHOU, Ryan MCCOOL, Nicole JOHNSON, Jory GOLDSMITH, Ajit RAMAMOHAN
Life of this patent
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Abstract
Provided herein are engineered hCMV gB polypeptides. In some aspects, the engineered gB polypeptides exhibit enhanced conformational stability and/or antigenicity. Methods are also provided for use of the engineered gB polypeptides as diagnostics, in screening platforms, and/or in vaccine compositions.
Claims34
(canceled)
An engineered human cytomegalovirus (HCMV) gB protein ectodomain comprising a sequence having at least 90% identity to amino acids 23-704 of SEQ ID NO:
- 1, said engineered protein comprising at least one substitution or set of substitutions selected from the group consisting of:
- Y89C/N599C;
- Y89C/G622C;
- V93C/V552C;
- V93C/L603C;
- A97C/R540C;
- A97C/A549C;
- G99C/L616C;
- R104C/I642C;
- R104C/T644C;
- E106C/T644C;
- L121C/N496C;
- M126C/W431C;
- V128C/V429C;
- V134C/I653C;
- A135C/I653C;
- Y153C/Y160C;
- Y153C/Y242C;
- Y160C/Y708C;
- N220C/E657C;
- T221C/T553C;
- H222C/E657C;
- K260C/S641C;
- V273C/L616C;
- T347C/A650C;
- I356C/A500C;
- M371C/A505C;
- Y415C/G433C;
- Y415C/K435C;
- F421C/V429C;
- G543C/K617C;
- G543C/F619C;
- D544C/Q597C;
- D544C/I620C;
- V545C/I618C;
- G604C/Y667C;
- Q612C/R662C;
- T644C/S647C;
- F661C/Y218C;
- S674C/E698C;
- D679C/R685C;
- D679C/E686C;
- E698C/R673C;
- N750C/G753C;
- L102W;
- I103Y;
- T112L;
- T112Y;
- V127F;
- K130W;
- K130Y;
- K130L;
- T159W;
- L162W;
- S223V/T253V/T270M/T659V;
- T253L;
- K260W;
- A267M;
- T270W;
- V273F;
- R354W;
- I356F;
- S367M;
- A396V;
- G433H;
- A500M;
- A500L/A503S;
- F541W;
- N556Y;
- E597F;
- E597Y;
- N599Y;
- R607Y;
- S641F;
- V645L;
- L616W;
- I620F;
- E627F;
- S643W;
- D646W;
- S647L;
- R662W;
- L664F;
- D679V/E682N;
- R685L/R607M;
- E686M;
- E686L/K691M;
- S689Y;
- G711L;
- L715F;
- L715F/V741Y/N750W;
- G731M;
- A738M;
- V741Y;
- I103R;
- V110E;
- D120R;
- Y153R/Y712E;
- Y155E;
- Y155E/G735K;
- Y155E/L709K;
- Y168E;
- Y218D/F584K;
- W240R;
- W240R/A732E;
- L241R/V728E;
- Y242D/L715K;
- V273K;
- I305E;
- R354E;
- E359R;
- R497E;
- Q501E;
- S526K;
- Y592E;
- N605E;
- H606E;
- L613D;
- P614R;
- D630R;
- M648E;
- A650D;
- I653D;
- D654E;
- L656D;
- V702E;
- K710E;
- V733D/F752K;
- K749E;
- N750K;
- E119P;
- 1121P;
- D122P;
- Y129P;
- A373P;
- A257P;
- K340P;
- N341P;
- A351P;
- G426P;
- L427P;
- H477P;
- V645P;
- A650P;
- L651P;
- E671P;
- L672P;
- I683P;
- M684P;
- E686P;
- K691P;
- G720P/A721P/A722P;
- A725P/V726P/A727P;
- Q98L/N658I;
- T100L/A267I;
- R104I;
- Y153F;
- L161E;
- L161R;
- L161W;
- E167I;
- F198W;
- T245E;
- T253L/T270L;
- D272N;
- A373F;
- D509L;
- D509R;
- R511Q;
- R512Q;
- R512W;
- S641E;
- T659V/N220F;
- E686N;
- R693L;
- R693L/K700V;
- and K700V, wherein the position are relative to SEQ ID NO:
- 1.
5-9. (canceled)
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17-19. (canceled)
23-24. (canceled)
26-27. (canceled)
30-34. (canceled)
36-38. (canceled)
40-42. (canceled)
44-46. (canceled)
48-52. (canceled)
54-57. (canceled)
59-66. (canceled)
Dependencies are inferred from the claim text.