The Signature program caches a lot of data in order to speed up the processing of emails.
Sometime when you create a new signature configuration or create new groups in the Domino Directory the changes won't take effect until the server is restarted or the cache is refreshed.
To avoid a server restart you can use the action in the esig database Send cache email.
The action is under the Action Menu and is called Send cache email.
The cache will be immediately refreshed and the changes you have made should now be working.
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CMS DOM v4