If employment is at-will, the company has the right to change most policies at any time. Employees are expected to follow the policies of the company as long as they are legal. While it is best practice to have signed acknowledgement forms for handbooks in each employee's file, it is not required to enforce those policies.
However, if an employee has been given multiple chances to return the acknowledgement form and/or to discuss concerns, they are still expected to follow the updated handbook. You should document in writing that the employee is expected to follow all policies of the company including those in the new handbook and their failure to return the acknowledgement does not change that requirement. Then put that document and any response into their employee file.
The Workplace Advisors is BSCAI's endorsed HR partner, providing HR support, recruiting and employee engagement services. For a link to our menu of services for BSCAI members, go to www.TheWorkplaceAdvisors.com/BSCAI