The issue occurs when the sender has another third-party antispam solution that prevents HES to send the email to the final recipient.
To resolve the issue, configure the third-party antispam solution and safelist the HES IP addresses. For more information, refer to the following KB article: Accepting emails coming only from Hosted Email Security (HES) server.
The error is also generated if the Content Filtering in Microsoft Exchange. For more information, refer to the following Microsoft topic: 550 5.7.1 Message rejected as spam by Content Filtering.