Hi Amanda-
If you have a different From versus Reply-To email address can cause a higher chance of being classified as spam or untrusted sender.
An option that you could exercise is a shared aliased mailbox - we use a few shared mailboxes that have multiple people accessing to deal with OOO replies since we do have a handful of direct replies....by sharing the responsibility, we can deal with OOO, true replies, reply-to unsubscribes (even though we have the opt-out link) and even some questions that they want to send to sales or customer support.
Hope this helps!