Internal microstructure of spray dried particles affects viral vector activity in dry vaccines

•The internal microstructure of dried particles varies with excipients.•Viral activity decreased as the total (internal + external) solid-air interfacial area increased.•The viral vector analogue is predominantly located at or near the solid-air interfaces.•Surface area within spray dried particles is an indicator of activity.•Internal voids can mask the effects of operating conditions and excipient selection.