By 'mainstream', I mean that Vtubers like in Japan would be on the morning talk shows, be featured in advertisements on TV, have shows about V-Tubers on TV (there is a light novel with an anime adaptation called VTuber Legend: How I Went Viral After Forgetting to Turn Off My Stream), collaborations with V-Tubers and sports teams are a common occurrence, and while we have had some of these things in the West, it's not as pervasive as it is in Japan.
In my opinion with Western media being continually ass, it's only a matter of time.
You would have to wait many years before it truly became mainstream. All the Old People currently running various mainstream media companies wouldn't know how to approach it outside of throwing some random intern at it to "make it work." Western culture is still too heavily focused on regular Hollywood celebrities and various TV personalities to shift over to VTubers any time soon, and with luck it never will.
The cross-contamination would be lethal, and we'd see a drastic infection of VTubing by MSM corporations as they tried to take over the industry completely and funnel everyone into their advertiser-safe brands and celebrity-lookalike characters. I think that would be the first attempt; make them look like people you already know.
Anime is everywhere in Japan, but not in the US. I think the transition would simply be too jarring for most people in the general population, who remain irrevocably normies.