Vanilla JS is great until you have to start using it in real life world. Here are some examples of what's really important when working on highly scalable web applications
Understnding customer needs
Issue investigations and gradual rollouts
Design decisions - cost vs revenue analysis
As you can see I have barely touched the actual JS framework to be used. While technical decisions do matter, pushing Vanilla JS because you are unable to fathom the breath of challenges faced by services like Twitter, just speaks about your shortcomings.
There is a reason Node.js has become popular for backend development instead of devs whipping out their own V8 based JS runtimes. There are more important shit to be dealth with. React will work just fine and spending inordinate amount of time deciding which frontend JS framework to use ends up becoming nothing more than bikeshedding.