HI @mantana ,
A good question for a complicated issue - why does vaccination work to protect from infection when different HBsAg species are present in the virus which is shed by an infected person?
As we have discussed elsewhere in the forum (see here), HBV infection in any one person is actually a pool of HBV genome variants (which I previously termed quasispecies). Actually, John Tavis and I have chatted about this offline and we agree that this term is not correct (even though used widely in the literature) since these genome variants do not contain mutations which are linked to each other (so behaving like genetically conserved species) but are instead generated randomly and enriched from selection pressure by the immune system or some antiviral therapies.
So over the course of HBV infection, the prevalence of genome variants (and the HBsAg variants they generate) evolves according to the immune selection pressure from the infected person’s immune system. Fortunately, MOST of these variants will still be recognized by antibodies produced from standard vaccination. So vaccination still effectively prevents the development of infection from this viral innoculum.
Now in a person with already established infection, the pool of immune escape HBsAg is already well entrenched and can evade the vaccine response. This is why therapeutic vaccination has failed to date in all clinical trials to achieve functional cure (despite the production of strong vaccine responses).
This is different from the situation with SARS CoV2 (and influenza) where the entire viral innoculum can be entirely immune escape against a particular vaccine.
Best regards,