Aa
replicor
So what was the outcome of Replicor..Any results?
As can be seen by looking at the OTS presentation from last fall, recently presented here also, the patients had all high , some very very high, hbsag levels.
It can be assumed, that patients that have spontaneously low hbsag levels, likely as a results of a fortunate constellation of epitopes, T cell clones and cytokine milieu, will respond better and more stable to the additional artificial lowering of the hbsag that the treatment provides.
It is a big difference if hbsag is low as a symptom of improving Tcell immunity or is pushed down by interfering RNA or the replicor compound ( much much lower however). Failure to see that clearly is the reason for all these IMO naive predictions like for arrowhead etc, that the lowering by blockade will typically lead to a spontaneous self stabilization of the infection status.
Replicors trials have made that painfully clear.
Immune stimulation in addition to hbsag lowering works much better, but the correct epitopes are still needed ( Not just activated T and B cells) and the cells with integrated full genomes can also lead to a respreading of the virus after therapy has ended, even if this might take a long time.
a key problem is, that even a high titer anti hbsag antibody is not long term sufficient to keep the regrowth of the virus completely in check. Its reinfection blocking effect is never perfect on a microscopic local scale in the liver. Growing clusters of reinfected cells need to be destroyed from time to time by a localized T cell attack, that responds to the growing of this cluster.
While the inside forces of Tcell immunity will be helped by lowering hbsag, a tolerizing agent with some unspecific immune blocking activity in addition, epitope availability and intactness are still critical to switch on the permanent inside t cell maintenance "therapy" that is the heart of the "cure' in chronic HBV.
It can be assumed, that patients that have spontaneously low hbsag levels, likely as a results of a fortunate constellation of epitopes, T cell clones and cytokine milieu, will respond better and more stable to the additional artificial lowering of the hbsag that the treatment provides.
It is a big difference if hbsag is low as a symptom of improving Tcell immunity or is pushed down by interfering RNA or the replicor compound ( much much lower however). Failure to see that clearly is the reason for all these IMO naive predictions like for arrowhead etc, that the lowering by blockade will typically lead to a spontaneous self stabilization of the infection status.
Replicors trials have made that painfully clear.
Immune stimulation in addition to hbsag lowering works much better, but the correct epitopes are still needed ( Not just activated T and B cells) and the cells with integrated full genomes can also lead to a respreading of the virus after therapy has ended, even if this might take a long time.
a key problem is, that even a high titer anti hbsag antibody is not long term sufficient to keep the regrowth of the virus completely in check. Its reinfection blocking effect is never perfect on a microscopic local scale in the liver. Growing clusters of reinfected cells need to be destroyed from time to time by a localized T cell attack, that responds to the growing of this cluster.
While the inside forces of Tcell immunity will be helped by lowering hbsag, a tolerizing agent with some unspecific immune blocking activity in addition, epitope availability and intactness are still critical to switch on the permanent inside t cell maintenance "therapy" that is the heart of the "cure' in chronic HBV.
Your explanation about the difference in release mechanism for HBV and HDV virions is fascinating. I think it is unexpected result, even for Replicor.
what about the patients with low hbsag less than 1000iu/ml naturally or by peginterferon/longterm nucs treatments.
is there any data on replicor for these cases where some immune control over hbv is already weakly present?
i guess these cases are much easier to reach svr and high hbsab
is there any data on replicor for these cases where some immune control over hbv is already weakly present?
i guess these cases are much easier to reach svr and high hbsab
For good and valid reasons, like the size and protein composition of HDV virions vs hbv virions, hdv is presumed to be treated like a surface antigen particle in the formation and release pathway. HBV virion morphogenesis and secretion is different and not directly controlled by the replicor compounds. Additionally, The almost perfect parallelism in hbsag and hdv serum reduction, much much more profound than hbv vl reductions, lends strong support to this theory.
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