Is Cure coming in future?

Hi doctor @ThomasTu ,

I saw you on YouTube that you are participating in clinical trails for cure hepatitis b.

I saw some trails going to made for hepatitis b cure.
When is nasvac therapeutic vaccine is going to be released?
How many phases of clinical trails will be there?
Why is thervacb show so much promising on curing hepatitis b?
Is that mouse model is successful in any previous trails of other therapeutic vaccines?

I’m like the most people who live with hope…

Dear Helpme786,

I’m a senior HBV virologist and director of a local drug discovery institute. Your questions about a cure coming are very good. The good news is that there are an enormous number of drug and vaccine strategies being tried in Universities, small biotechnology companies, and major pharmaceutical companies. I am personally confident that major improvements in therapy for HBV will arrive within 5 years, or perhaps a bit longer. However, please remember that this is just my personal opinion, and that it is impossible to predict the pace of scientific and medical advances. We are working at the edge of the unknown, and the complexity of the problem is truly daunting.

As to your specific questions:

  1. The international standard for clinical study design is in 3 phases. Phase I is in small numbers of healthy folks and tests safety and potential dose ranges for the new therapy. Phase II is a larger study to further look at safety and to identify the dose that should be used therapeutically. Phase III is a large study that looks at safety and how well the therapy works. In some cases, the phases can be integrated together, but in all cases all 3 major sets of questions need to be studied.

  2. ThervacB is showing such promise because it takes advantage of decades of study of the immune system and understanding of HBV biology. It looks great in animals, and I really hope that plays out in the clinical trials. Pretty much all of the prior therapeutic vaccine trials in the animals were only moderately or not promising, but each one contributed more understanding that helped guide design of the next one.

  3. The nasvac vaccine also takes advantage of advances in understanding of HBV and immunology. It appears to be working in some people in the early trial data reported. Short-term drops in HBsAg were modest, but the immune response against HBV appears to be on the “slow but steady” path, with some patients achieving functional cure at later times. Note that this trial data is from a small number of people, and so larger studies are needed. However, it looks like they may be onto something!

I hope this helps.

John.

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Thank you so much for a breif explanation sir, I hope everything will be settled in future. Soany like me don’t know how they get this virus untill they went for operation or some medical blood checkups. I’m an engineering student and I never did sex or blood transfusion before. Doctors thought I may got this through RMP doctors while giving injection for normal viral fever… But now I’m an victim… I’m strong and having high spirits. I never dispointed…

My last question : under taking medications can I live my normal life and going to my job… I’m working in a small software company in night shifts.

Question 2 : can you please clearly explain how can I stop transmitting to my wife after marriage in future… Can I make a normal sex after she got vaccinated… Or still do I need to use condoms.

Thank you doctor

Dear @Helpme786,

Thanks for your questions and thanks @john.tavis for your informative answers.

  1. You can definitely live and work normally. The only thing is remaining under monitoring (visiting a doctor and blood tests every 6 months) and taking your pill each day. Otherwise, the majority of us with hep B are living like everyone else.

  2. As long as your wife’s anti-HBs antibody levels are high enough (you can check this with a blood test, the threshold is 10mIU/mL), she will be protected.

Thomas

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hi @john.tavis & @ThomasTu ,

Today i came with new question :slightly_smiling_face:.

1)what is RNAi gene silencer and TLR-8 agonist mechanisms?
2)could you please tell me about the results of VIR-2218 & Selgantolimod (GS9688) in phase 2?
3) please comment on these combinations 1)VIR-2218 and VIR-3434, 2)VIR-2218 and Selgantolimod
(GS9688).

Dear Helpmegod,

An RNA silencer is a drug made from a small piece of RNA (kind of like a DNA) that has been modified to make it more stable and be able to get into cells. They bind to a bigger type of RNA in cells called mRNAs and block mRNA function. That stops production of the viral proteins from the mRNA, blocking viral function.

TLR8 is a “pathogen associated molecular pattern” detector that detects foreign RNA once it gets into the cells (in a part of the uptake pathway called “endosomes”). It normally detects RNA from a pathogen and then triggers the immune system to fight the pathogen. An “agonist” is a molecule that binds to something and turns it on (vs. an “antagonist” that binds to something and turns it off). A TLR8 agonist is therefore a drug that binds to TLR8, turns it on, and triggers the immune response to attack HBV.

In a completely irrelevant but interesting note, TLR stands for “Toll Like Receptor”. TLRs are named after a German word that can be translated as “Cool!”. This is because the first member of the class was identified in studies with mutant fruit flies that looked interesting under a dissecting microscope. The researchers were German, and the lab director looked through the ‘scope and said “Cool!”.

VIR-2218 is an siRNA drug in phase II trials.

Selgantolimod is a TLR8 agonist in Phase II trials.

Combining an siRNA and a TLR8 agonist together in a combination therapy makes sense scientifically. The TLR8 agonist would help turn on the immune system, and the siRNA would help suppress viral replication and reduce the amount of HBV proteins in cells. That is important because some of the viral proteins partially block the immune system. Overall, this strategy focuses on ramping up the immune system to kill HBV infected cells. The risks with this strategy are that if the immune response becomes too vigorous a patient may get ill from killing too many HBV+ cells too fast. However, that does not seem to be very likely to happen as the problem with most siRNAs and the TLR8 drugs when given by themselves is that they did not attack the virus as hard as we had hoped (they worked, just not spectacularly). However, only clinical trials can really find out if a combination works in people.

Note that this is only one of the very many logical drug combinations being considered now.

John Tavis

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