Sirna plus nanovaccine possible combination

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Just wondering what all the experts here think about this.

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Hi @Mike2,

Thanks for sharing this study. This has been carried out in a relatively artificial mouse model. It’s a great start, but it will be important to know if it works under more physiologically accurate conditions.

Thomas

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Dear @Mike2,

The approach of combining a therapeutic vaccine and siRNA has already been tried in humans and has failed to produce even a single case of functional cure. Moreover, adding a therapeutic vaccine to siRNA has no additive effects on HBsAg reduction compared to siRNA alone, even though large amounts of anti-HBs are produced. Additionally, many therapeutic vaccines have been tried in the clinic and have failed to achieve any effects on HBsAg levels in clinical studies.

As Thomas has mentioned, the mouse model employed here has important deficiencies:

  1. HBsAg levels are much lower than in human infection. This is important since HBsAg interferes with the vaccine response.
  2. In human infection, there is enormous genetic diversity in HBV infection leading to the evolution of numerous immune (vaccine) escape variants of HBsAg. This diversity is absent in this mouse model.
  3. The vaccine used in this study uses an adjuvant that stimulates TLR9 (CpG). This adjuvant has different effects in humans than in mice. Its not clear from this study what the nature of the synergy is between the siRNA and vaccine used. It does not appear to be from the production of anti-HBs from the vaccine itself.

Patients should really ignore pre-clinical data from mouse models. Except for older generation approved therapies (NUCs), these models have failed to predict clinical efficacy with any of the current antivirals for HBV still in development.

@availlant

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hi thomas my first time on this website idk how to make a post myself can only comment for now,

I’ve been on pills for almost 3 years now I still have 157 load of virus left and lately ultrasound doctor commented “ the previously seen left simple hepatic cyst and the hyperexhonic areas seen in the right hepatic lobe remain stable and unchanged there’s no signs of focal lesions”

Should I be worried about the hepatic cyst? I’m not so sure about how damaging it can be please help me if you have knowledge about this

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Hi @Uklife,
Welcome to the community and @ThomasTu will get back to you soon. But I don’t think this result is a sign of concern. It shows that the previously identified cyst remains the same, has not changed, and there is no evidence of lesions. I do have multiple cysts on my liver as well and we have been monitoring them with a 6-month ultrasound. It does not seem that these cysts are causing further issues, but continued monitoring is crucial. I hope this helps. Best, Bansah1

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Dear @Uklife,

The older we get, the more likely we are to have hepatic cysts. Their presence is not caused by nor has anything to do with HBV. They are typically benign.

@availlant

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Hi @Uklife,

Indeed, I join @Bansah1 in welcoming you to the forum. Great question and well answered by @Bansah1 and @availlant. Cysts are considered benign and many people live with them without ever knowing that they are there: ~5% of people have them (whether they have hep B or not).

Hope this helps,
Thomas

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Thanks a lot guys! And I love this community already @Bansah1 @availlant

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Hi @Uklife,
You are welcome and I am glad to hear that you are loving the community. That is why we are here. Thank you, Bansah1.

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