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    • Just a human being
      An example: Censorship in Science  Science Freedoom Institute a bare bone bastion of an organisation founded by Peter Gøtzsche in the ashes of the deathknell of the Cochrane Colaberation an organisation of which he was a foundational member.  An article by an Australian journalist, Maryanne Demasi, speaking out against censorship in media reporting and science. A MASSIVE systematic issue with potential negligent crimes against humanity.  “Science is facing a crisis of democracy. Now more than ever, vitriolic attacks are being leveled at people who debate opposing scientific views. Asking questions that challenge the establishment may be unsettling, but silencing debate and proclaiming that the “science is settled” is not the solution.”  “Belgian physician Jan Vandenbroucke once wrote, ‘Without the possibility of open debate, science simply ceases to exist.’” https://www.scientificfreedom.dk/2019/10/30/science-and-censorship-my-story/    
    • Just a human being
      While I was wanting to take a break from my posting here for the next month as you asked a question I answered. Unfortunately while I can post and publish I cannot discuss the matter further here as I am being censored. That’s science for you. Endemic censorship and dishonesty. 
    • MikeHerp
      The HSV cure research is partly funded by the NIH. So it’s unlikely that FHC would stop it. If they stopped it, they couldn’t get the funding anymore. The cutbacks, while unfortunate, only affect 5% of their staff. Like any other private institution, they aren’t immune to the effects of a crashed economy. Let's continue to provide support and remain patient. Good news will cone but we have to be ready for the occasional setback or delay.  I will communicate with them about the status at the next opportunity,
    • WSX
      Leading by example — well done! Everyone else: Don't forget to check if your company matches charitable donations made out to Fred Hutch.
    • WilsoInAus
      Post flagged for moderation. Science is not censored, but fake material is censored and fraud is illegal. The article is a fake posted on an open source bulletin board - the bulletin board has no association with any university or research facility. There are no such people as Bernard Middleton or Susan Cosgrove, that is just part of the fraud. Nothing has ever been published concerning Synergy supplements. Why? Because they are just supplements that have never been shown to have any effect regarding herpes. There is no scientific reason why they would and no effect in any study has been found. Yes it is completely unreasonable to persist as you are and you have been warned for your behaviour by the moderator, I'm sure they will deal with appropriately.
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Star33hcs

X -vax

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Cas9
Posted (edited)
1 hour ago, Star33hcs said:

https://www.nature.com/articles/s41541-020-0184-7 x-Vax Will have therapeutic use

It's definitely designed as a prophylactic but I believe they will also be testing it as a therapeutic. I didn't read the article; does it mention it being used as a therapeutic also?

Edited by Cas9

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Star33hcs
1 hour ago, Cas9 said:

It's definitely designed as a prophylactic but I believe they will also be testing it as a therapeutic. I didn't read the article; does it mention it being used as a therapeutic also?

Yes and amazing results

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JHenry
1 hour ago, Cas9 said:

It's definitely designed as a prophylactic but I believe they will also be testing it as a therapeutic. I didn't read the article; does it mention it being used as a therapeutic also?

Being non-scientific, I can’t make heads or tails, BUT it appears they are hard at work and that in itself is encouraging—we need a translation of the details into layman’s terms.   Henry.

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Cas9
Posted (edited)

@JHenry  @Star33hcs

I just read most of this paper. It did not appear that the experiments described in the paper, were for testing the vaccine's therapeutic potential. Others may have a different perspective.

In a nutshell, they infected a mouse with hsv1. They then administered a few different types of vaccines (in separate experiments).  Then they infected those now hsv1 seropositive mice with hsv2, and none of the vaccines provided complete protection from hsv2 infection.

On the other hand, when they used the ΔgD-2 vaccine (the one we are excited about and that X-Vax is developing), that vaccine did protect the hsv1 seropositve mice from subsequent challenge of hsv2. In other words, the ΔgD-2 vaccine acted as a prophylactic vaccine because it blocked/stopped the hsv2 infection from establishing a latent infection in the mice that already had an hsv1 latently established infection. Essentially, they got the same result as previous experiments (years ago) where they had vaccinated with ΔgD-2 vaccine in naive mice (uninfected mice), and then tried to infect them with hsv2.  In that case, as we all already know, there was no latent infection of hsv2; the ΔgD-2 vaccine completely blocked it.
Anyway, the key to the ΔgD-2 vaccine is that it elicits an ADCC immune response (not a gD neutralizing immune response like the other failed subunit vaccines) and this ADCC type of immune response stops the virus completely.

A therapeutic vaccine would be used for people who have an hsv infection, and where we want that infection to be held in check such that OBs are at the very least, significantly reduced in both frequency and intensity, and perhaps a reduction in shedding rates as well. That's what acyclovir does but it's simply not as effective of a therapeutic as we would like.

Further, acyclovir needs to be taken daily; at least during the OB.  On the other hand, a vaccine would be a shot or two for an entire year. That's one advantage of a vaccine. And of course if the vaccine did a better job at reducing the OBs etc than acyclovir, that would be a second benefit. Of course the ideal therapeutic vaccine would be one that stops OBs and shedding completely.

Edited by Cas9

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Garen
Posted (edited)

Hey read through it myself earlier. Cas9's write up is on point.

My main takeaways were they keep increasing the lethal dosage (using 100 times what kills a mouse 90% of the time from my understanding) and still seeing great results in terms of immunity.

Second (See picture attached from near the end of the paper)

This 1-time shot using the AADC immune response (purple) knocked out all trace of the virus in sacral ganglia to Log0!! (the data points with slashes through them were the mice that were injected with 100x the Lethal dose, even they were only 10Log2 compared to 10Log4 for non vaccinated)! Compare that to the normal exposure control vaccine  (orange) which at best were 10Log4.

  • Think about that one more time... a Mouse with X-Vax that was injected with 100 times a lethal dose of HSV2 had less 25-30% LESS HSV2 in their system than a mouse that was administered the base amount!

Do note that the control used here was NOT the one they were using earlier (similar to past failed vaccines). It does concern me that they did not do a 1:1 comparison here after putting 1:1 comparisons in other aspects of the study.

One downside I learned was this vaccine it doesn't' seem to be able to reach the triganglia at all, but overall X-Vax continues to look like our best shot at *something* that is curative in the near future.

In laymens terms if this Vaccine were for us:

An infected person getting this + having their uninfected partner get it could lead to a very normal/worry free sex life for both. I'd imagine an antiviral like Valtrex would still be apart of that equation.

Still, a positive study is a positive study 🙂

xvax results.JPG

Edited by Garen

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Garen
Posted (edited)

Second interesting graph that touches on my point immunity point above and Cas9's great description:

2 hours ago, Cas9 said:

@JHenry  @Star33hcs

In a nutshell, they infected a mouse with hsv1. They then administered a few different types of vaccines (in separate experiments).  Then they infected those now hsv1 seropositive mice with hsv2, and none of the vaccines provided complete protection from hsv2 infection.

On the other hand, when they used the ΔgD-2 vaccine (the one we are excited about and that X-Vax is developing), that vaccine did protect the hsv1 seropositve mice from subsequent challenge of hsv2. In other words, the ΔgD-2 vaccine acted as a prophylactic vaccine because it blocked/stopped the hsv2 infection from establishing a latent infection in the mice that already had an hsv1 latently established infection

Purple = X Vax

Green = Similar to Past Vaccine Trials

Black = Strictly the control Vaccine

As you can clearly see. the purple bar never goes down! HSV-1 infected mice have 100% survival against HSV-2 lethal doses. Very cool stuff.

xvax immunity.JPG

Edited by Garen

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JHenry
6 hours ago, Cas9 said:

@JHenry  @Star33hcs

I just read most of this paper. It did not appear that the experiments described in the paper, were for testing the vaccine's therapeutic potential. Others may have a different perspective.

In a nutshell, they infected a mouse with hsv1. They then administered a few different types of vaccines (in separate experiments).  Then they infected those now hsv1 seropositive mice with hsv2, and none of the vaccines provided complete protection from hsv2 infection.

On the other hand, when they used the ΔgD-2 vaccine (the one we are excited about and that X-Vax is developing), that vaccine did protect the hsv1 seropositve mice from subsequent challenge of hsv2. In other words, the ΔgD-2 vaccine acted as a prophylactic vaccine because it blocked/stopped the hsv2 infection from establishing a latent infection in the mice that already had an hsv1 latently established infection. Essentially, they got the same result as previous experiments (years ago) where they had vaccinated with ΔgD-2 vaccine in naive mice (uninfected mice), and then tried to infect them with hsv2.  In that case, as we all already know, there was no latent infection of hsv2; the ΔgD-2 vaccine completely blocked it.
Anyway, the key to the ΔgD-2 vaccine is that it elicits an ADCC immune response (not a gD neutralizing immune response like the other failed subunit vaccines) and this ADCC type of immune response stops the virus completely.

A therapeutic vaccine would be used for people who have an hsv infection, and where we want that infection to be held in check such that OBs are at the very least, significantly reduced in both frequency and intensity, and perhaps a reduction in shedding rates as well. That's what acyclovir does but it's simply not as effective of a therapeutic as we would like.

Further, acyclovir needs to be taken daily; at least during the OB.  On the other hand, a vaccine would be a shot or two for an entire year. That's one advantage of a vaccine. And of course if the vaccine did a better job at reducing the OBs etc than acyclovir, that would be a second benefit. Of course the ideal therapeutic vaccine would be one that stops OBs and shedding completely.

Thank you Cas, especially for keeping it simple and in layman’s terms.  Much appreciation, Henry.

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Cas9
3 minutes ago, JHenry said:

Thank you Cas, especially for keeping it simple and in layman’s terms.  Much appreciation, Henry.

Henry, that's because I AM a layman :)

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JHenry
3 minutes ago, Cas9 said:

Henry, that's because I AM a layman :)

😉

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byornk
Quote

This 1-time shot using the AADC immune response (purple) knocked out all trace of the virus in sacral ganglia to Log0!!

This is astounding and on-par with Keith Jerome's (at the Fred Hutch center) research on meganuclease-based removal of HSV plasmids from latently-infected cells.

However, if this relies on ADCC then I'm worried that the wholesale destruction of up to ~20% of the sensory neurons in our sacral nerve ganglion may have... negative side effects.

Quote

Antibody-dependent cellular cytotoxicity (ADCC) is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively destroys a target cell, whose membrane-surface antigens have been bound by specific antibodies.

 

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hk81

I think that you are reading something that is not written in the article. They don't write that the immune system is attacking the neurons. Probably ADCC is against the epithelial cells, and it avoids that the infection reaches the neurons

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Cas9
20 hours ago, byornk said:

This is astounding and on-par with Keith Jerome's (at the Fred Hutch center) research on meganuclease-based removal of HSV plasmids from latently-infected cells.

However, if this relies on ADCC then I'm worried that the wholesale destruction of up to ~20% of the sensory neurons in our sacral nerve ganglion may have... negative side effects.

 

The purpose of the vaccine is to prevent latent infection in the neuron, not to remove it once it's there. The latter is what Dr. jerome is working on; i.e. removing it after it gets in the neuron.

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MikeHerp
Posted (edited)

 

On 5/8/2020 at 7:47 AM, Garen said:

 

This 1-time shot using the AADC immune response (purple) knocked out all trace of the virus in sacral ganglia to Log0!! (the data points with slashes through them were the mice that were injected with 100x the Lethal dose, even they were only 10Log2 compared to 10Log4 for non vaccinated)! Compare that to the normal exposure control vaccine  (orange) which at best were 10Log4.

  • Think about that one more time... a Mouse with X-Vax that was injected with 100 times a lethal dose of HSV2 had less 25-30% LESS HSV2 in their system than a mouse that was administered the base amount!

One downside I learned was this vaccine it doesn't' seem to be able to reach the triganglia at all, but overall X-Vax continues to look like our best shot at *something* that is curative in the near future.

I'm excited about this vaccine and think it has a great chance to be approved.  However, this is not a "curative"vaccine.

The vaccine is not "knocking out" the virus in the ganglia.  Rather, it is preventing the virus from reaching the ganglia when the virus newly infects a living thing.  Once the virus is in the ganglia, I understand this vaccine does not reach there. 

On 5/18/2020 at 3:37 PM, byornk said:

This is astounding and on-par with Keith Jerome's (at the Fred Hutch center) research on meganuclease-based removal of HSV plasmids from latently-infected cells.

 

 

This vaccine is not removing the latent HSV.  Rather, it's preventing it getting there in mice that were previously uninfected.  That's an important difference with the FHC work which is curative.  The work X-Vax has published recently is prophylactic work.  

The vaccine may have therapeutic application--X-Vax has said it may.  But we will have to see further studies to see how much if any therapeutic user this will have.  

Edited by MikeHerp

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