Can an HIV vaccine help aboriginal people in Saskatchewan?
- Thread starter petros
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US Scientists Expand Scope of HIV Vaccine Study | Africa | English
This is a decent review of where vaccine development is with respect to HIV. DNA vaccines are an active area of research right now, in fact I'm working on the development of one right now. We will be shipping heart tissue samples soon for histopathology. We are also considering an RNA platform.
RNA Molecules, Delivery System Improve Vaccine Responses, Effectiveness
The above link has some nice bits of information for those interested. The meat and potatoes is that the si-RNA, which basically interferes with RNA pathways, can be used to make sure that the vaccine is primed for the type of response desired. There has been a lot of work recently in my field examining which genes are up-regulated and down regulated by the plasmid in a DNA vaccine.
I think this would be a very good candidate for an HIV vaccine. By altering the pathways that are primed, potentially they could have a vaccine that doesn't allow the HIV to piggy back on the cellular response, and instead the infected cells would be destroyed. That at least would prevent much of the viral replication. Specific tuning could also provide stronger antibody response.
Of course this is still all hypothetical, and very much leading edge science, which furthers my point earlier about the limits of our technical abilities right now to effectively combat HIV with vaccines.
This is a decent review of where vaccine development is with respect to HIV. DNA vaccines are an active area of research right now, in fact I'm working on the development of one right now. We will be shipping heart tissue samples soon for histopathology. We are also considering an RNA platform.
RNA Molecules, Delivery System Improve Vaccine Responses, Effectiveness
The above link has some nice bits of information for those interested. The meat and potatoes is that the si-RNA, which basically interferes with RNA pathways, can be used to make sure that the vaccine is primed for the type of response desired. There has been a lot of work recently in my field examining which genes are up-regulated and down regulated by the plasmid in a DNA vaccine.
I think this would be a very good candidate for an HIV vaccine. By altering the pathways that are primed, potentially they could have a vaccine that doesn't allow the HIV to piggy back on the cellular response, and instead the infected cells would be destroyed. That at least would prevent much of the viral replication. Specific tuning could also provide stronger antibody response.
Of course this is still all hypothetical, and very much leading edge science, which furthers my point earlier about the limits of our technical abilities right now to effectively combat HIV with vaccines.
You looking to just cripple the virus and stop it from mutating healthy cells or a defense system that destroys the proteins?
Our DNA vaccine is attempting to build antibodies for the virus. The plasmid is injected into muscle tissue, and the muscle tissue begins expressing the proteins the plasmid DNA encodes for. So when the fish encounters the real virus, it recognizes it right away and uses the antibodies to provide protection against infection.
I should add, it's tricky business with fish. Evolutionarily, they have been endowed with a much stronger cell mediated response. All of the vaccines registered for fish utilize the humoral response. I hope to pitch an idea or two to my management soon to fund some graduate studies on this well known short-coming.
Cool so the fish makes it's own antibody proteins without introducing a crippled version of the virus through inoculation. Will it pass to the next generation as a permanent alteration?
Unlikely. We are conducting studies evaluating the distribution of the plasmid. It's not found in the gametes.
Sorry Petros; beg to differ:
Not me. I'm not in Sask. and I don't have HIV..............nor is/does any of me loved ones.
And I'm from totally immigrant Scotts/Irish/Limy ancestors. My great greats probably took part in the killing of Indians, and breaking the odd treaty, so I doubt if I'd be welcome in Sask.................or anywhere north of Ottywaw, even.
That does sound rather harsh, but: the Aboriginal Canadians have been kept uneducated and underemployed both by the white man and their own leaders.
Aids is spread by dirty needles, unprotected sex, and exchange of bodily fluids., and sometimes, as in the case of Lone Wolf's friend.........by accident. Since it is spreading like wildfire (we're told) in the Aboriginal communities, it must be that they DON'T KNOW. How could they not CARE. Or perhaps being addicted and drug-addled has something to do with it.
Everything starts with EDUCATION. That, in Canada, apparently, costs too much.
****!! I'm not in charge.
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Interesting stuff, Tonington. Do viruses behave similarly in fish as humans? Is there a FIV? lol
My brother works in the virology/immunology field. Now teaching at Trillium College. The following is an excerpt of an e-mail 2 years ago during the H1N1 scare. He mentions this trojan horse theory that I thought sounded similar to something you said above...
Don't know if you've been listening to H1N1 news but Dr. Donald Low (UofT/Mt.Sinai Hospital) has an interesting take on this. I've been wondering when somebody would finally pickup on the obvious from an immunology point of view. He thinks that the reason people that got flu shot last year are more susceptible to the (pandemic) pH1N1 virus than those that didn't get a vaccine, is because of the way the immune system works.
An antibody to the flu is what your trying to get your immune system to make when you get a flu shot (ie. pieces of flu protein injection). If you make an exceptionally good antibody then it will bind the virus whenever it passes by. An antibody is shaped like the letter "Y" and it is the arms of the "Y" that bind to the proteins (Hemagglutinin & Neuraminidase) extending from the virus. But once the flu virus enters your columnar epithelial cells (this takes less than a few minutes) in your trachea (throat) it will cause these cells to send out an alert to your immune system cells and calls for help.
I won't get into the biochemical pathways that elicit this response so I'll just put it in layman's terms. Macrophages (scavenger immune soldier cells) and T (thymus) and B (bone marrow) cells answer the call and arrive at the site of infection like first responders (ie. Fire, ambulance etc.). Macrophages have scavenger receptors (think of these as loops) attached to their surface. When the stems of the Y-shaped antibodies bound to virus pass by these macrophages the fishing begins. On the stem portion of the "Y" at the bottom is a hook which is designed to be caught by the macrophages. Once the "Y" with it's viral cargo is hooked by the macrophage a process called phagocytosis (means engulfing or swallowing) begins and the antibody and it's cargo is swallowed by the macrophage into a cage like phagosome (endosome).
Donald Low thinks this is how the virus is gaining entry to the cells and I agree. It's like a trojan horse virus that allows itself to be caught so it can gain entry to the city. Once inside the cell the natural proton pumps in the endosomal membrane start working and slowly acidify the contents as this endosome is merged with a lysosome (bag of digestive enzymes). These enzymes are activated by the acidic pH caused by the proton pumps and this is the most important part for the virus. It waits for these enzymes to split the Hemagglutinin exposing a viral fusion peptide that drills into the wall of the endosome (the cage where the virus has been held captive) and the virus breaks into the cytoplasm of the cell where it is free to attack the nucleus (brains of the cell) which is now udefended. Inside the nucleus the virus rapes all the women and makes tons of baby virions (layman's terms). "The horror, the horror".
Well, that's it in a nutshell. Stay tuned next week for the next exciting version of viral games. Next week starring Daffy Duck who goosed the Gander & the migratory flight path of the virus followed by "Vacationing in Mexico". Aqua caliente.
================
yeah, ok, so he's a bit of a ham.
My brother works in the virology/immunology field. Now teaching at Trillium College. The following is an excerpt of an e-mail 2 years ago during the H1N1 scare. He mentions this trojan horse theory that I thought sounded similar to something you said above...
Don't know if you've been listening to H1N1 news but Dr. Donald Low (UofT/Mt.Sinai Hospital) has an interesting take on this. I've been wondering when somebody would finally pickup on the obvious from an immunology point of view. He thinks that the reason people that got flu shot last year are more susceptible to the (pandemic) pH1N1 virus than those that didn't get a vaccine, is because of the way the immune system works.
An antibody to the flu is what your trying to get your immune system to make when you get a flu shot (ie. pieces of flu protein injection). If you make an exceptionally good antibody then it will bind the virus whenever it passes by. An antibody is shaped like the letter "Y" and it is the arms of the "Y" that bind to the proteins (Hemagglutinin & Neuraminidase) extending from the virus. But once the flu virus enters your columnar epithelial cells (this takes less than a few minutes) in your trachea (throat) it will cause these cells to send out an alert to your immune system cells and calls for help.
I won't get into the biochemical pathways that elicit this response so I'll just put it in layman's terms. Macrophages (scavenger immune soldier cells) and T (thymus) and B (bone marrow) cells answer the call and arrive at the site of infection like first responders (ie. Fire, ambulance etc.). Macrophages have scavenger receptors (think of these as loops) attached to their surface. When the stems of the Y-shaped antibodies bound to virus pass by these macrophages the fishing begins. On the stem portion of the "Y" at the bottom is a hook which is designed to be caught by the macrophages. Once the "Y" with it's viral cargo is hooked by the macrophage a process called phagocytosis (means engulfing or swallowing) begins and the antibody and it's cargo is swallowed by the macrophage into a cage like phagosome (endosome).
Donald Low thinks this is how the virus is gaining entry to the cells and I agree. It's like a trojan horse virus that allows itself to be caught so it can gain entry to the city. Once inside the cell the natural proton pumps in the endosomal membrane start working and slowly acidify the contents as this endosome is merged with a lysosome (bag of digestive enzymes). These enzymes are activated by the acidic pH caused by the proton pumps and this is the most important part for the virus. It waits for these enzymes to split the Hemagglutinin exposing a viral fusion peptide that drills into the wall of the endosome (the cage where the virus has been held captive) and the virus breaks into the cytoplasm of the cell where it is free to attack the nucleus (brains of the cell) which is now udefended. Inside the nucleus the virus rapes all the women and makes tons of baby virions (layman's terms). "The horror, the horror".
Well, that's it in a nutshell. Stay tuned next week for the next exciting version of viral games. Next week starring Daffy Duck who goosed the Gander & the migratory flight path of the virus followed by "Vacationing in Mexico". Aqua caliente.
================
yeah, ok, so he's a bit of a ham.
Viruses do pretty much behave the same. The result can be quite different though. Koi herpes will kill close to 100% of the population. Human herpes not so much, but give Paris Hilton some time and I'm sure she'll produce a potent mutation...
There's a number of different hypotheses for why seasonal influenza lead to higher risk of pH1N1 infection, though even that is a contentious claim. Similar studies were performed in many countries, with mixed results. Observational studies are inherently uncertain, as there are no real true controls. In our labs we use fish that are naive, as we call them. Their immune profile is clean, no infection, no immunization, no background levels of bacteria/virus that you would have in the wild, or in a Toronto shopping mall for the human counter-example.
If the finding of increased risk turns out to be true, it's difficult to determine why without access to a large bank of blood serum across many demographics, with before and after samples. You need that for meaningful comparisons of the baseline immune profile and that during/after infection.
There's a number of different hypotheses for why seasonal influenza lead to higher risk of pH1N1 infection, though even that is a contentious claim. Similar studies were performed in many countries, with mixed results. Observational studies are inherently uncertain, as there are no real true controls. In our labs we use fish that are naive, as we call them. Their immune profile is clean, no infection, no immunization, no background levels of bacteria/virus that you would have in the wild, or in a Toronto shopping mall for the human counter-example.
If the finding of increased risk turns out to be true, it's difficult to determine why without access to a large bank of blood serum across many demographics, with before and after samples. You need that for meaningful comparisons of the baseline immune profile and that during/after infection.
...& here I thought he was setting you up for a, "Is that a Trout in your
pocket, or are you Paris Hilton?" type of follow through.
pocket, or are you Paris Hilton?" type of follow through.
The recent issue of Science has some good research with potential for use in universal influenza vaccine development. The reason why we need to make new influenza vaccines all the time is because the hemagglutinin is not highly conserved in the influenza genome, it changes rapidly. Well that's not entirely accurate. Hemagglutinin is made up of two pieces, a stem, and the globular head region. The head region is where all the diversity is, and it turns out that the stem actually is highly conserved.
Recent research has identified broadly neutralizing antibodies, which attack the stem portion of hemagglutinin, which prevents the virus from entering the cell. It will still attach, but will be unable to move inside and infect the cell. This means that across all H subtypes (16), protection can be provided against severe influenza. So the trade-off is that these antibodies aren't quite as potent as the conventional vaccines which provide specific protection against the globular head of hemagglutinin. But as they act on a portion of the genome that does not change, this could be a very useful vaccine in that we wouldn't need to re-tool vaccines continuously.
These broady neutralizing antibodies (bnABS) have been described before, but more is being learned about them. For example, vaccines which provide specific protection tend to produce antibody titers that reduce after exposure, while these bnABS maintain levels in the blood fairly consistently. So the question becomes, how to make these bnABS more effective? It appears that the commonly used inactivated vaccines do not stimulate levels, while live virus (attenuated or not) and DNA vaccination do stimulate production, due to the presence of active protein expression.
Very interesting work.
Eckiert et al. 2011
Corti et al. 2011
Recent research has identified broadly neutralizing antibodies, which attack the stem portion of hemagglutinin, which prevents the virus from entering the cell. It will still attach, but will be unable to move inside and infect the cell. This means that across all H subtypes (16), protection can be provided against severe influenza. So the trade-off is that these antibodies aren't quite as potent as the conventional vaccines which provide specific protection against the globular head of hemagglutinin. But as they act on a portion of the genome that does not change, this could be a very useful vaccine in that we wouldn't need to re-tool vaccines continuously.
These broady neutralizing antibodies (bnABS) have been described before, but more is being learned about them. For example, vaccines which provide specific protection tend to produce antibody titers that reduce after exposure, while these bnABS maintain levels in the blood fairly consistently. So the question becomes, how to make these bnABS more effective? It appears that the commonly used inactivated vaccines do not stimulate levels, while live virus (attenuated or not) and DNA vaccination do stimulate production, due to the presence of active protein expression.
Very interesting work.
Eckiert et al. 2011
Corti et al. 2011