HIV-1 CTL Vaccine: lol, we are screwed.

Posted by ERV on December 3, 2010
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Glance back at this post for a refresher on what Im going to write about here.

Quick recap:

HIV-1 usually evolves around this to ‘hide’ from CTLs. Maybe it puts a sombrero on the skull so the CTLs think its a party boat. But while HIV-1 evolves ways to hide from cytotoxic T-cells, this escape comes at a fitness cost. So if the sombrero-pirate-flag-HIV is transmitted to someone with a different MHC type whos CTLs couldnt see that pirate flag in the first place, HIV-1 is going to take off the sombrero and regain fitness.

The Problem: HIV-1 is figuring out how to evade CTLs… while maintaining fitness.

HIV-1 is never taking the sombrero off. Even if it is being transmitted to someone who does not put up a pirate flag with a skull, the sombrero isnt going away. So then if the person who puts up a flag without a skull on it transmits to someone who does put up a flag with a skull, the sombrero is still there, and HIV-1 can escape their CTL response with absolutely zero effort. How?

A paper was just published in PLOS Pathogens, where they made a mathematical model that explains what is going on. Basically, escape from CTL responses, on a global scale, can be measured in years. Reversion of those escape mutations can be measured in decades.

Modelling the Evolution and Spread of HIV Immune Escape Mutants

Yes, we can find and describe individual transmission pairs, where one persons HIV-1 puts on the sombrero hat, and then gets transmitted to someone else who doesnt present a skull, and the sombrero goes away. Environmental pressure–> Selection of escape variant–> Relief of environmental pressure–> Reversion. Dir. But when we look at the population, world-wide scale, HIV-1 is learning how to pick our locks. All of our locks. At the same time. Its escaping our immune responses much faster than it ‘forgets’ and reverts.

If we are going to make an HIV-1 vaccine to stimulate the CTL branch of our immune system, we need to do it NOW, or it is never going to happen. HIV-1 will figure out how to be invisible to an entire branch of our immune system. All of us.

This doesnt just suck for vaccines, either. Slower disease progression is associated with a strong initial CTL response. If youre infected with a variant that, from Day 1, can escape your CTLs…

:-/

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Comments

  1. #1 daedalus2u
    December 3, 2010

    Does this mean that a really good thing to do to help a vaccine effort eventually be successful is to treat as many people with HIV now to reduce their virus burden and reduce transmission so that these bad mutations and reversions don’t have as many chances to happen?

    This would be in addition to saving the lives of all those people who have HIV.

  2. #2 theshortearedowl
    December 3, 2010

    In population genetics reverse mutation generally happens at a rate 10 times slower than forward mutation. Worryingly, that is what you would expect from a neutral mutation, which does suggest that HIV has somehow got around the fitness cost of evading CTLs. How’s that vaccine coming?

  3. #3 W John Martin
    December 5, 2010

    HIV is hardly a threat in this regard, in comparison to many other viruses, bacteria and viteria. The Stealth Viruses which cause most Gulf War Syndrome and many CFS cases for example evade not only CTL but also antibody responses. Likewise although some very weak antibody responses to XMRV have been detected, the titer is never significant.

    Alternative cellular energy pigments from bacteria of stealth virus infected individuals.
    Martin WJ.
    Exp Mol Pathol. 2005 Jun;78(3):215-7. Epub 2005 Mar 23.
    PMID: 15924874

    Stealth adaptation of an African green monkey simian cytomegalovirus.
    Martin WJ.
    Exp Mol Pathol. 1999 Apr;66(1):3-7.
    PMID: 10331958

    Stealth virus epidemic in the Mohave Valley. I. Initial report of virus isolation.
    Martin WJ, Anderson D.
    Pathobiology. 1997;65(1):51-6.
    PMID: 9200190

    African green monkey origin of the atypical cytopathic ‘stealth virus’ isolated from a patient with chronic fatigue syndrome.
    Martin WJ, Ahmed KN, Zeng LC, Olsen JC, Seward JG, Seehrai JS.
    Clin Diagn Virol. 1995 Jul;4(1):93-103.
    PMID: 15566831

  4. #4 Jonathan
    December 5, 2010

    HIV gives us so many problems, not because it’s such a good virus in and of itself. HIV just happens to fit well into the holes in our medical knowledge/ability. The environmental constraints to HIV are those vectors that we can fight. Thus HIV is prone to evolving only within the gaps in our current knowledge. That means HIV is hard to fight because we’ve found it so hard to fight HIV. A bit of a tautology but still a good lesson in evolution.

  5. #5 Orakio
    December 6, 2010

    Disheartening, yes, but I can’t say that it doesn’t make sense.

    Unfortunatey, I am also now going to be personifying HIV as hundreds of mexican pirates wielding giant bottles of tequila, and AIDS as the hangover that won’t leave.

  6. #6 IanW
    December 7, 2010

    Keep up the good work! It’s nice to know that there are still bloggers here who haven’t forgotten what “science blogging” actually means!

  7. #7 theshortearedowl
    December 7, 2010

    Viteria? Srsly?

  8. #8 Sandi
    December 7, 2010

    DNA vaccines have shown strong Cell Mediated responses in early trials. There are a few trials ongoing. Only time will tell.