HPV: Vaccine>’Natural’ Infection

Vaccines rock.

So many diseases my mom and dad, my grandparents had to deal with, had to fear– I never have to even think about. Viruses I read about in books, like a 5-year-old reads about dinosaurs.

And I really, really appreciate this fact.

Nowhere is this appreciation more vivid than with the HPV vaccine. Gardasil became widely available when I was 23, so I was still young enough that insurance humored me and covered the series of shots (though I had to harass the hell out of my OB/GYN at the time to actually get them). I feel like Indiana Jones, like I barely slid under a stone door before it trapped me in a room full of snakes.

I pretty much never have to worry about one of the major causes of cancer in women. Hell, Im never even really going to have to deal with ‘abnormal’ pap-smears (though I still get them annually anyway).

It feels amazing (YAY! I get to die from something else instead! LOL!).

But I learned something really cool about the HPV vaccine at that last conference I went to: The vaccine? It gives you a ‘better’ immune response than actually getting infected with HPV.

This is weird. Normally, a ‘natural’ infection from, say, chickenpox, activates every possible branch of your immune system. The ‘natural’ virus replicates over and over, over a period of time, and your immune response really has to rev up and think hard to ultimately fight it off. Once it does, you really dont need to worry much about getting chickenpox again. Contrast that to the best possible vaccine, a live attenuated virus, in the VZV vaccine. Live attenuated vaccines cover more bases than dead viruses/viral proteins, but even then, you have to readminister the VZV vaccine to keep immune protection.

And then weve got the HPV vaccine. Its not a live attenuated virus. Its not a killed virus. Its made of viral structural proteins mushed into a membrane (virus-like particles). This should be an ‘adequate-but-not-ideal’ vaccine, but its perfect. You make lots of antibodies to these structural proteins, get exposed to a ‘real’ virus, and it cant infect your cells. Hurray!

… But this isnt the case with a ‘natural’ HPV infection. HPV has evolved all kinds of these wonderful ways of dampening your immune response to it. Some people dont develop antibodies to HPV until months after they are exposed, and even then, they dont make very much, and even then, the antibodies dont really stick around long. I dont think there is any reason to think these antibodies provide much protection at all against future infection. Furthermore, there is evidence that in the ‘natural’ chain of events, from HPV–>cancer, ‘natural’ HPV proteins create an environment that is (accidentally) conducive to tumor formation:

In this model the potent immunosuppressive activity of iNKT cells is induced by epithelial hyperplasia as a result of persistent viral oncoprotein expression. This finding suggests that in skin settings of chronic infection, tumors or autoimmune disorders, where alteration or disruption of local epithelial architecture and physiology leads to hyperplasia, recruited iNKT cells may be acting via IFN-{gamma} to protect the tissue from a deleterious immune response, by generation of a local immunosuppressive site. Although this effect may be useful in dampening autoimmunity, the site also creates an immune privileged niche allowing further immune evasion by viruses and tumors, and generation of escape variants.

*blink* Yeah… ‘Natural’ is not better.

Comments

  1. #1 DataJack
    April 15, 2010

    Amazing. We truly live in an age of wonder.

  2. #2 peter
    April 15, 2010

    out of curiousity, I’ve always wondered, if the vaccines do prompt your immune system like that, why don’t they work after you’ve been infected too? i was generally under the impression that the reason you get a persistent infection like HPV is because your immune system doesn’t know what to do. once you ‘explain it’ with a vaccine why does it not work retroactively? I can understand in the case of chicken pox and the like as the course of the disease is short and conceivably quickly fatal. but in the case of a long-term infection I’ve never been quite sure why this wouldn’t work. could you explain?

  3. #3 ImagingGeek
    April 15, 2010

    @peter
    The answer to your question has to do with how your immune system “remembers” past infection.

    Your question has two answers, one from the immune side, one from the pathogen side:

    Immune Side:
    The cells in our immune system that create “memory” (T & B cells) do more than simply remember the antigen – they also “remember” the response the immune system made. Not only that, but you cannot separate the two – the antigen is remembered because the immune cell actually rearranges its DNA to make a receptor unique to that antigen. After that, all daughter cells (including the ones that turn into memory cells) have the same receptor and thus recognise the same antigen.

    At the same time, the immune cell also turns on/off the various response genes in a way which is essentially permanent (epigenetic control). As such, the RESPONSE to the antigen is also hard-wired and essentially immutable.

    So in general terms, the first time you respond to a pathogen is your one chance to get the immune response right; screw it up and future exposures will simply re-activate the deficient response. Hence, why vaccines cannot be used to “fix” an improper immune response – giving the vax simply reactivates the memory cells, whose functions are pretty much hard-wired in.

    Pathogen Side:
    Most pathogens that form latent infections have ways of avoiding the immune system. Some screw with the initial response, to ensure a proper immune response is not generated. Others hold out in cell types the immune system generally will not attack (neurons, for example). As such, even if you can rewire the immune response to one which will clear the pathogen, once established, the pathogen may still be able to ride things out.

    Vaccines generally prevent this from occurring by giving your immune system the tools to destroy the pathogen BEFORE the pathogen can do whatever it is the pathogen does to avoid immune clearance.

  4. #4 fishboy
    April 15, 2010

    @peter

    anecdotally, I have encountered a few cases of aggressively recurring genital warts that stopped recurring following the first two doses of the three-dose vaccine. One of these patients (who had had recurring anal warts for over a year) even reported coming back negative to a digene PCR test for HPV done on a rectal pap-smear taken between his second and third dose.

    I had hypothesized (after encountering the patient with the negative PCR test) that, perhaps, following vaccination the patients may have spiked a high enough titre of anti-HPV antibodies to clear the infection…of course, HPV infection has also been shown to clear up on its own after a while–so it could have just been a coincidence. Considering it now, it seems plausible that the warts cleared on their own and the patient was infected with a strain not detectable with the primers in the digene kit (which, conveniently, only detects the four strains the vaccine protects against).

    The most remarkable case that stands out in my mind was a patient who reported (when they came in for their second dose) that their condylomas “fell off” several days after receiving the first dose of the vaccine.

    It would be interesting to more systematically examine the possiblity that the massive immune response following vaccination (e.g. an initial spike in the serum concentration of antibodies against the viral proteins in the vaccine), would enable the body to clear infected cells and, ultimately, the infection.

    Anyhow, a couple interesting stories does not good science make…but it’s food for thought.

  5. #5 Mu
    April 15, 2010

    The effect of the vaccine triggering a different immune response than the pathogen isn’t new. All “after the fact” immunizations like rabies are based on more violent reaction of the immune system to the vaccine than to the infection itself. It’s amazing so that it happens in the case of a persistent infection like HPV, my guess is that the standard immune response doesn’t involve the particular protein used in the vaccine, and the immune response to the vaccine just happens to also affect the virus.

  6. #6 Noadi
    April 15, 2010

    You had the opposite experience from mine. My doc told me “you’re 25, it’s recommended up to 26 so lets get you started on the series right now while you’re still covered”. Then we still had to argue with the company about it because I’d turn 26 before finishing the series but I got it.

    It’s something I’m very happy I did and more so after reading this post.

  7. #7 peter
    April 15, 2010

    @ImagingGeek and @fishboy thank you very much both of you. ImagingGeek especially, that was a very clear explanation. I think the immune side of your explanation is the bit that I didn’t understand.

    as a further naive question, is anyone currently working on directly affecting the “memory” itself? or is that where mucking about with the immune system gets dangerous?

  8. #8 Optimus Primate
    April 15, 2010

    You’re ignoring the worst of all possible side effects, though: Gardasil turns you into a complete slut! Right? I mean, that’s what the Jesus people tell me. They wouldn’t lie, would they?

  9. #9 peter
    April 16, 2010

    what do you mean “worst”?

  10. #10 Cain
    April 16, 2010

    @8 Optimus Primate

    Worst?

    What are you talking about man? Bartles and James Blackberry Wine Coolers, a hot tub, and the HPV vaccine are my standard third date. 70% of the time it works every time!

    //amirite?

  11. #11 Claire
    April 16, 2010

    Luckly I was a complete slut before I got the gardasil jab so it hasn’t effected me.
    I find it strange that anyone could argue againist anything that could save womens lives and so easily 3 jab rather than operations and chemo, how sad would it be if a virgin til marriage didn’t get the vaccine then contracted HPV from a non-virgin husband.

  12. #12 MikeMa
    April 16, 2010

    Another very cool bit of info from Abbie.

    As for the slut aspects, that must be why you see all the godbots at the doors to clinics. They are waiting for dating opportunities.

  13. #13 ImagingGeek
    April 16, 2010

    @peter as a further naive question, is anyone currently working on directly affecting the “memory” itself? or is that where mucking about with the immune system gets dangerous?

    There is a lot of work going into that area. Autoimmune diseases (diabetes, MS, lupus, etc) occur when our immune systems accidentally respond to parts of our own bodies. There is a lot of work in that area trying to re-wire the memory of the immune system; usually by forming what are called “T suppressor cells”, specialised t-cells whose job is to make the immune system ignore something.

    It’s actually quite simple to completely reset the whole immune system – simply give the patient whole-body radiation, followed by a bone marrow transfer. The irradiation kills off all the old T and B cells, and then you repopulate the immune system from the new bone marrow.

    Obviously, that isn’t a method we want to use haphazardly; its great for dealing with leukaemia and other cancers of the immune system. Aside from that, its generally considered to dangerous for other uses (although it appears to have cured HIV in one patient…food for thought).

  14. #14 FreeSpeaker
    April 16, 2010

    IK am dealing with a person who is a devout anti-vaxxer who questions the source of your statement: “But I learned something really cool about the HPV vaccine at that last conference I went to: The vaccine? It gives you a ‘better’ immune response than actually getting infected with HPV.”

    Could you tell me where, when, etc. I would love to protoscope him with it.

  15. #15 ERV
    April 17, 2010

    FreeSpeaker– … who questions the source of your statement: “But I learned something really cool about the HPV vaccine at that last conference I went to: The vaccine? It gives you a ‘better’ immune response than actually getting infected with HPV.”

    Well, Im the source of that statement. NO ONE QUESTIONS THE MIGHTY ERV!!! hehehe!

    Its not really something that is backed up by just one person/one paper. Its more of a conclusion based on decades of research studying the immunology of an HPV infection and HPV virology, the immunology of the HPV vaccines, and some not-yet-published research I got to see at the conference.

    Like HIV Deniers and Creationists, if your anti-vax friend wants to ‘debunk’ that statement, theyre not just going to have to ‘debunk’ one paper or one person. Theyre going to have to deal with decades of basic immunology and virology.

    *shrug*

  16. #16 FreeSpeaker
    April 18, 2010

    The way your wrote it, i.e. “from the last conference” implies that there was a specific study/report/whatever that you were referring to. This particular anti-vaxxer liar is a real PITA, and I would love to proctoscope something specific showing the vaccine provides better immunity.

  17. #17 26Wings
    May 2, 2010

    my friend of three and a half years gave me hpv that she knew she had. she had also infected another one of our mutual friends a month prior, but neither of them said anything. She didn’t tell me that she had genital warts for seven weeks, which took away my opportunity to undergo any aggressive procedures to prevent implantation. I started the Gardasil cycle a week later and just got my second shot in March. Really I’m just afraid… I don’t know what is going to happen to me. I don’t know if the retroactive treatment will be helpful…and I don’t know if anyone will accept me.

  18. #18 Anonymous
    September 26, 2010

    26wings… 90% of hpv infections clear on their own ( mostly within a 1-2 year period ). Your immune system will fight the virus off. Don’t worry. It’s good you got the jab. there’s a lot of helpful information on the web out there. It’s not your fault, and you will be okay.

  19. #19 angela webber
    March 13, 2011

    how much were you paid to spew this bollocks?! Hpv kills girls. has already killed a 14 yr old and a 16 yr old. In Australia, 25 girls who had just received their first injection of the vaccine experienced headache, nausea, and dizziness. In some cases, the problems were so severe that they were hospitalized. Shares of the vaccine’s Australian developer, CSL, fell after the incident was reported in the news. do your research….and esp anyone ready this. people who are pro vaccine have something to gain. those that speak out dont….who do you trust? those profiteering or those who are looking out for the public interest and make nothing from doing so? google natural vaccines or whatever, you’ll read many articles about how bad vaccines are and how they destroy our natural ability to fight disease.
    PLEASE DO YOUR RESEARCH !!!!!

  20. #20 Charl
    March 14, 2011

    Angela – people feel dizzy, nauseous and faint all the time after vaccination, or indeed any procedure that requires sticking a needle into you – blood donation, blood tests, even just a stick with a sterile needle. Correlation =/= causation.