This is kind of interesting:
A new AIDS vaccine tested on more than 16,000 volunteers in Thailand has protected a significant minority against infection, the first time any vaccine against the disease has even partly succeeded in a clinical trial.
Scientists said they were delighted but puzzled by the result. The vaccine — a combination of two genetically engineered vaccines, neither of which had worked before in humans — protected too few people to be declared an unqualified success. And the researchers do not know why it worked.
“I don’t want to use a word like ‘breakthrough,’ but I don’t think there’s any doubt that this is a very important result,” said Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, which is one of the trial’s backers.
Now obviously I do not understand the science of this one bit, but I thought you could not make a vaccine for AIDS because it mutated so quickly. Maybe Tim F. can explain.
I would think that even if it mutates wildly there should still be some aspects that would not change or would still be affected even if they did change. But I’m a civil engineer not a biochemgenepathozoologist.
The AIDS virus does mutate, but it still has to attack our cells a certain way. If you can block that connection, the virus can’t work.
Those words: “Protected too few people”. Were they doing actual HUMAN trials on this? How much does it suck for the majority who this didn’t work for…and now have HIV.
My guess is the volunteers came from at risk populations that can’t or won’t practice safe sex. I wouldn’t be surprised to learn a large number of the volunteers are in the sex trade.
Not saying it’s right or good, but it’s where I’d put my money if you asked me where the volunteers came from.
The rapid mutation of HIV is indeed a problem, as you note. These vaccines (yes, plural) targeted strains currently circulating in Thailand, but might not work as well or at all on other strains and furthermore the Thai strains could easily evolve or just drift away from it over time. We don’t know.
Most important, the degree of efficacy is far too low for this to actually be used. If you give people a vaccine which is not highly effective, it will be counterproductive. Many people will use that to rationalize unsafe behavior, believing themselves to be protected, and you could end up actually increasing the rate of transmission. Whether this trial actually gives any hope or represents any progress toward an effective vaccine is unclear, but in my view, doubtful.
NIH shows 118 clinical trials for HIV vaccines in process or completed. At some point, clinical trials on real, live, actual human-type beings are pretty much necessary to determine the real efficacy of any drug. Generally recruitment comes from at-risk populations, and participants are well-informed volunteers. Researchers don’t just sidle up to people and say, “Here you go, a vaccination against HIV. Go screw yourself to death.”
Combining two things that didn’t work to make something that might isn’t such a bad idea if the two things that didn’t work were based on valid ideas.
As for the ethics of the test, I’m sure no one was told that the possible vaccine was a surefire way to avoid AIDS. The recipients may have wanted to believe that, but I have serious doubts that any of them acted very differently because they thought they might have been immune because they were part of a test.
All I can really say is that I’m glad scientists are actually looking at what didn’t work rather than just rushing headlong towards the next big thing. I imagine AIDS research has led to more medicines and innovations and knowledge about ourselves than the opponents will ever admit. Seeing scientific advances in terms of More Buttsex and Less Buttsex isn’t a great way to run a research project funding source. Unless you’re into wetsuits or are Dan Savage, of course.
We’ve been talking a bit about this in my master’s classes last year. Basically, HIV and other viruses have certain patterns to their infection cycle. Currently there has been headway in trying to find sites on the virus or parts of the pathway that are good “blockers” for the virus.
The most obvious is binding to the cell, if it can’t enter the cell, it can’t infect the cell. The binding pattern though is pretty complex and mutates pretty well, but there were some successes in blocking secondary binding mechanisms (HIV fuses with the host cell by essentially binding and then winching itself into the cell membrane), reverse transcriptase blockers and most successfully (I believe) either replication or recruitment blockers which means a cell might get infected, but it can’t itself become infectious.
The vaccine stage is because in the last year or two, we’ve been finding a few spots and chinks in the chain that are fairly conserved and thus targetable.
Obviously, we’re not in the a vaccine on the shelf stage as this number is pretty low and the virus may develop a workaround the blocking mechanism, but what this does mean is that we’re finding enough blockers to design pretty good medicine for those currently suffering and we’re getting close to some real preventative care on an issue that used to be considered unsolvable.
It can only mutate so many ways. To be “effective” (read: remain a virus), it must hold some processes constant, and most likely it’s mode of entrance into cells and/or its process of reverse transcription. If you can block its growth or entrance on those strongly conservative pathways, you’ve probably won.
Note the probably. Viruses and bacteria always find a way to eventually get around these roadblocks. See: bacteria, antibiotic-resistant.
Yup, for instance, HIV and H1N1 have similar problems in regards to their different subparts mutating at different rates and recombining as some structural similarities.
Basically, work on one virus could lay most of the groundwork for success on another virus and will at least give deep understanding to all retroviruses.
For an even more clear one-to-one relationship. AIDS research made gene therapy a possibility. So the whole stem cell debate and it’s potential uses for curing chronic diseases is only possible because of focus on retrovirus patterns kicked off in the hunt for the AIDS cure.
Also, the fact that it’s
a) lysogenic (not uncommon, but harder to deal with in immunological terms- see chicken pox coming back as shingles for an example of this)
b) attacks white blood cells specifically, making a vaccine based response incredibly hard to trigger;
…have both conspired to make HIV/AIDS the gold standard for ratfucker diseases. It’s really just the perfect disease in terms of coming along just as we thought we had a handle on “modern medicine” and could cure anything, in terms of it being perfectly designed to slip around our 1980’s era medical approaches.
@PaulW: Very well put.
So I guess the best thing to do is not to make HIV die, but to mutate it into something that would make its sufferers do something other than die slowly. If there was a way that the virus could be mutated into something that would make the sufferer crave a hot cup of something made with Folgers crystals, this thing would have been cured ten years ago. So how about it, genetic researchers? Get some funding from Coca-Cola, Pepsi, Funyuns, or Slim Jim, make some changes, and Profit!
This vaccine “works” on the same principles as the inhibitor cocktail does. The assumption is even if one part mutates towards resistance, the other target can still work. Getting two resistance mutations is harder than getting one. Getting 3, harder still. It is still a numbers game, and eventually resistant strains will emerge. Same game as with antibiotics…
OT, but is anyone watching Obama chairing the Security Council meeting? Hillary is sitting behind him and she looks positively sick. I mean, she looks like she has not slept in weeks.
This is weird. Must be about 18 years ago now a friend of mine asked me if I thought there would ever be a cure for AIDS. I said I thought there would be, but that it would probably require fundamental advances in medicine, at least some of which would probably come about as a direct result of the search for a cure for AIDS; would probably involve genetic research, which was still kind of a baby science at the time; and might take decades.
That conversation just popped into my head when I read your post just now. It was kind of an eerie feeling.
@CalD: When my parents moved, I had to clean all my old crap out of their house, and I found an old science magazine talking about the first evidence that HIV (can’t remember if they’d even identified it as such at that point) might jump from the gay population to the straight population. It was a really weird feeling– the ignorance of bisexuality, the lack of awareness of other ways of transfusion, the fact that it was still a ‘fringe’ disease as far as mainstream media were concerned.
@Persia: If you want to be even more maddened by that lack of awareness, consider that the epidemiology of hepatitis B was already pretty well understood by that time, and it’s transmitted in the same ways as HIV.
The vaccination conspiricists would be very interested in the reported involvement of the US military in the trial.
I’m not sure the results are statistically significant. Out of over 16395 participants, only 23 more wound up with HIV in the unvaccinated group than the vaccinated group. With the number of trails going on around the world, it is statistically likely that at least one would give a false positive of this magnitude.
Still, bears further investigation. They are only three years into it. If the trend continues, there could be something to it.
Vaccines work by sensitizing the immune system to the protein coat of a virus. Antibodies then attack the virus in the bloodstream, triggering an immune response by the white blood cells, which attack the viruses.
Unfortunately, as mentioned above, HIV specifically attacks white blood cells, so his has been a huge problem. Also the rapid mutation rate means that the protein coating of the virus changes often enough that sensitizing the immune system to one particular strain of the virus doesn’t suffice to trigger an immune response to other variants of the virus.
As mentioned above, there are other ways of blocking a virus. You can prevent it from binding with the cells it targets, in this case, the white blood cells. In order to infect a cell, a virus must inject the RNA contained inside its protein shell into the target cell. If it can’t do that, the virus becomes ineffective.
Failing that, you can still try to block HIV from replicating by preventing it from releasing new virus particles from the cells it infects. So there are a number of strategies for dealing with a retrovirus like HIV but so far, none of them have been completely effective.
@Persia: Funny you mention that. I just purchased a copy of Colors magazine from 1993 dealing specifically with HIV/AIDS. (bought it because I’d been searching for years for the image the magazine doctored to give Reagan Kaposi’s Sarcoma.) It’s still strange to recall those days, and to still see messages like, “You can’t get AIDS from mosquitos.” Then again, in 1996, I was at an LGBT activists conference, and the wait staff decided to wear latex gloves to serve our conference, and only our conference….
@MAJeff: Around that time I killed the only article I outright killed in my brief and glorious career as a college newspaper editor. (It was an ‘HOMG! Greg Louganis could have KILLED ALL THE PEOPLE IN THAT POOL’ article.) I said, basically, I think your article is really angry and not what you’ll be proud of tomorrow, and also you are completely stupid about HIV. You can edit it and I’ll run it as long as you take out the crap about HIV, because I’m not putting bad science in my newspaper.
He didn’t resubmit it.
James K. Polk, Esq.
The two components of the vaccine are:
ALVAC that utilizes a canarypox variant that has been genetic engineered to contain three HIV genes (env, gag and pol I believe). These work as a version of an attenuated virus (with no possiblity of infection) to stimulate antibody growth against the surface antigens on HIV virions.
AIDSVAX is a purified, recombinant gp120 (the protein that binds to white blood cells). This stimulates antibody production against that specific antigen. They thought, as this is where the virus interacts with the cell, that this region would be conserved enough (constant between generations) to effectively deactivate HIV. I think they were never able to get a sufficent enough native immune response to protect or cure.
Agreed. Right-wing bigots go on and on that research monies should be directed at cancer, not AIDS. But in retrospect, while cancer is worthy of funding in general, a lot of that research appears to have gone nowhere, whereas the AIDS stuff actually produced results which presumably might have wider application.
Sad to say there is no hope of a solution to the problem that AIDS mutates quickly.
One can make a vaccine for a virus that mutates quickly, it just doesn’t work for many years. For example, influenza mutates quickly. Last years influenza vaccine is useless. So every year they make a new vaccine.
The hope and dream is that AIDS vaccines might be like influenza some day.
The test made a vaccine designed to work against HIV currently in Thailand. Even if it worked perfectly, it wouldn’t work in other areas of the world and wouldn’t work in Thaliand in a few years.
The case of HIV is much worse htan the case of influenza. All vaccines tested until this one haven’t worked at all ever.
Now it is conceivable that if they develope a vaccine that works against AIDS it will stimulate antibodies that stick to a critical part of the HIV virus so if the virus mutates so the antibodies don’t stick, then the virus won’t infect human cells at all (the mutation will be doomed from the start with or without vaccine).
But right now doctors would be ecstatic if the only problem were that the virus mutates so they have to make a new vaccine every year. It’s much much worse than that.
I see I contradicted myself with “no hope” of something which is “conceivable”. Not quite a logical contradiction as one can conceive of something impossible (I just imagined having a rational discussion with a teabagger).
I’d say, however, that there is a very sadly very low hope that an AIDS vaccine will ever be like, say, the small pox vaccine and drive the virus extinct or even like polio etc and make the virus a major problem only in countries without decent public health systems.
Like PaulW and Punchy (and others sorry if I missed you upthread) I do hope, but barely.
The problem with research is that you can only know these kinds of things “in retrospect.” I doubt the first people studying the semiconductor ever even conceived the idea of a computer. Franklin certainly had no idea what electricity would turn into.
To those of you stating: HIV mutates, so even if we find a vaccine, it’ll just mutate and keep spreading.
HIV isn’t the flu. HIV isn’t airborne. HIV is, in fact, rather hard to get — it requires transmission of bodily fluid, and saliva alone won’t cut it. You can’t get it from drinking after someone, being in the same room when they sneeze, or kissing them.
HIV spread is pretty much entirely by unprotected sexual contact, now that blood supplies are routinely screened.
The flu’s mutation rate is a serious block to vaccines, because as soon as a new varient arises it’ll spread easily into a population.
HIV, on the other hand — if you vaccinate against current strains, the infection vectors still have to be sexual. New strains will spread slowly — very slowly — and have to come from HIV positive people who are having unprotected sex, have evolved a mutation that slips past a vaccinated populace, and who aren’t reacting well to drug therapies and thus have a large enough viral load to spread it through sex.
If you can vaccinate the populace at large against the most common strain(s), and medicate those with HIV to keep their viral load low (and some cocktails drop it to darn near undectable), you will cut off the primary avenues of infection — which means that mutated HIV isn’t really a problem.
Comparing HIV to the flu is a good metaphor in that both are highly mutable viruses. Comparing them in terms of how they spread — and would react to even weak vaccines — is not. HIV is very hard to spread compared to the flu. You can’t even compare them.
Umm….well….I don’t think the traditional vaccine model is favored for HIV prevention.
I think most productive research is in RNAi and nucleic-acid based therapies for both pandemic flu vaccines and high mutate rate viruses.
Were they using RNAi vaccines in the study?
It just says “genetically engineered vaccines”.
Wrong link above. Right one.
Ty cassidy…is that what they used?
Mutagenic enhancement is also a product area of research, but “genetically engineered vaccines” sounds more like RNAi.
Agreed, but that doesn’t detract from my point that right-wing arguments against AIDS research were (unsurprisingly) idiotic.
I’m pretty sure this was a standard protein-based vaccine, no RNAi. The “genetically engineered” bit probably refers to the insertion of HIV genes into the canarypox vector or the recombinant gp120 in the AIDSVAX portion of the cocktail.
Haven’t strains of HIV and AIDS been found to be tens of thousands of years old plus people that have been found to be immune to the disease?
now would be a good time to buy stock in whatever company plans on rolling out the AIDS vaccine final product
Um, wha? The oldest confirmed strain of HIV I’m aware of is from a blood sample taken in the ’50s. SIV (Simian Immunodeficiency Virus), HIV’s close cousin, has probably been around a lot longer, but all evidence points to a fairly recent origin of HIV itself.
Ah this is what I was trying to recall. Ancient HIV strains and HIV like diseases have been found dating very long ago some tens of millions of years ago others tens of thousands ago.
http://www.sciencecentric.com/news/article.php?q=08100102 states the strain that was responible for the AIDs epidemic originated between 1884 and 1924.
But for the life of me I cannot recall the info that said the reason some people were immune to HIV/AIDs was due to a previous disease strain that would have rampaged throughout prehistoric tribes about twenty or thirty thousand years ago. This was about eight or nine years ago so maybe it was found to be in error.
@Mr. Poppinfresh: Worth clarifying the difference between lysogenic (essentially viruses that reproduce in living cells) and lytic (viruses that kill their hosts as they replicate) virii..
@Skalite: No, to avoid a repeat of Tuskegee, grant proposals for studies on human subjects are all reviewed for these kinds of issues.
In this case, they got approval for the study by giving the subjects training in safe sex and condom use, and also by guaranteeing lifelong, free antiretroviral treatment if any subject (either in the experimental or control group) came down with AIDS.