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Will We Soon Have an Effective Vaccine against HIV? Not Until We Can Make a Superman or a Bionic Woman
May 26, 2009
World AIDS Vaccine Day was May 18. Where do we stand? As an economist, I’m going a bit out on a limb here, blogging about biology. Hopefully blog readers will correct my worst errors. But here’s my read …
Remember the story about how Pasteur discovered vaccines by observing that milkmaids had clear complexions? Having been exposed to the antigens in the cowpox virus, the immune systems of these French women generated antibodies which then could attach themselves to the similarly shaped smallpox virus, allowing immune system hunter-killers to destroy smallpox virus particles and protect the women from the disfiguring and often fatal scourge. This approach is still the primary strategy for developing vaccines, and will be followed in developing a swine flu vaccine, for example. However, so far it has not worked for HIV.
Out of frustration, researchers have turned to the other major component of the immune system, the so-called T-cell, in the hope that by stimulating its response to HIV they could at least partially protect against infection and perhaps slow the progression of those infections not prevented. The disappointing and disheartening STEP vaccine trial of 2007, which had to be halted when it appeared that the vaccine actually facilitated HIV transmission rather than preventing it, followed this second and less intrinsically promising strategy.
So here’s the new idea: Instead of trying to teach the human immune system how to make the right antibodies, how about endowing the human body with an entirely new capability – the ability to generate HIV-specific antibodies regardless of previous exposure to any fragments of HIV. If people with this ability were exposed to real HIV, their artificially generated antibodies would already be available to tag the virus so the hunter-killer cells could immediately join the chase.
Researchers led by Philip Johnson at the Children’s Hospital of Philadelphia have just announced success at doing almost exactly that – but so far only with mice and monkeys. [See the Nature Medicine article and the Philadelphia Inquirer story.] They inject these animals with a harmless virus that has been genetically modified to take up residence in muscle tissue and “express” selected HIV antibodies, which then circulate in the animal’s body. The researchers refer to these “bionic” antibodies as “antibody-like immunoadhesins”. I guess that’s because, although they were not generated by an organic immune system, they behave like real antibodies in tagging or “adhering” to the HIV particle.
To me this sounds like science fiction. The term “anti-body like immunoadhesions” could have been dreamed up by a Star Trek special effects tech. People whose immune systems are enhanced in this way will actually be superhuman, since they will be endowed with a new biological capability, a kind of programmed invulnerability to HIV. Since their own genes would not be modified, their new ability would not be heritable by their children. They would be more like the “bionic woman” or the protagonist of “Alias” than like the genetically evolved “X-men”.
Although achieving this objective in animals might be an exciting breakthrough in immunology, with numerous lucrative benefits outside of HIV, this progress towards a new way to achieve antibody protection should not make us complacent regarding HIV prevention. Neither mice nor monkeys have proved very useful in the past for predicting how a HIV drug or vaccine would perform in humans. Injecting human beings with genetically modified viruses must proceed slowly and carefully, for fear of noxious side-effects that have not been detected in the animal studies. Only after safety has been rigorously demonstrated, will efficacy trials be possible – and they may not work as well in people as they have in animals. As Seth Berkeley, the President of the International AIDS Vaccine Initiative, says in his new posting in honor of AIDS Vaccine Day,
“[T]hese developments will not lead us directly to an AIDS vaccine. There is much work to do, and more failure ahead, certainly. But the point is, despite disappointments, overall, AIDS vaccine science is progressing.”
So on World AIDS Vaccine Day I am left with the thought that there is no magic medical breakthrough which will come along soon enough to prevent the next several millions of cases of HIV infection. On the vaccine front, “there is more failure ahead.” While vaccine researchers continue to investigate new ideas like those reviewed by Seth, hoping that supermen and bionic women lie in our future, the only prospect for slowing HIV transmission for the coming decade or more lies in strengthening HIV prevention though behavioral change. The techniques of randomized controlled trials and large scale experimentation in the search for an HIV vaccine, and the financial resources that have supported them, now need to be deployed in earnest to test the effectiveness of behavioral change interventions. Mechanisms like the advanced market commitment should be used to stimulate private sector financing of HIV vaccine research, so that public HIV prevention resources focus primarily on researching behavioral change interventions.
2 Responses to “Will We Soon Have an Effective Vaccine against HIV? Not Until We Can Make a Superman or a Bionic Woman”
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May 26th, 2009 at 10:47 pm
Well said.
June 4th, 2009 at 11:48 pm
I want to thank you, Mead, for drawing attention to the urgent need to alleviate the burden of HIV and AIDS on the world. With HIV killing 5,500 people each day, the demand for an AIDS vaccine is palpable.
As you note, in the short-term, we must focus on expanding access to existing prevention methods to prevent as many people from becoming infected with HIV as possible. We must also continue to expand access to antiretroviral treatments and ensure that as many HIV-infected people as possible have access to these life-prolonging drugs. However, the fact remains that five people become newly infected with HIV for every two people put on antiretroviral treatment, and those lucky enough to have access to a lifetime of HIV treatment still won’t be cured of the disease. To mitigate and end the AIDS epidemic in the long-term, we need better prevention methods, including a vaccine. Historically, no other health intervention has been more cost effective or had a greater impact on public health than vaccination. An AIDS vaccine would also empower individuals, especially those who cannot control or negotiate the terms of sex and condom use, to protect themselves from one of the world’s deadliest diseases.
Admittedly, developing a vaccine for HIV has proven anything but easy. The virus is one of the toughest adversaries scientists have ever faced. But I’m encouraged by the advances mentioned in your blog, as well as by a steady stream of incremental advances in knowledge that have provided the foundation for AIDS vaccine development efforts now underway across the globe. We are working with Phil Johnson to advance the gene transfer of antibodies into humans. As importantly, new studies have recently led to finding many more exciting human broadly neutralizing antibodies. Furthermore, there are now a handful of products which look better in animals than the vaccine tested in the STEP trial that you refer to above. I am confident that these and other advances will give way to the development of better AIDS vaccine candidates for testing over the next few years. We have to trust in the power of science; our main task is to stay focused on this long term challenge.