Preventing the Unpreventable: Part 2

After 30 years of research, billions of dollars in spending, and millions of lives lost, are we any closer to finding a vaccine for HIV? In Part II of Preventing the Unpreventable, Inside NOVA's video blog series on the search for an HIV vaccine, we find out why some AIDS researchers are optimistic about the future. (For more on why HIV is such a formidable opponent, check out Part I of this series).

Almost every day, scientists from around the world release new findings about the biological structure of the HIV virus and its various subspecies, clinical test results that confirm or dispute the direction of vaccine development, or creative new vaccine concepts for eliciting immune response. Progress is happening in real time. So, where are we now?

Getting a potential vaccine to clinical trial is costly, logistically difficult, time-consuming, and ethically fraught. To drive progress toward that goal, large-scale organizations such as the HIV Vaccine Trials Network, the International AIDS Vaccine Initiative, and the U.S. Military HIV Research ProgramNational Institutes of Health and the Indian Council of Medical Research to private foundations, organizations including government agencies, non-profits, philanthropic foundations, and pharmaceutical companies, are joining forces to share research findings and build a collective database of HIV knowledge, all aimed at preventing HIV infection.

As Dr. Lindsey Baden of Brigham and Women's Hospital in Boston points out, scientists working to create a safe and effective HIV vaccine take two approaches. "Conceptually, I see it as two tasks: how to bring about immune responses, and then how to optimize the immune responses," he said. The worldwide effort to build an effective vaccine allows groups of researchers to pursue a diverse array of methods that take one of these approaches, with the hope that one will eventually lead to success.

The only large-scale trial deemed successful to date was the Thai Trial, conducted by the Thailand Ministry of Public Health and coordinated by the U.S. Military HIV Research Program. A combination of the techniques used in previous failed trails, the study involved 16,000 HIV-negative men and women between the ages of 18 and 30 and showed that the chances of catching HIV were 31.2% less for those who had taken the vaccine than those who received the placebo. U.S. and Thai officials announced the findings of the seven-year study in fall 2009. The modest results also suggested that without a booster or follow-up vaccine dose, the vaccine's effectiveness lowered over time. However, the trial is universally deemed the first HIV vaccine trial success, an important step toward proving that an HIV vaccine could be possible.

In addition to the few large-scale double-blind studies there have been some other significant discoveries throughout the recent decade:

  • In 2006, an American man in his 40s was the first and only person to ever be cured of HIV. Now known as the "Berlin patient," the man received a bone marrow transplant from a donor who has a naturally occurring genetic mutation that renders his cells immune to almost all strains of HIV. The mutation prevents a molecule called CCR5 from appearing on the surface of cells. CCR5 acts as a kind of door for the virus. Since most HIV strains must bind to CCR5 to enter cells, the mutation bars the virus from entering. For a transplant like this one to be successful, however, a donor's marrow must match the patient's marrow AND the donor must express the genetic mutation, which is extremely rare. Thus, replicating the miracle of the "Berlin patient" is nearly impossible, particularly as common practice, as a bone marrow transplant is a very risky procedure. Yet the results do provide hope for potential discoveries involving other mutations that may prevent HIV infection and the prospect of gene therapy (the insertion, alteration, or removal of gene's within an individual's cells) as the key to the HIV vaccine.
  • In Kenya, Dr. Frank Plummer recently identified female sex workers who are effectively immune to HIV because of under-active immune systems, a discovery that disputes traditional theories of immune response. When a person becomes infected with HIV, the virus attacks the immune system, breaking it down and infecting the cells. Infected immune system cells replicate, spreading the disease throughout the body. Plummer believes that the secret to HIV prevention is making the immune system "sleepy"--or less active--so that the immune system does not actively promote the spread of the virus, ultimately preventing HIV from ever taking hold.
  • In addition to those genetically resistant to HIV, "elite controllers" are infected with HIV, but remain symptom-free for extended periods of time, if not for life; they often never progress to AIDS. Some scientists believe they can explain genetic differences between elite controllers and other HIV-infected patients, but researchers are still in the first stages of reproducing the HIV-resistance in those who do not express the genes naturally.

In the next post we will speak with some of the individuals directly involved with HIV vaccine trials.

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Lindsey R. Baden , M.D., is Director of Infectious Diseases, Dana-Farber Cancer Institute; Director of Clinical Research, Division Infectious Diseases, Brigham and Women's Hospital; and Assistant Professor of Medicine at Harvard Medical School.

Dan H. Barouch, M.D., Ph.D. is the Chief of the Division of Vaccine Research, Department of Medicine, Beth Israel Deaconess Medical Center; and an Associate Professor of Medicine at Harvard Medical School.

Ken Mayer M.D., is the Medical Research Director and co-chair of the Fenway Institute at Fenway Health.

This is Part Two in the four-part blog series Preventing the Unpreventable: The Search for the HIV Vaccine written by Devon Dickau, who interned at NOVA in the spring of 2011 before graduating from the Harvard Graduate School of Education's program in Technology, Innovation and Education.

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