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Developing a vaccine for HIV may be harder than researchers thought, according to a study published online in Nature. Just as the virus develops resistance to antiviral drugs, it also evolves to evade the human immune system on a population-wide level, the researchers report.
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Human Immunodeficiency Virus
Image: NIAID
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Previous studies have examined the interaction of viral evolution with the human immune system in single patients, finding that people with certain variants of human leukocyte antigen (HLA), a key recognition element in the human immune system, can better control the infection.
Those studies provided "a small window of what's going on," said Colm O'hUigin, who studies viral evolution at the National Cancer Institute in Frederick, Md., and was not involved in the research. "This take is different because it gave a longer-term [view]-- and that is that the HLA is beginning to shape the virus in the population."
The study examined the interaction of different HLA variants with the virus in nine cohorts of patients from around the world, totaling 2875 subjects. The researchers initially focused on HLA-B51, which is known to mitigate a patient's infection; in patients who carry it, however, the virus often develops an "escape mutation" which can get around HLA-B51's protective effects.
The researchers found the escape mutation in 96% of people infected with HIV who have HLA-B51. But in regions where HLAB51 was common, the escape mutation was common too, showing that the virus was evolving to circumvent the immune system. Examination of 13 other escape mutations showed the same pattern.
For example, explained study author Bruce Walker, director of the Ragon Institute for HIV research at Harvard, the Massachusetts Institute of Technology, and the Massachusetts General Hospital, HLA B51 is quite common in Japan. Correspondingly, the viral mutation related to HLA-B51 is also much more prevalent in infected people -- not just in those who are B51-positive, but in those who are B51-negative as well. "It basically becomes the dominant population virus," Walker said.
Since the virus can develop strategies to evade the human immune system, it is likely capable of doing the same to any vaccine. Consequently, said O'hUigin, a vaccine designed against viral epitopes that HLA recognizes "will be initially successful, perhaps, but the virus itself will adapt to the vaccination strategy and will begin to persist in forms that are evasive to the vaccine."
Walker stressed that the findings may not be as dire as they appear. "At first glance, you look at this and think, oh my God, this is bad," he said. "On the other hand, as the virus changes, this may expose other targets" for vaccines. Also, he noted, some regions of the virus mutate less, and if they do mutate, the virus becomes weaker, so it may be possible to identify and target those areas instead.
Overall, Walker said, the study underscores the necessity of tracking HIV not just in the US, but in populations worldwide. "It helps to explain why HIV is different in different parts of the world -- because it has to adapt to different parts of the world."
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