Reviving HIV vaccine research
Brendan Maher
Wednesday, 24 September 2008 16:20 UTC
Ruslan Medzhitov and Dan Littman say “Major gaps remain in the understanding of how HIV and retroviral infection in general is sensed by the innate immune system, and how this initial sensing is translated into the activation of adaptive immunity.” In a commentary for Nature, they discuss why they think better cooperation between immunologists studying adaptive immunity and vaccinologists working on HIV might help make up for 25 years of getting nowhere with traditional vaccine approaches. What do you think.
Updated 01 October 2008 21:28 UTC
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Replies
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Although I agree completely with Professors Ruslan Medzhitov and Dan Littman that the innate immune response to HIV is a compelling issue, as recent advance in the field has shown, I would argue that the guiding principle they proposed (‘a vaccine should mimic, as much as possible, the immune recognition events that happen during a natural infection with the same pathogen’) has been the leading cause to the failures in finding an HIV vaccine. This principle implies an assumption, which is that the human immune system will always provide an optimal solution to any pathogen infection. All a researcher needs to do is to find and replicate that solution. The human immune system has evolved in response to pathogen challenges, and may continue to evolve upon future pressures. However, not all answers provided by evolution may always be through altering or advancing the immune system. By assuming a vaccine to new challenges, such as HIV, can be sought with successful classical approaches mentioned by the authors, one has to accept an omnipotent view on the human adaptive immune system, i.e. no pathogens exert selective pressures upon human, which violates evolution theory, contradicts many experimental facts, and thus is flawed.
To my knowledge, over the past 25 years, HIV vaccine researchers have just completed nearly a full circle: from B-cell-based vaccine to T-cell-based vaccine, then back to B-cell study again and on to innate immunity. At every stage, people were trying in their best effort, to mimic the naturally occurring events of HIV infection, down to molecular level. Even though HIV neutralizing antibodies do occur naturally in the rare long-term non-progressors, the ‘mimicking’ has so far been unsuccessful. Furthermore, the overwhelming majority of HIV carriers eventually develop AIDS if the virus is not suppressed by drugs. Such a reality suggests that human immune system at current evolution stage may not be able to select an optimal solution to the HIV problem, which, I must emphasize, does not mean it cannot be selected with human knowledge. Rather than following nature’s examples, some novel approaches may be required to leapfrog to such a solution, which may be naturally marginalized or could never be reached by the human immune system.
Perhaps at the time of accumulated failures in finding an HIV vaccine, the most important question to ask ourselves is why we assumed a desirable answer to the HIV problem exists naturally.
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