Is an HIV vaccine possible?


O my soul, do not aspire to immortal life, but exhaust the limits of the possible. Pindar (517–437 BCE), Ancient Greek lyric poet

In early 2023, the Phase III Mosaic trial to develop an HIV vaccine candidate is stopped and a multicentre study is started, mainly to assess its preventive efficacy. The vaccine had reached an advanced stage of clinical development, having passed Phase II safety and immunogenicity testing. It was not stopped because of any adverse or harmful reactions in the trial participants. It was stopped because no significant difference was found between the preventive efficacy of the HIV vaccine given to one group of patients and the placebo given to the other.

To avoid pessimism, we should take a constructive view of defeat. A number of HIV vaccine strategies have been tried since the late 1980s, but none have worked and all have been abandoned. Research must and will continue. Other HIV vaccine prototypes are currently in Phase I trials – where they are tested for safety in a small group of volunteers.

So why has an effective HIV vaccine not yet been developed? In 1989, it was predicted that the development phases would take no more than five years. But not at all. Thirty years of intensive, well-funded research have failed to produce an effective preventive vaccine. What is so special about HIV? Why is it possible with other viruses, but not with HIV?

Viruses should not be compared with each other. Many attempts to develop vaccines against other viruses have failed. Viruses are too different in structure and characteristics. The generic term «virus» oversimplifies the reasoning that follows. Success stories seem difficult to extrapolate.

There are many possible reasons for the difficulties with HIV. First, HIV’s cellular target is the immune system itself, its objective and hiding place. Second, the variability of HIV, both between different strains and within the infected individual, is immense. Vaccine design requires conserved, non-variable, exposed viral parts. Third, we lack an effective natural and antibody-mediated immune response to infection. Only one type of patient, the «elite controllers», can contain HIV to some extent, but none can eliminate it. Finally, although the list of difficulties is longer, there is no suitable animal model for testing that can be extrapolated to humans. I will not elaborate further.

Albert Camus began his philosophical essay The myth of Sisyphus (1942) by quoting the poet Pindar. Sisyphus is a figure from Greek mythology of outstanding intelligence and mischievousness. Zeus sent him to the underworld to punish him with pushing a heavy rock up the side of a mountain. Before the rock reached the top, it rolled downhill and Sisyphus had to start carrying the heavy load back uphill. The same immense and so far fruitless effort is being made in the search for a preventive HIV vaccine.

According to the latest data from UNAIDS (year 2021), there are three new HIV infections and one premature death from AIDS-related illness every minute worldwide. Around 40 million people have died from HIV to date. Surely you have met some of them. «O my soul, do not seek an HIV vaccine, but exhaust the limits of the possible».

© Mètode 2023 - 117. The legacy of the dinosaurs - Volume 2 (2023)
Professor of the Department of Genetics at the University of Valencia.