Why the World Still Cannot Vaccinate Its Way Out of HIV, Herpes or the Flu

By: Opeyemi Samuel

Four decades after the identification of HIV, there is still no vaccine against it. Herpes simplex virus infects an estimated 3.7 billion people under the age of fifty, and no vaccine exists for that either. Influenza kills somewhere between 290,000 and 650,000 people in an ordinary year, and the vaccine that holds it back must be rebuilt from scratch every season because the previous formulation has stopped working.

These are not, for the most part, failures of funding or of effort. They are failures to solve a single biological problem that sits at the centre of modern vaccine science: a number of the world’s most damaging viruses have evolved to systematically neutralise the very immune responses that vaccines exist to provoke. A review article published in the European Journal of Pharmaceutical and Medical Research sets out to map that problem in full, and to draw out what it means for the vaccines now under development.

The review was written by Zainab Adenekan, a Georgia State University biologist whose work concerns the molecular mechanics of viral immune evasion. Her account is organised around two mechanisms which she presents as opposite ends of a single spectrum — what she frames as the difference between silence and shape-shifting.

The first is latency. Certain viruses can fall dormant inside the cells they infect, shutting down protein production so completely that the immune system is left with nothing to detect. Herpesviruses do this in nerve and immune cells; HIV does it in resting memory T cells. In each case, Adenekan explains, the viral genome survives intact while displaying no outward sign of its presence. A vaccine can train the immune system to recognise and destroy a cell that is actively producing virus, but it cannot reach one that is harbouring a silent genome and showing no evidence of infection. This, she notes, is why HIV’s latent reservoir — established within days of infection — has defeated every attempt at a cure.
The second mechanism is antigenic variation. RNA viruses such as influenza and hepatitis C mutate faster than the adaptive immune system can respond. Influenza’s surface proteins accumulate small changes until antibodies raised against earlier strains no longer recognise them; periodically, the virus reshuffles its genome with animal strains to produce an entirely novel surface protein against which no population holds immunity. Every influenza pandemic on record, from 1918 onward, began with such an event. HIV, Adenekan observes, takes the same principle further still, generating thousands of genetic variants within a single patient and outrunning any antibody response within weeks.

Much of the public conversation about vaccines, the review suggests, treats immune evasion as a technical footnote. Adenekan’s argument is that it is closer to the defining constraint on what vaccination can achieve — and that recognising it as such reframes the design problem itself.

The practical implications she traces are substantial. For HIV, the review follows the rise of broadly neutralising antibodies — rare responses directed at structural features the virus cannot alter without crippling itself — as a template for a new class of vaccine. For influenza, it examines universal-vaccine candidates that present the conserved stem of a key surface protein rather than its variable head. For SARS-CoV-2, it highlights a finding with broad relevance: although the Omicron variant’s mutations largely escaped antibody neutralisation, T-cell immunity held firm across variants, because T cells tend to target internal viral proteins that are far more constrained against mutation. Vaccines built around those conserved internal targets, the review suggests, could offer more durable protection across variants.

The review also surveys a widening therapeutic arsenal — combination antiretroviral therapy that closes off HIV’s escape routes simultaneously, checkpoint inhibitors under trial to reverse immune exhaustion in chronic hepatitis B, and the experimental “shock and kill” strategy that forces HIV out of dormancy so that primed immune cells can reach it. Each, Adenekan notes, was conceived not simply to attack a virus but to dismantle the specific evasion mechanism that virus depends upon.

What emerges, in her account, is a shift in the logic of vaccination itself. The traditional model — present a viral protein, raise antibodies, confer protection — works against viruses that hold still and do not hide. Against pathogens that do one or both, vaccine design becomes an exercise in anticipation: targeting the structures a virus cannot afford to change, priming the responses it cannot suppress, and, where needed, pairing vaccination with therapies that strip away its defences. The viruses, Adenekan writes, have had millions of years to refine their evasion playbook. The open question is whether the science can now read that playbook well enough to write a counter-strategy that holds.