
By MIKE MAGEE
In a 1996 JAMA editorial Nobel Laureate Joshua Lederberg MD wrote “Our fight with microbes is far from over …odds are tipped in their favor…they outnumber us a billion fold, and mutate a billion times more quickly…pitted against microbial genes, we humans mainly have our wits.”
Now three decades later, our scientists remain in a “battle of wits” with this amazing viral foe, but even without a vaccine, have maintained a slide edge for humanity. Experts recently confirmed that we are unlikely to have a vaccine bullet by 2030. And it’s not because we haven’t tried. There have been more than 250 official HIV vaccine trials, with fewer than 10 making it past the safety threshold to test efficacy – and the best performer only had a moderate success rate in triggering some immunity in 31%.
HIV is just a bad actor according to Professor Anna Durbin at the Bloomberg School of Public Health at Johns Hopkins. To start with, it embeds its chemistry in the host’s DNA genome, blurring the boundaries between “self” and “non-self.” Most of our successful vaccines focus in on a protein portion of the virus envelop or capsule. But the HIV virus has a “glycan shield” – a protein envelope that incorporates around 95 different sugar molecules which shield or disguise the viral protein from detection by our immune system. As one expert described it, “The immune system’s antibodies approach the virus and effectively see a blurry cloud of sugars rather than the vulnerable protein underneath.”
The second problem is the virus’s “sloppy gene duplication” is riddles with mutations. This yields dozens of different versions each with endless subtype variations. This is not typical disciplined viral behavior. Today’s measles viral genome for example is nearly identical to its late 20th century version.
And finally, HIV’s favorite target for invasion is the CD4 lymphocyte, otherwise known as the “Helper T-cell.” That happens to be the cellular key that unlocks our entire immune apparatus. This virus effectively decapitates the lead generals of our defensive force. And yet, we’re gaining on the virus. How have we done it?
First, by focusing on two “work-arounds” that trigger “passive immunity” without the help of our own immune machinery. Three decades ago, breakthrough discoveries first offered a glimmer of hope in the form of antiretroviral medications. With a variety of different combined therapy approaches, HIV/AIDS emerged as “no longer a death sentence,” but a chronic disease, like diabetes, that could be managed. In the modern era, this effective approach has spawned PrEP, or “Pre-exposure Prophylaxis,” – a preventive regimen for HIV negative individuals who are at risk of contracting HIV.
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