Recently, the Merck pharmaceutical company reported that its experimental HIV vaccine raised the rate of HIV infection among people who got the trial vaccine. 

Yes, you read that right. It was worse than nothing. This vaccine was composed of a few HIV proteins strapped onto an adenovirus, which causes colds. Among people with good immunity to this common cold virus, about 80% of the population, it increased the chances of contracting HIV. 

The saddest part is that this is not surprising. 

Virologists have long been skeptical about the possibility of an effective HIV vaccine. HIV infects the very immune cells that you stimulate to defend your body against it. Stimulating these cells increases the rate at which HIV can infect those cells and the rate of HIV replication in these cells. Thus, an HIV vaccine can make it more likely that you’ll get AIDS, and you might get it sooner and worse than if you weren’t immunized. 

So far, no one has found the Holy Grail of HIV vaccines: a broad, neutralizing antibody. A broad antibody is one that attaches to many variants of the virus. Protecting against a single strain of HIV is darn-near worthless because HIV mutates so fast that pretty much everyone has their own, personal strain. Neutralizing antibodies cause the virus or virally infected cells to be killed. Beyond the inability to find antibodies that broadly react with the many, many strains of fast-mutating HIV, many antibodies, including most of those produced in other HIV-vaccine studies, are not neutralizing. 

Even in studies with monkeys challenged with simian immunodeficiency virus, we haven’t found a vaccine that produces neutralizing antibodies and protects well against a broad range of viral strains, and the few studies that do have promising results are confounded because the researchers often can’t explain why.

So why are we racing to human trials? 

First, money. If a safe and efficacious HIV vaccine is produced, people will line up, set their names down on waiting lists, and pay beaucoup bucks to be immunized against this certain-death virus. To the pharmaceutical company, the patents will be a gold mine. Sure, they’ll throw a few vials of vaccine to the African or Thai prostitutes in the name of public heath and as thanks for dying during the testing of the really dangerous vaccines, but that won’t eat into their oil-company-like profit margins. 

The pharmaceutical companies are so eager to find a vaccine that works, anything that works, that they’re willing to burn a few thousand African and Asian prostitutes to do it. Those populations are unlikely to sue for a variety of reasons, several of them being that they’re overseas, poor, and if the vaccine doesn’t works or backfires, dead. I remember one vaccine that was up for review before going to human trials a few years ago, and the vaccine itself was expected to infect 30% of the trial participants with HIV and kill them. That’s not a failure rate, meaning that the vaccine didn’t protect them against getting HIV from someone else. That’s a side effect of the vaccine: slow death. Is it ethical? They were planning to test in and ultimately give this vaccine to destitute prostitutes, the kind who can’t afford condoms. Without the vaccine, the HIV infection rate is 100%. The other 70% may have been protected. However, the trial may have gone like the Merck trial above, and the other 70% may have been at greater risk, too. 

Second, millions of lives. If anyone finds a vaccine that works, even partially, millions of lives can be saved, and the wildfire spread of infection can be slowed or stopped. 

Third, the absence of a really, really good model system to study vaccines for proof of concept before going to human trials. Yes, monkeys get SIV (simian immunodeficiency virus,) but many monkeys like sooty mangabeys tolerate high titers of the virus without getting sick, and they do it with some unknown immune function. They don’t make neutralizing antibodies, either. (1) They defend some other way, and we’re not sure how. 

Fourth, no better ideas. Scientists are working as hard as they can, as fast as they can, but HIV is still a highly evolved, diabolical pathogen. Its major antigens (virus bits that the immune system recognizes to figure out it’s a virus) mutate like mad, like internet viruses, to use a perfectly circular analogy. 

So there you have it: Merck was trying to find a vaccine to save its bottom line and thousands of lives in the absence of good pre-phase-I model system. It backfired on them. 

One other really sad thing: there are a lot of other trials out there using everything from naked DNA to canarypox vectors to the smallpox-vaccine virus. They might all have exactly the same problem: they make antibodies, but those antibodies don’t stop or slow the virus, and they might make the infection rate and disease course worse. 

 

TK Kenyon, Author of RABID: A Novel 

“[A] philosophical battle between science and religion … with four very subtle and intriguing central characters. This is a novel quite unlike most standard commercial fare, a genre-bending story–part thriller, part literary slapdown with dialogue as the weapon of choice.” –Booklist Starred Review 

 

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