My professor said something two days ago that shocked me: “I honestly don’t think we’ll ever see an effective vaccine for HIV/AIDS.”

Considering how much of an expert he is, that was pretty demoralizing.  And I don’t believe him; I can’t believe him.  Too much is at stake.

Yet to date we’ve spent billions of dollars, and we’re not much closer to a vaccine for AIDS.  All we’ve learned are several ways that don’t work.  Here’s why.

The general idea around vaccines is that they prime the immune system to respond to invasion rapidly and efficiently. So the smallpox vaccine makes your body quickly attack invading smallpox viruses, and so on.

A quick immune response is extremely important because it typically takes more than a week for your body to respond fully to infections, and by that point you may be dead or paralyzed, like with polio.

Vaccines have also typically been against parts of the virus that don’t change, like the envelope that coats viruses as they float around in the blood, waiting to infect new cells.

Both of those ideas fail with HIV. First, there has been not a single person who developed AIDS and then healed from it fully – to the point where there is no virus left in their body. This is in spite of the fact that someone infected with HIV does in fact launch a full scale immune attack on it.

So if our immune systems are incapable of defeating HIV, a vaccine won’t necessarily do anything. The body’s soldiers will start fighting sooner but still lose the war.

Additionally, it has been extremely difficult to develop a vaccine against the parts of HIV that have worked for other diseases. This is for several reasons.

First, HIV shields itself from being targeted by covering itself in proteins taken up from the cell that it grew out of. This is like having a cloaking device. And the part of HIV that is unique to it, the complex that attaches it to cells to allow invasion, is withdrawn until the last possible moment. That means it is nearly invisible to the body.

As if that weren’t enough, HIV mutates rapidly. Those mutations create changes in the structure of the virus so fast that the immune system simply can’t keep up. It launches antibodies that are targeted against one strain of the disease, wipes that one out, but another strain entirely simply replaces the previous one.

For these reasons and more, despite the billions of dollars spent on research, we have had only one vaccine so far that showed any efficacy at all, and even those moderately positive results may not actually mean anything.

The reason that it has been so unsuccessful is because our classical approach to vaccine development simply does not work for HIV.

That said, I believe we shouldn’t give up hope yet. There are additional targets for vaccine development that have yet to be tried, especially the tat gene and product. And there are exciting new methods of vaccine delivery and design that may allow better targeting and response.

We can’t give up. More than 25 million people are currently infected with HIV, and that number is only rising. The lives of millions of people depend on us finding an answer to this problem.

We will next consider and discuss the HIV tat gene, which is, I may naively believe, an exciting new approach to vaccine development.

The HIV/AIDS Vaccine:

A few weeks ago I was sitting in the basement of the biomedical research center at my school, just having made it through another fascinating class on pharmacology.  It was time for lunch, so I made for the exit, meeting my friend along the way.

“Hey,” she said.  “Did you hear about the new AIDS vaccine that actually works?”

I would soon hear more about it.

The vaccine was given to 8,197 people, and not given to 8,198, for a total of more than 16,000 in the trial.  Of those incredibly large numbers, 51 of the vaccinated people contracted HIV, while 74 of those not vaccinated did.

While small, that difference meant something.  It meant that those given the vaccine had a 31% lower risk of infection.  In my AIDS class, when the professor started discussing the vaccine briefly, I wrote in my notes in all caps, “FIRST EVER EFFECTIVE AIDS VACCINE!” and considered throwing a party.  It felt like one of those pivotal days, when things were changing.

Problems with the Vaccines

The professor, a world renowned expert on viruses, pointed out several concerns with the vaccine.  First, it did not confer additional protection to those who did catch HIV.  So if you get the shot, then contract HIV, the disease will proceed according to its usual pattern.  This is significant because you would expect the vaccine to confer some protection, even in those who do get infected.

Second, the vaccine was simply a merger of two other vaccines, both of which did not work by themselves.  Why would you expect combining them to work? asked the professor.

Finally, the numbers, while statistically significant, were only barely so.  If a few more vaccinated people had caught AIDS, or a few less non-vaccinated, then the entire study wouldn’t mean anything.

I disagreed with the professor on the first two points, most likely because I’m ignorant.

The key factor about HIV is that an immune response to it is not protective.  The fact is that an infected person has a tremendous immune response to HIV – just it isn’t ever enough to wipe the disease out, as it constantly mutates to avoid the body’s attack.

This constant mutation to avoid destruction occurs for one major reason.  HIV can lay dormant in cells, waiting for the chance to spring up.  Once infection is established, permanent clearance, and immune response, is generally impossible.  For instance, there is, shortly after initial infection, a major immune response, which almost removes the virus from the body entirely.

So an effective vaccine could prevent the virus from establishing the initial beachhead, so to speak, but not provide any benefits beyond that.
It’s also a generally accepted idea that effective vaccines can be combinations of targets.  This occurs on several levels: first, a good vaccine can stimulate both the T and B cell lines in the immune system, which have different requirements for activation.  And second, a good vaccine can target multiple parts of a virus, trying to overwhelm it.

The thinking I had then was that the HIV vaccine elicited a stronger initial response to infection that prevented the formation of a beachhead.  And once that beachhead was established, the typical pattern where HIV disregards the immune system’s response, took over.

Professor Right, Student Wrong

Unfortunately, the professor’s third point was ultimately true.  Recent news seems to throw doubt on the exact numbers and validity of the study, lowering an already small effect to the range where it is meaningless.

We’ll next cover what potential vaccination strategies for fighting HIV/AIDS are.

Dashed hopes

Less than half a century ago, we thought we had eliminated the threat of infectious diseases.

We are about to see “the virtual elimination of the infectious disease as an important factor in social life,” said Nobel Prize Winner, Frank Burnet, in 1962.

And there was great reason to be optimistic.

Conditions that killed and crippled only a generation ago were being defeated, one by one, as we created effective vaccines. The full list of conditions conquered by vaccinations is breathtaking; scourges like measles, mumps, polio suddenly lost their power.  And we had developed antibiotics that could seemingly wipe out any bacterial infection.  Never again would the Black Death or Plague return.

It was an amazing time, which culminated  with the complete eradication of Smallpox in 1979, one of the worst diseases to afflict man ever.  (Smallpox is highly contagious, kills 30% of those infects, and permanently scars those who survive).

Just one year later, things took a dramatic turn for the worse.

Keen eyed researchers noticed that weird diseases were starting to occur, mostly in gay men and intravenous drug users. Kaposi’s Sarcoma, which causes growth of multicolored tumors all over the body, for instance, was happening way too often. And Pneumocystis jiroveci, a rare fungal infection of the lungs, also started to show up much more often than expected.

These diseases, and others, are normally easily stopped by a healthy immune system. Something had clearly destroyed the body’s defense system of those people.

It was the rise of HIV/AIDs.

This monstrous disease has killed more than 25 million people since then. It’s extremely wide spread. In parts of Africa, more than 10% of people currently are infected for the disease. It’s wiped out decades of improvements in life-span for struggling African countries.  The graph of how long you could reasonably hope to live in Uganda, for instance, took a nosedive from which it hasn’t recovered.

Make no mistake – HIV spares no country: more than 50,000 people were infected with it in the USA this year.

An answer is desperately needed, yet none has yet to arise.

What is HIV?

HIV is a retrovirus that spreads through transmission of bodily fluids, whether blood, semen or vaginal. A retrovirus works by infecting a cell then invading the cell’s center and inserting itself into the DNA.  The cell then produces high levels of virus until it dies.

HIV infects the immune system and, over the course of several years, slowly destroys the body’s population of T-cells, which play a key role in regulating immune response as well as directly killing diseases.

HIV specifically cripples the CD4+ line of T cells, which are involved in coordinating and promoting your body’s defense system against diseases.

Normally, you have about 800-1500 of the CD4+ T cells in each cubic millimeter of blood. Over time, with HIV infection, your levels fall to 500, at which point diseases which are normally not dangerous can invade.  Even more serious problems, however, arise when levels reach 200 or lower.

In addition to those mentioned above, infections can include candida albicans, a fungus that forms railroad-like rings in your throat, cyptococcus, toxoplasmosa, histoplasmosa, and others.

Worse. With the rise of a large number of people with weak immune systems, otherwise dormant diseases like Tuberculosis have raised their head. By finding vulnerable hosts, they are much better able to develop resistance to our current treatments, meaning drugs stop working and more virulent forms arise.

Untreated HIV almost always causes death eventually. The weakened body is no longer able to fight off the simplest disease, and so is destroyed. Other complications of infection can include wasting, large loss of weight, and serious diarrhea. In 1/3 of AIDs cases, HIV infects the brain and causes some form of dementia.

Fighting HIV

The greatest minds have turned to fighting this pandemic, and progress has been rapid. Within several years of discovering the presence of HIV, we figured exactly what the structure of the virus is, and created the first drugs to fight it.

It has also been disappointing. While we have developed drug treatments to keep the disease in check, we still have no cure, and no vaccine.

Yet there is hope, and many areas for potential research. We will cover those over the next few posts, including what the recent HIV vaccine news means, and what potential targets of HIV for future treatment are.