HIV-1 CTL Vaccine: OH SHI-

Um, so like, you now how 'HIV-1 doesnt evolve' and stuff?

Well, um, apparently its figuring out how to become invisible to an entire branch of our immune system.

Adaptation of HIV-1 to human leukocyte antigen class I

Oh shi-

Okay, there are 'flags' on the surface of every cell of your body-- MHC Class I molecules. On these 'flags' are little bits of protein the cell is making, telling passing by immune cells everything is fine.

When a retrovirus infects a cell, its genome/genes are treated exactly like the host genome/genes, so bits of retrovirus proteins get put on these flags. To passing by immune cells, these flags are like a skull-and-crossbones, signaling that something has gone horribly wrong with the cell, and it needs to die.

Now, if you and I are infected with the exact same virus, our pirate flags might not look exactly the same. Depending on what MHC Class I genes we have, we present different proteins in our MHC I molecules. Your pirate flag might be red. My skull might have an eye-patch. My CTLs can see my flags, but it couldnt see yours. Your CTLs could see your pirate flags, but it couldnt see mine. Its good, but complicated, genetics and immunology.

In the case of HIV-1 infection, some peoples pirate flags REALLY piss off their CTLs. Because their CTLs get so worked up, HIV-1 infected cells are slaughtered, lowering viral loads, thus slowing progression to AIDS.

HIV-1 usually evolves around this to 'hide' from CTLs. Maybe it puts a sombrero on the skull so the CTLs think its a party boat. But while HIV-1 evolves ways to hide from cytotoxic T-cells, this escape comes at a fitness cost. So if the sombrero-pirate-flag-HIV is transmitted to someone with a different MHC type whos CTLs couldnt see that pirate flag in the first place, HIV-1 is going to take off the sombrero and regain fitness.

The Problem: HIV-1 is figuring out how to evade CTLs... while maintaining fitness.

Certain MHC I types are associated with better HIV/AIDS prognosis. If you have HLA-B*57, HLA-B*27, HLA-B*51, youre going to progress to AIDS slower. But this correlation is crumbling as HIV-1 evolves with us. For instance in Japan, more and more people who are B*51 negative are being infected with B*51 escape mutants. In 1983, 21%. Today, 70%.

Furthermore, HLA-B*51 does not protect against disease progression in Japanese subjects infected between 1997 and 2008, whereas HLA-B*51-positive haemophiliacs infected in 1983 had lower viraemia levels and higher CD4 counts than HLA-B*51-negative haemophiliacs...
... Moreover, the strong associations between certain HLA class molecules, such as HLA-B*57, HLA-B*27 and HLA-B*51, and slow disease progression may decline as the epidemic continues, particularly where these HLA alleles are highly prevalent, and where HIV transmission rates are high.

HIV-1 is picking our locks. If we dont shut this beast down ASAP, CTL vaccine strategies will be utterly useless.

The paper authors try to be more optimistic. Maybe a future HIV-1 vaccine will just need to be altered now and then to keep up with the virus, like influenza vaccines:

The induction of broad Gag-specific CD8+ T-cell responses may be a successful vaccine strategy, but such a vaccine will be most effective if tailored to the viral sequences prevailing, and thus may need to be modified periodically to keep pace with the evolving virus.

Ugh. This is pretty damn impressive for such a 'pathetic' mutator...