..:. Cracking My Vainpot .:..

10 years ago, I started my PhD in HIV immunology.

My department in Oxford was best known for its study on T cells that go around the body killing virus-infected cells. We have McMichael, Rowland-Jones, Phillips, Townsend, Hill, Cerundolo, Goulder, Klenerman, Screaton, Price, Sewell, Gallimore, Gao, Xu...

There was such a concentration of talents that I had no doubt if anybody was gonna give the world an HIV vaccine, we were.

One of the quirks about immunologists is that they either "believe" in antibodies or T cells. It's like a chicken and egg thing. Antibodies rid of the virus directly, but cytotoxic T lymphocytes (CTL) stop the body from producing them.

In the beginning, HIV researchers trumpeted the role of neutralizing anti-HIV antibodies. That hype lasted until infection studies in monkeys revealed that HIV can mutate to escape antibody control in merely 2 days.

It was devastating.

So the pendulum swung towards T cell-control of the virus. People in my department were treated like rock stars when CTL were found to be responsible for containing the initial spike in viral load during the acute phase of HIV infection.

One of my bosses discovered that HIV can also mutate to escape from T cell control, but that was interpreted as evidence for the efficiency of CTL in forcing the virus to evolve.

Back in 1999, everyone was in this blind "vaccination" mode, trying to induce better, faster, bigger CTL responses against HIV. To be fair, we really were THAT good. The Oxford "prime-boost" vaccination regime took over the world. The tetramer technology that we helped Mark Davis pioneered was a real revolution.

We won tens of millions of research grants, testing a whole basket of vaccines in mice, in monkeys, in the UK and in Africa. Even I had a patent.

Not only were we gonna cure AIDS, we were also eradicating Melanoma, TB and Malaria.

All at the same time! 

But at the back of our (my) head, however, the elephant in the room has never disappeared.

Everyone infected with HIV amount antibody and T cell responses against HIV. Left untreated, 99% of them die with those HIV-specific antibodies and T cells.

You may ask, so where is the evidence that CTL can protect against HIV from establishing an infection?

It must be somewhere!

It must be... in those small % of "long-term exposed uninfected" African prostitutes who got HIV everyday but remain healthy?!

It must be... in those gay couples where only one partner is infected?!

They must have some special immune system.

They must have some special T cells.

They must have some special antibodies.

They must have!

...

20 years. We've been searching for those special protective immune correlates for more than 20 years.

But nothing.

Nothing.

Well almost nothing.

They've found a handful of super antibodies that HIV can't escape from. But they don't explain everything and we don't know how to design vaccines that induce them.

* * *

Every year, immunologists all over the world convene to discuss progress.

I gate-crashed the Keystone meeting on HIV and immunology in Colorado earlier this week. I even did a YMCA with the wife of NIH's AIDS Vaccine Program Director.

But seeing my personal heros still hammering away at the same old thing after ten twenty years is truly heart-breaking.

I've followed their work since I was 17. I'd wait outside their office just to talk to them between conference calls. I wanted to work for them so much I had to pretend otherwise and rejected their first offer. I'd do ANYTHING to get them on my CV.

I even let them bleed me for white cells.

Now? Some switched to another virus, another disease. Others used the same technique screening for the same T cells, just on a slightly different scale or on a slightly different patient cohort.

Details.

More details.

On why we failed.

We have to.

THEY have to.

It's HIV.