I can think of at least two ‘worst nightmares’ for vaccine designers.
- Your vaccine looked super in animal models and such… but it turns out to be directly harmful to people. And not ‘some’ people. All people.
- Your vaccine actually does the opposite of what you want it to do– instead of preventing the disease, it makes people more prone to the disease.
That second one is a nightmare come to life for a group of HIV-1 scientists:
Extended follow-up confirms early vaccine-enhanced risk of HIV acquisition and demonstrates waning effect over time among participants in a randomized trial of recombinant adenovirus HIV vaccine (Step study)
The “Step Study” was an HIV-1 vaccine trial that was stopped in 2009, because it appeared that people in the *vaccine* arm of the study group were getting infected at a *higher* rate than the people in the placebo arm. For real.
This paper is an analysis of that data, and data infection rates 18 months after the study was stopped. They stratified their data by who had preexisting antibodies to the virus in the vaccine, Ad5, and for some reason, by whether or not the person was circumcised.
Right after the trial was stopped, these groups had the following hazard ratios vs placebo:
Uncircumcised, Ad5+: 4.18
Uncircumcised, Ad5-: 2.66
Circumcised, Ad5+: 1.98
Circumcised, Ad5-: 0.38
4.18 Holy freaking crap.
But heres the good news! *creepy Stepford Wife forced smile* Whatever the really, really bad effect of this vaccine was inducing, it fades with time!
After all follow-up, these groups had the following hazard ratios vs placebo:
Uncircumcised, Ad5+: 1.58
Uncircumcised, Ad5-: 2.35
Circumcised, Ad5+: 1.61
Circumcised, Ad5-: 0.97
Its obvious to even the most casual observer that stopping HIV-1, making an HIV-1 vaccine is really, really difficult. And because its so difficult, we are needing to try new things that have never been tried before, for any virus, or any other disease– like utilizing Ad5 vectors. When you are trying revolutionary, new approaches… sometimes there are disasters. When you are trying to fly to the moon, occasionally a shuttle blows up . *This* shuttle blew up with almost 2000 people on board. All we can do is try to learn everything we can from the disaster, so it never happens again.