The HIV vaccine study known as HVTN 505 was shut down on April 25 on the recommendation of an independent data and safety monitoring board (DSMB). The interim analysis found that that the vaccine did not prevent HIV infection or reduce the viral load of those who became infected.
The study enrolled 2,504 men who have sex with men and transgender persons who have sex with men, at 21 sites across the United States. Half received the scheduled vaccine and half a placebo or dummy shots. It began in 2009 and the final volunteer was enrolled in March of this year.
Earlier vaccine trials have not been able to prevent HIV infection but they have produced some clues on how a vaccine might help strengthen the human immune system to better control the infection.
Monkeys infected with SIV, the simian equivalent of HIV, have an immune system that controls their virus so well they live a normal lifespan without signs of disease. The hope was to develop a vaccine that could help humans do the same.
But when the DSMB looked at volunteers who had participated in HVTN 505 for at least 28 weeks – enough time to receive the scheduled three vaccinations and generate an immune response – it found 14 new HIV infections among those who received the vaccine and only 9 among those who received placebo.
Even more disturbing, there was no difference in the viral load of those who became infected. There was no immediate evidence that the vaccine had strengthened the immune system to better control the initial infection.
The DSMB recommended that all injections be stopped but participants continue to be monitored and evaluated. The National Institute of Allergy and Infectious Diseases (NIAID), which sponsored the study, moved to do so. Extending the study is likely to increase its cost far beyond the $75 million originally budgeted.
Researchers are left with the task of trying to figure out what happened. Thousands of blood samples were collected at various time points and stored. Now they will have to be analyzed to evaluate what, if any, immune response the vaccine stimulated. And the volunteers will continue to be followed, generating additional samples to be studied.
All of the vaccines that have been developed for other diseases work on the same general principle; they expose the person or animal to a weakened and controlled form of the virus to generate antibodies to the invader and prepare the immune system to respond more quickly and powerfully if and when they later face a natural exposure to the pathogen.
One curious thing about monkeys is that they appear to control SIV with just a low level of immune activation. In contrast, most humans exposed to HIV mount a massive immune response to the virus, which in turn feeds upon and infects the very CD4 cells that are key to the immune response to disease.
Could it be that the best way to control initial HIV infection is with a low level immune response rather than a large powerful response? If that is true, it would stand traditional vaccine development strategy on its head, and likely mean many more years searching for a vaccine for HIV.