Defeating AIDS: MIT reveals new vaccination method that could kill HIV in just two shots

One major reason why it has been difficult to develop an effective HIV vaccine is that the virus mutates very rapidly, allowing it to evade the antibody response generated by vaccines.

Several years ago, MIT researchers showed that administering a series of escalating doses of an HIV vaccine over two weeks could help overcome a part of that challenge by generating larger quantities of neutralizing antibodies.

However, a fast multidose vaccine regimen is not practical for mass vaccination campaigns.

In a new study, the researchers have found that they can achieve a similar immune response with just two doses, given one week apart.

The first dose, which is much smaller, prepares the immune system to respond more powerfully to the second, larger dose.

New HIV vaccination

This study, which combined computational modeling and experiments in mice, used an HIV envelope protein as the vaccine.

A single-dose version of this vaccine is now in clinical trials, and the researchers hope to establish another study group that will receive the vaccine on a two-dose schedule.

“By bringing together the physical and life sciences, we shed light on some basic immunological questions that helped develop this two-dose schedule to mimic the multiple-dose regimen,” says Arup Chakraborty, the John M. Deutch Institute Professor at MIT and a member of MIT’s Institute for Medical Engineering and Science and the Ragon Institute of MIT, MGH, and Harvard University.

This approach may also generalize to vaccines for other diseases, Chakraborty notes.

Two shots to kill the virus

Each year, HIV infects more than 1 million people around the world, and some of those people do not have access to antiviral drugs.

An effective vaccine could prevent many of those infections. One promising vaccine now in clinical trials consists of an HIV protein called an envelope trimer and a nanoparticle called SMNP.

Irvine’s lab developed the nanoparticle, which acts as an adjuvant to help recruit a stronger B cell response to the vaccine.

Researchers administered this and other experimental vaccines as a single dose in clinical trials.

However, growing evidence shows that a series of doses is more effective at generating broadly neutralizing antibodies.

The researchers believe the seven-dose regimen is effective because it mimics the body’s response to virus exposure: As more viral proteins, or antigens, accumulate in the body, the immune system mounts a strong response.

In the new study, the MIT team investigated how this response develops and explored whether they could achieve the same effect using fewer vaccine doses.

The researchers began by comparing the effects of one, two, three, four, five, six, or seven doses, all given over 12 days.

They initially found that while three or more doses generated strong antibody responses, two did not.

However, by tweaking the dose intervals and ratios, the researchers discovered that giving 20 percent of the vaccine in the first dose and 80 percent in a second dose, seven days later, achieved just as good a response as the seven-dose schedule.

The researchers are now studying this vaccine strategy in a nonhuman primate model.

They are also working on specialized materials that can deliver the second dose over an extended period, which could further enhance the immune response.