It’s another silver lining for drugmakers targeting HIV: Researchers have found promise in a combo of a Johnson & Johnson vaccine and a Gilead immune booster.
The data is preclinical at this point but promising enough for the scientists involved to be encouraged. The lead researcher called it a "base hit" rather than a home run, but said it was a platform for further study.
In their two-year study, a team led by scientists at Beth Israel Deaconess Medical Center (BIDMC) combined Janssen’s therapeutic vaccine Ad26/MVA and Gilead’s TLR7 agonist in rhesus monkeys infected with SIV, the monkey version of HIV.
The combo suppressed the virus better than either component alone and did a better job of holding off the virus after therapy was stopped. HIV levels tend to rebound after drugs are discontinued.
The study, published in Nature, used "set-point viral load"—the level seen after an acute HIV infection stabilizes—as its yardstick. That number was reduced 100-fold for animals in the combo group, reaching a level 50 times lower compared with the control arms.
Viral rebound was delayed 2.5-fold, from a median of 10 days for the monkeys given a sham treatment to 25 days in the combo group.
Potentially the most exciting result was that, for three of the nine monkeys in the combo group, viral loads at first rebounded after therapy was discontinued but later declined to undetectable levels.
"If all the animals' viral loads had been undetectable, that would have been a home run," said Dr. Dan Barouch, lead author of the study and director of the Center for Virology and Vaccine Research at BIDMC, in a statement. "But the fact that all animals showed a reduction in viral load and three out of nine were undetectable, that's a solid base hit. It's definitely something that we can work from."
Still, it is important to differentiate that the study was only part of a plan to identify a functional cure for HIV—long-term viral suppression without antiretroviral therapy—not to eradicate the virus or permanently cure HIV, said Barouch.
The key obstacle to an HIV cure is that the HIV viruses remain hidden in infected cells during drug therapy and could easily recover from a dormant state to become active again once the drugs stop.
"We reasoned that if we can activate the immune cells that might harbor the virus, then the vaccine-induced immune responses might perform better seeking them out and destroying them," said Barouch, who is also a professor of medicine at Harvard Medical School. Scientists believe strategies to draw the virus out of hiding would be the first step toward eradicating HIV from the human body.
Many companies and organizations have been stepping up their efforts to develop an effective HIV vaccine. Earlier this month, the NIH started a 5,400-patient Phase III trial in South Africa that will last until the end of 2020. Two investigational vaccines are included, one each from Sanofi Pasteur and GlaxoSmithKline.
In the meantime, the Scripps Research Institute has also teamed with China’s Yisheng Biopharma to test its HIV vaccine tech with the latter’s PIKA adjuvant. The University of Maryland, Texas Biomed, University of Massachusetts and Duke University are also participating in the HIV vaccine R&D effort.