Future is Bright, But Progress is Slow for HIV Vaccine

Plans for an HIV vaccine, which could be used to inoculate high-risk populations against the virus, are almost three decades in the making, and doctors around the world continue to test a variety of new products. While time is ticking away, with more than 2 million new infections annually, progress has been slow, and it will likely be several more years before any vaccines are commercially available.

The path to create a vaccine has been rife with setbacks, including a 2007 trial of a vaccine produced by Merck, which appeared to make recipients increasingly susceptible to the virus. Two years later there was news of a more successful clinical trial in Thailand called RV144, which was sponsored by the Surgeon General of the United States Army and was found to reduce HIV infections by 31 percent. While the improvement was incremental, it gave the scientific community hope.

"If we want to try to continue to make this vaccine work better, people may need to get additional booster shots, since it seems to wear off over time," noted Colonel Nelson Michael, director of the U.S. Military HIV Research Program at the Walter Reed Army Institute of Research, of the RV144 trial. Michael pointed out that the study had a higher efficacy rate the first year, but that ability to prevent infection declined over time.

Michael has been active in convincing pharmaceutical companies Novartis and Sanofi Pasteur to collaborate on helping to produce future testing of variants of RV144, which had originally combined ALVAC-HIV by Sanofi, an inert canary pox virus genetically engineered with three HIV genes, and AIDSVAX, a genetically engineered HIV surface protein made by Genentech.

The upcoming vaccine study, slated for 2015 and 2016, will not use AIDSVAX, but will instead use a product made by Novartis. The trials will be completed with help from the Bill and Melinda Gates Foundation, the Pox Protein Public Private Partnership, the National Institute of Allergy and Infectious Diseases and the HIV Vaccine Trials Network.

Demand to participate in this study is high, especially in regions were the disease is rampant. Michael noted that while there have been no shortage of volunteers in Thailand or South Africa, there are incidences in which women apply to enroll in studies but withdraw when their partners don't support the idea.

Even if the tests are successful, Michael doesn't anticipate a vaccine becoming widely available until 2021, as pharmaceutical manufacturers have been cautious about ramping up production of a vaccine, and are waiting to see efficacy above 50 percent.

"The future has never been brighter for HIV vaccines," said Michael, "but it will likely take eight more years."

One challenge in creating a successful vaccine is that HIV is a constantly mutating virus, with different strains developing and occurring in varied populations throughout the world.

"You are actually making a vaccine against a swarm of viruses," said Wayne Koff, chief scientific officer of the International AIDS Vaccine Initiative. "It is different in Africa, in China, in Thailand and in the United States." He adds that one of the reasons it is impossible to use a live attenuated HIV virus in a vaccine is it can mutate and become more virulent.

Because of the challenge to create a single vaccine for HIV, other research instead focuses on helping the body develop broadly neutralizing antibodies that latch on to regions of the virus and make it incapable of infecting healthy cells.

A study published in the Journal of Nature Medicine in October cited research on these types of antibodies from the Centre for AIDS Programme of Research in South Africa. The study followed two HIV-positive women for several years, and discovered a key change in the outer coating of the HIV virus, which allowed them to antibodies that could fight a large variety of HIV strains.

"This research is still in a very early stage," said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, which helped fund the study. "We can't even begin to predict how long it will take to commercially produce a vaccine using this research."

Finally, a different type of vaccine was tested in March at Western University's Schulich School of Medicine & Dentistry and funded by Sumagen Canada, a subsidiary of Korean-based pharmaceutical venture company, Sumagen Co. Ltd. It uses a genetically deactivated whole virus. The vaccine, called SAV001-H, seemed to boost the immunity of patients who were already infected with HIV, without major side effects.

But most laboratories have avoided pursuing this type of vaccine because it carries significant risk with it, due to the chance that it could actually spread the disease, not prevent it.

"There is the possibility that you won't kill the whole virus, and you have to be very careful with a potentially lethal disease," Fauci noted.

But Dr. Chil-Yong Kang, who led the study in Canada, said that preliminary tests were very encouraging. "Our results suggest it's safe and we have deleted the gene noted for pathogenesis," said Kang, who will next try the vaccine on 600 HIV-negative volunteers who are high-risk for the infection, including commercial sex workers, men who have sex with men and intravenous drug users. A third round of testing would include an even larger sample of high-risk, HIV-negative volunteers.

Despite any potential consequences of this type of vaccine, demand is high for this product. "We are inundated with requests from people who want to volunteer," said Kang.